14-membered ketolides and methods of their preparation and use

Abstract

Provided herein are methods of preparing new 14-membered ketolides via coupling of an eastern and western half moiety, followed by macrocyclization, and optional functionalization. Intermediates in the synthesis of these ketolides including the eastern and western halves are also provided. Pharmaceutical compositions and methods of treating infectious diseases and inflammatory conditions using these ketolides are also provided.

1 - 67 . (canceled) 
     
     
         68 . A compound of Formula (N-1a), (N-1c), or (N-1d): 
       
         
           
           
               
               
           
         
       
       or a salt thereof; wherein
 R 2a  and R 2b  are independently hydrogen, halogen, carbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or wherein R 2a  and R 2b  are taken together to form 
 
       
         
           
           
               
               
           
         
         each of R o1  and R o2  is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         L 3  is a group of formula: 
       
       
         
           
           
               
               
           
         
            represents a single or double bond; 
         R 3  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)R Z8 , —C(═O)OR Z8 , —C(═O)N(R Z8 ) 2 , an oxygen protecting group, or a group of formula: 
       
       
         
           
           
               
               
           
         
         R 4  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         each instance of R 18  and R 19  independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         each instance of R 20  and R 21  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, halogen, or carbonyl, or R 20  and R 21  are joined to form an optionally substituted cyclopropyl or an oxiranyl ring; 
         each instance of R 5a  and R 5b  is independently hydrogen, halogen, silyl, optionally substituted alkyl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl; 
         R 9  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)R Z8 , —C(═O)OR Z8 , —C(═O)N(R Z8 ) 2 , an oxygen protecting group, or a carbohydrate; 
         each instance of L C1  and L C2  is independently a bond, or a linking group selected from the group consisting of optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene; optionally substituted heteroalkylene, optionally substituted heteroalkenylene, optionally substituted heteroalkynylene, optionally substituted carbocyclylene, optionally substituted heterocyclylene, and combinations thereof; 
         each instance of A 1  is independently a leaving group (LG), —SH, —OH, —NH 2 , —NH—NH 2 , —N 3 , —O—NH 2 , —C(═O)R X1 , 
       
       
         
           
           
               
               
           
         
         A is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —NH—, —NH—NH—, —NH—O—, —O—NH—, —S—, 
       
       
         
           
           
               
               
           
         
         Q is —NH—, —NH—NH—, —O—NH—, —NH—O—, —S—, or —O—; 
         W is O, S, or NR W1 ; 
         R W1  is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a nitrogen protecting group; 
         R W2  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R W2  groups are joined to form an optionally substituted cyclic moiety; 
         R X1  is hydrogen, halogen, or —OR X2 , wherein R X2  is hydrogen, optionally substituted alkyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; 
         R 23  is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         each instance of R Z8  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R Z8  groups are joined to form an optionally substituted heterocyclyl or optionally substituted heteroaryl ring; 
         R s1  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         G 2  is a group of formula: 
       
       
         
           
           
               
               
           
         
       
       wherein:
 R 6  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, carbonyl, silyl, or halogen; 
 each instance of R 15  is independently silyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; and 
 each instance of R 16a  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
 
       
         
           
           
               
               
           
         
       
       or a salt thereof: wherein R 2a , R 2b , R 5a , R 5b , R 9 , L 3 , and G 2  are as defined for Formula (N-1a);
 R 1a  is hydrogen, halogen, carbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
 G 3  is —O—, —S—, or —N(R G1 )—, wherein R G1  is hydrogen, optionally substituted alkyl, or a nitrogen protecting group; 
 R 7  and R 8  are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
 R s8  is hydrogen or —OR 11 ; 
 R 11  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; 
 R no  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; and 
 P 1  is hydrogen, silyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen, nitrogen, or thiol protecting group; 
 
       
         
           
           
               
               
           
         
       
       or a salt thereof: wherein P 1 , G 3 , R s8 , R 1a , R 8 , and R 7  are as defined for Formula (N-1c); and R 2a , R 2b , R 5a , R 5b , R 9 , L 3 , and G 2  are as defined for Formula (N-1a). 
     
