T-butoxycarbonylaminoethylamine for the Synthesis of PNA Monomer Units, Amino Acid Derivatives, Intermediates Thereof, and Processes for Productions of Them

Abstract

A process for amino acid derivatives shown by the below general formula (I): (wherein R 1 means a hydrogen atom or a straight chain or branched chain alkyl group with 1-5 carbon atoms.) having an object to provide a process of the amino acid derivatives of the formula (I) and their synthetic intermediate, t-butoxycarbonylamino-ethylamine, whereby it requires no tedious procedure and is also good in yield, and its application to a mass production is easy, and to provide novel amino acid derivatives of the formula (IV), their synthetic intermediates, and a process thereof, characterized in that it comprises a step to obtain the amino acid derivatives shown by the general formula (I) by hydrolysis of compounds shown by the below formula (II): (wherein R 1 has the same meaning as described above, and R 2 means a straight chain or branched chain alkyl group with 1-4 carbon atoms.) as well as amino acid derivatives shown by the general formula (IV): (wherein R 1 means a hydrogen atom or a straight chain or branched chain alkyl group with 1-5 carbon atoms, and n means any one of integers 1-11.), and a process for the amino acid derivative, characterized in that it comprises a reduction step of benzyloxycarbonyl-ω-amino acid derivatives.

1 .- 5 . (canceled) 
     
     
         6 . A process comprising a step to obtain compounds shown by the general formula (V): 
       
         
           
           
               
               
           
         
       
       by hydrolysis of the compounds shown by the general formula (VI): 
       
         
           
           
               
               
           
         
       
       wherein R 1  means a hydrogen atom or a straight chain or branched chain alkyl group with 1-5 carbon atoms, and n means any one of integers 1-11 and R 2  means a straight chain or branched chain alkyl group with 1-4 Carbon atoms. 
     
     
         7 . The process according to  claim 6 , wherein the hydrolysis of the compounds shown by the general formula (VI) is carried out by an aqueous alkaline mmetal hydroxide solution. 
     
     
         8 . The process according to  claim 7 , further comprising a step in which alkaline metal ion is removed by cation-exchange chromatography using pyridinium ion as a counter ion. 
     
     
         9 . The process according to  claim 7 , wherein the alkaline metal is selected from the group consisting of lithium, sodium and potassium. 
     
     
         10 . The process according to  claim 6 , further comprising the step of obtaining the compounds shown by the general formula (VI) by the reaction of benzyloxycarbonyl-ω-amino acids shown by the general formula (VII) below: 
       
         
           
           
               
               
           
         
       
       wherein n means any one of integers 1-11 and the compounds shown by the general formula (II): 
       
         
           
           
               
               
           
         
       
       wherein R 1  means a hydrogen atom or a straight chain or branched chain alkyl group with 1-5 carbon atoms, and R 2  means a straight chain or branched chain alkyl group with 1-4 carbon atoms. 
     
     
         11 - 12 . (canceled) 
     
     
         13 . The process according to  claim 10 , wherein the compounds shown by the general formula (II) are obtained by reaction of t-butoxycarbonylamine prepared from ethylenediamine and a compound shown by the general formula (III) 
       
         
           
           
               
               
           
         
       
       wherein R 1  means a hydrogen atom or a straight chain or branched chain alkyl group with 1-5 carbon atoms, R 2  means a straight chain or branched chain alkyl group with 1-4 carbon atoms, and n means any one of integers 1-11 . 
     
     
         14 . The process for the compounds shown by the general formula (V): 
       
         
           
           
               
               
           
         
       
       wherein R 1  means a hydrogen atom or a straight chain branched chain alkyl group with 1-5 carbon atoms, R 2  means a straight chain or branched chain alkyl group with 1-4 carbon atoms, and n means an integer of 1-11) comprising the step of obtaining the compounds shown by the general formula (V) by hydrolysis of the compounds shown by the general formula (VI): 
       
         
           
           
               
               
           
         
       
       wherein R 1  means a hydrogen atom or a straight chain or branched chain alkyl group with 1-5 carbon atoms, R 2  means a straight chain or branched chain alkyl group with 1-4 carbon atoms, and n means any one of integers 1-11. 
     
     
         