     
         69 - 70 . (canceled) 
     
     
         71 . A method of preparing a compound of Formula (N-7): 
       
         
           
           
               
               
           
         
       
       or a salt thereof;
 the method comprising coupling a compound of Formula (N-1a): 
 
       
         
           
           
               
               
           
         
       
       or a salt thereof, with a compound of Formula (N-1b); 
       
         
           
           
               
               
           
         
       
       or a salt thereof, to give a compound of Formula (N-1c): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein;
 Z is of formula: 
 
       
         
           
           
               
               
           
         
         each instance of R 1a , R 1b , R 2a , and R 2b  is independently hydrogen, halogen, carbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or wherein R 1a  and R 1b  or R 2a  and R 2b  are taken together to form 
       
       
         
           
           
               
               
           
         
         a indicates the point of attachment to the carbon substituted by G 1 ; 
         b indicates the point of attachment to L 3 ; 
         each of R o1  and R o2  is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         R no  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; 
         R sa  is hydrogen, hydrogen, halogen, carbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         or R sa  and R 1a  or R sa  and R 1b  are taken together to form a bond; 
         R s8  is hydrogen or —OR 11 ; 
         L 3  is a group of formula: 
       
       
         
           
           
               
               
           
         
            represents a single or double bond; 
         R 3  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)R Z8 , —C(═O)OR Z8 , —C(═O)N(R Z8 ) 2 , an oxygen protecting group, or a group of formula: 
       
       
         
           
           
               
               
           
         
         R 4  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         each instance of R 18  and R 19  independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         each instance of R 20  and R 21  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, halogen, or carbonyl, or R 20  and R 21  are joined to form an optionally substituted cyclopropyl or an oxiranyl ring; 
         each instance of R 5a  and R 5b  is independently hydrogen, halogen, silyl, optionally substituted alkyl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl; 
         R Y1  is —OR 17 , and R Y2  is hydrogen, or R Y1  is halogen, and R Y2  is hydrogen, or R yl  is halogen, and R Y2  is halogen, or R Y1  and R Y2  are joined to form an oxo (═O) group; 
         R 6  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, carbonyl, silyl, or halogen; 
         R 7  and R 8  are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         R 9  and R 17  are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)R Z8 , —C(═O)OR Z8 , —C(═O)N(R Z8 ) 2 , an oxygen protecting group, or a carbohydrate; 
         R 10  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, carbonyl, silyl, or halogen; 
         G 3  is —O—, —S—, or —N(R G1 )—, wherein R G1  is hydrogen, optionally substituted alkyl, or a nitrogen protecting group; 
         G 1  is hydrogen, —OR 12 , or —NR 13 R 14 ; 
         provided when G 1  is —OR 12 , then R 11  and R 12  are joined as a group of formula —C(═O)— to provide a cyclic carbonate: or R 11  and R 12  are not joined, and R 11  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; and R 12  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group, or a group of formula; 
       
       
         
           
           
               
               
           
         
         or provided when G 1  is —NR 13 R 14 , then R 11  and R 13  are joined as a group of formula —C(═O)— to provide a cyclic carbamate, or R 11  and R 13  are not joined, R 11  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group, and R 13  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; 
         R 14  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group, —C(═O)R Z8 , —C(═O)OR Z8 , or a group of formula: 
       
       
         
           
           
               
               
           
         
         or R 13  and R 14  are joined to form an optionally substituted heterocyclyl or optionally substituted heteroaryl; 
         each instance of L C1  and L C2  is independently a bond, or a linking group selected from the group consisting of optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene; optionally substituted heteroalkylene, optionally substituted heteroalkenylene, optionally substituted heteroalkynylene, optionally substituted carbocyclylene, optionally substituted heterocyclylene, and combinations thereof; 
         each instance of A 1  is independently a leaving group (LG), —SH, —OH, —NH 2 , —NH—NH 2 , —N 3 , —O—NH 2 , —C(═O)R X1 , 
       
       
         
           
           
               
               
           
         
         A is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —NH—, —NH—NH—, —NH—O—, —O—NH—, —S—, —O— 
       
       
         
           
           
               
               
           
         
         Q is —NH—, —NH—NH—, —O—NH—, —NH—O—, —S—, or —O—; 
         W is O, S, or NR W1 ; 
         R W1  is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a nitrogen protecting group; 
         R W2  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R W2  groups are joined to form an optionally substituted cyclic moiety; 
         R X1  is hydrogen, halogen, or —OR X2 , wherein R X2  is hydrogen, optionally substituted alkyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; 
         R 23  is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         each instance of R Z8  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R Z8  groups are joined to form an optionally substituted heterocyclyl or optionally substituted heteroaryl ring; 
         R s1  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         Y 1  is 
       
       
         
           
           
               
               
           
         
         LG is a leaving group capable of being displaced by a nucleophile; 
         P 1  is hydrogen, silyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen, nitrogen, or thiol protecting group; and 
         G 2  is a group of formula: 
       
       
         
           
           
               
               
           
         
       
       wherein:
 each instance of X G2  is —OR 15 , —SR 15 , or —N(R 15 ) 2 ; 
 each instance of R 15  is independently silyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or two R 15  groups are taken together to form an optionally substituted heteroaryl or heterocyclic ring; and 
 each instance of R 16a  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. 
 
     
     
         72 . The method of  claim 71  further comprising oxidizing, and optionally protecting a compound of Formula (N-1c): 
       
         
           
           
               
               
           
         
       
       or a salt thereof;
 to provide a compound of Formula (N-1d); 
 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         73 . The method of  claim 72  further comprising protecting a compound of Formula (N-1d-a): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, followed by an intramolecular nucleophilic addition to provide a compound of Formula (N-1e): 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         74 . The method of  claim 73  further comprising reacting a compound of Formula (N-1e) 
       
         
           
           
               
               
           
         
       
       or a salt thereof, with a nucleophile to provide a compound of Formula (N-1f): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein
 R o3  is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, —OR n1 , —SR n1 , or —N(R n1 ) 2 ; 
 R o4  is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, or optionally substituted heteroaryl; and 
 each instance of R n1  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen, a sulfur protecting group when attached to a sulfur, or a nitrogen protecting group when attached to nitrogen. 
 
     
     
         75 . The method of  claim 73  further comprising reducing and optionally protecting a compound of Formula (N-1e): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, to provide a compound of Formula (N-1f): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein
 each of R o3  and R o4  is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, —OR n1 , —SR n1 , or —N(R n1 ) 2 ; and 
 each instance of R n1  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen, a sulfur protecting group when attached to a sulfur, or a nitrogen protecting group when attached to nitrogen. 
 
     
     
         76 . The method of  claim 75  further comprising cyclizing a compound of Formula (N-1f): 
       
         
           
           
               
               
           
         
       
       or a salt thereof; 
       to give a compound of Formula (N-1g): 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         77 . The method of  claim 76  further comprising reacting a compound of Formula (N-1g) with an alkylating agent, R 10 -LG, or a halogenating agent to provide a compound of Formula (N-1h): 
       
         
           
           
               
               
           
         
       
       or a salt thereof; wherein R 10  is halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl;
 LG is a leaving group; 
 each of R o3  and R o4  is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, —OR n1 , —SR n1 , or —N(R n1 ) 2 ; and 
 each instance of R n1  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen, a sulfur protecting group when attached to a sulfur, or a nitrogen protecting group when attached to nitrogen. 
 
     
     
         78 . The method of  claim 72 , further comprising cyclizing a compound of Formula (N-1d): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, to provide a compound of Formula (N-2-C); 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         79 . The method of  claim 78 , further comprising protecting a compound of Formula (N-1i): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, followed by an intramolecular nucleophilic addition to provide a compound of Formula (N-1j); 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         80 . The method of  claim 79 , further comprising reacting a compound of Formula (N-1j): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, with a nucleophile to provide a compound of Formula (N-1k): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein;
 each of R o3  and R o4  is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, —OR n1 , —SR n1 , or —N(R n1 ) 2 ; and 
 each instance of R n1  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen, a sulfur protecting group when attached to a sulfur, or a nitrogen protecting group when attached to nitrogen. 
 
     
     
         81 . The method of  claim 79 , further comprising reducing a compound of Formula (N-1j): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, to provide a compound of Formula (N-1k): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein
 each of R o3  and R o4  is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, —OR n1 , —SR n1 , or —N(R n1 ) 2 ; and 
 each instance of R n1  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to an oxygen, a sulfur protecting group when attached to a sulfur, or a nitrogen protecting group when attached to nitrogen. 
 
     
     
         82 . A method of preparing a compound of Formula (N-7): 
       
         
           
           
               
               
           
         
       
       or a salt thereof;
 the method comprising coupling a compound of Formula (N-1m): 
 
       
         
           
           
               
               
           
         
       
       or a salt thereof, with a compound of Formula (N-1n); 
       
         
           
           
               
               
           
         
       
       or a salt thereof, to give a compound of Formula (N-1d): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein:
 Z is of the formula (z-i) or (z-ii); 
 
       
         
           
           
               
               
           
         
         each instance of R 1a , R 1b , R 2a , and R 2b  is independently hydrogen, halogen, carbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or wherein R 1a  and R 1b  or R 2a  and R 2b  are taken together to form 
       
       
         
           
           
               
               
           
         
         a indicates the point of attachment to the carbon substituted by G 1 ; 
         b indicates the point of attachment to L 3 ; 
         each of R o1  and R o2  is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         R no  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; 
         R sa  is hydrogen, hydrogen, halogen, carbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         or R sa  and R 1a  or R sa  and R 1b  are taken together to form a bond; 
         R s8  is hydrogen or —OR 11 ; 
         L 3  is a group of formula: 
       
       
         
           
           
               
               
           
         
            represents a single or double bond; 
         R 3  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)R Z8 , —C(═O)OR Z8 , —C(═O)N(R Z8 ) 2 , an oxygen protecting group, or a group of formula: 
       
       
         
           
           
               
               
           
         
         R 4  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         each instance of R 18  and R 19  independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         each instance of R 20  and R 21  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, halogen, or carbonyl, or R 20  and R 21  are joined to form an optionally substituted cyclopropyl or an oxiranyl ring; 
         each instance of R 5a  and R 5b  is independently hydrogen, halogen, silyl, optionally substituted alkyl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl; 
         R Y1  is —OR 17  and R Y2  is hydrogen, or R Y1  is halogen and R Y2  is hydrogen, or R Y1  is halogen and R Y2  is halogen, or R Y1  and R Y2  are joined to form an oxo (═O) group; 
         R 6  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, carbonyl, silyl, or halogen; 
         R 7  and R 8  are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         R 9  and R 17  are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)R Z8 , —C(═O)OR Z8 , —C(═O)N(R Z8 ) 2 , an oxygen protecting group, or a carbohydrate; 
         R 10  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, carbonyl, silyl, or halogen; 
         G 3  is —O—, —S—, or —N(R G1 )—, wherein R G1  is hydrogen, optionally substituted alkyl, or a nitrogen protecting group; 
         G 1  is hydrogen, —OR 12 , or —NR 13 R 14 ; 
         provided when G 1  is —OR 12 , then R 11  and R 12  are joined as a group of formula —C(═O)— to provide a cyclic carbonate, or R 11  and R 12  are not joined, and R 11  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group, and R 12  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group, or a group of formula; 
       
       
         
           
           
               
               
           
         
         or provided when G 1  is —NR 13 R 14 , then R 11  and R 13  are joined as a group of formula —C(═O)— to provide a cyclic carbamate, or R 11  and R 13  are not joined, R 11  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group, and R 13  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; 
         R 14  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group, —C(═O)R Z8 , —C(═O)OR Z8 , or a group of formula: 
       
       
         
           
           
               
               
           
         
         or R 13  and R 14  are joined to form an optionally substituted heterocyclyl or optionally substituted heteroaryl; 
         each instance of L C1  and L C2  is independently a bond, or a linking group selected from the group consisting of optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene; optionally substituted heteroalkylene, optionally substituted heteroalkenylene, optionally substituted heteroalkynylene, optionally substituted carbocyclylene, optionally substituted heterocyclylene, and combinations thereof; 
         each instance of A 1  is independently a leaving group (LG), —SH, —OH, —NH 2 , —NH—NH 2 , —N 3 , —O—NH 2 ,
 —(═O)R X1   
 
       
       
         
           
           
               
               
           
         
         A is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —NH—, —NH—NH—, —NH—O—, —O—NH—, —S—, —O—, 
       
       
         
           
           
               
               
           
         
         Q is —NH—, —NH—NH—, —O—NH—, —NH—O—, —S—, or —O—; 
         W is O, S, or NR W1 ; 
         R W1  is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a nitrogen protecting group; 
         R W2  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R W2  groups are joined to form an optionally substituted cyclic moiety; 
         R X1  is hydrogen, halogen, or —OR X2 , wherein R X2  is hydrogen; optionally substituted alkyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; 
         R 23  is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; and 
         each instance of R Z8  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R Z8  groups are joined to form an optionally substituted heterocyclyl or optionally substituted heteroaryl ring; 
         Y 2  is —C(═O)—CH═P(R P1 )(R P2 )(R P3 ) or —C(═O)—CH 2 —P(O)(OR P2 )(OR P3 ), 
         each of R P1 , R P2 , and R P3  is independently optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocycyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         P 1  is hydrogen, silyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen, nitrogen, or thiol protecting group; and 
         G 2  is a group of formula: 
       
       
         
           
           
               
               
           
         
       
       wherein;
 each instance of X G2  is —OR 15 , —SR 15 , or —N(R 15 ) 2 ; 
 each instance of R 15  is independently silyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or two R 15  groups are taken together to form an optionally substituted heteroaryl or heterocyclic ring; and 
 each instance of R 16a  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl. 
 
     
     
         83 . The method of  claim 82 , further comprising halogenating a compound of Formula (N-4): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, to provide a compound of Formula (N-7a): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein X is a halogen. 
     
     
         84 . The method of  claim 82 , further comprising treating a compound of Formula (N-2): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, with an alkylating agent, R 10 -LG, or a halogenating agent to provide a compound of Formula (N-3): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein R 10  is halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl. 
     
     
         85 . The method of  claim 82 , further comprising halogenating a compound of Formula (N-3): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, to provide a compound of Formula (N-6b): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein each instance of X is independently a halogen. 
     
     
         86 . A method of preparing a compound of Formula (N-3): 
       
         
           
           
               
               
           
         
       
       or a salt thereof;
 the method comprising cyclizing a compound of Formula (N-1o): 
 
       
         
           
           
               
               
           
         
       
       or a salt thereof; 
       wherein;
 Z is of formula: 
 
       
         
           
           
               
               
           
         
         each instance of R 1a , R 1b , R 2a , and R 2b  is independently hydrogen, halogen, carbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or wherein R 1a  and R 1b  or R 2a  and R 2b  are taken together to form 
       
       
         
           
           
               
               
           
         
         a indicates the point of attachment to the carbon substituted by G 1 ; 
         b indicates the point of attachment to L 3 ; 
         each of R o1  and R o2  is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         R no  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; 
         R sa  is hydrogen, hydrogen, halogen, carbonyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl: or R sa  and R 1a  or R sa  and R 1b  are taken together to form a bond; 
         R s8  is hydrogen or —OR 11 ; 
         L 3  is a group of formula: 
       
       
         
           
           
               
               
           
         
            represents a single or double bond; 
         R 3  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)R Z8 , —C(═O)OR Z8 , —C(═O)N(R Z8 ) 2 , an oxygen protecting group, or a group of formula: 
       
       
         
           
           
               
               
           
         
         R 4  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         each instance of R 18  and R 19  independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         each instance of R 20  and R 21  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, halogen, or carbonyl, or R 20  and R 21  are joined to form an optionally substituted cyclopropyl or an oxiranyl ring; 
         each instance of R 5a  and R 5b  is independently hydrogen, halogen, silyl, optionally substituted alkyl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl; 
         R 6  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, carbonyl, silyl, or halogen; 
         R 7  and R 8  are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; 
         R 9  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)R Z8 , —C(═O)OR Z8 , —C(═O)N(R Z8 ) 2 , an oxygen protecting group, or a carbohydrate; 
         R 10  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, substituted amino, carbonyl, silyl, or halogen; 
         G 3  is —O—, —S—, or —N(R G1 )—, wherein R G1  is hydrogen, optionally substituted alkyl, or a nitrogen protecting group; 
         G 1  is hydrogen, —OR 12 , or —NR 13 R 14 ; 
         provided when G 1  is —OR 12 , then R 11  and R 12  are joined as a group of formula —C(═O)— to provide a cyclic carbonate, or R 11  and R 12  are not joined, and R 11  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group, and R 12  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group, or a group of formula; 
       
       
         
           
           
               
               
           
         
         or provided when G 1  is —NR 13 R 14 , then R 11  and R 13  are joined as a group of formula —C(═O)— to provide a cyclic carbamate, or R 11  and R 13  are not joined, R 11  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group, and R 13  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; 
         R 14  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group, —C(═O)R Z8 , or —C(═O)OR Z8 , or a group of formula: 
       
       
         
           
           
               
               
           
         
         or R 13  and R 14  are joined to form an optionally substituted heterocyclyl or optionally substituted heteroaryl; 
         each instance of L C1  and L C2  is independently a bond, or a linking group selected from the group consisting of optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene; optionally substituted heteroalkylene, optionally substituted heteroalkenylene, optionally substituted heteroalkynylene, optionally substituted carbocyclylene, optionally substituted heterocyclylene, and combinations thereof; 
         each instance of A 1  is independently a leaving group (LG), —SH, —OH, —NH 2 , —NH—NH 2 , —N 3 , —O—NH 2 , —C(═O)R X1 , 
       
       
         
           
           
               
               
           
         
         A is optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —NH—, —NH—NH—, —NH—O—, —O—NH—, —S—, —O—, 
       
       
         
           
           
               
               
           
         
         Q is —NH—, —NH—NH—, —O—NH—, —NH—O—, —S—, or —O—; 
         W is O, S, or NR W1 ; 
         R W1  is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a nitrogen protecting group; 
         R W2  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R W2  groups are joined to form an optionally substituted cyclic moiety; 
         R X1  is hydrogen, halogen, or —OR X2 , wherein R X2  is hydrogen, optionally substituted alkyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group; 
         R 23  is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl; and 
         each instance of R Z8  is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R Z8  groups are joined to form an optionally substituted heterocyclyl or optionally substituted heteroaryl ring; 
         P 1  is hydrogen, silyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen, nitrogen, or thiol protecting group; and 
         G 2  is a group of formula; 
       
       
         
           
           
               
               
           
         
         each instance of X G2  is —OR 15 , —SR 15 , or —N(R 15 ) 2 ; and 
         each instance of R 15  is independently silyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or two R 15  groups are taken together to form an optionally substituted heteroaryl or heterocyclic ring. 
       
     
     
         87 . The method of  claim 86 , further comprising reducing, and optionally protecting, a compound of Formula (N-3): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, to provide a compound of Formula (N-5): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein R 17  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)R Z8 , —C(═O)OR Z8 , —C(═O)N(R Z8 ) 2 , an oxygen protecting group, or a carbohydrate. 
     
     
         88 . The method of  claim 87 , further comprising halogenating a compound of Formula (N-5): 
       
         
           
           
               
               
           
         
       
       or a salt thereof, to provide a compound of Formula (N-7b); 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein X is a halogen. 
     
     
         89 - 94 . (canceled) 
     
     
         95 . The method of  claim 71 , wherein each of L C1  and L C2  is independently of one of the following formulae; 
       
         
           
           
               
               
           
         
       
       wherein each instance of p is 0, 1, or 2. 
     
     
         96 - 100 . (canceled)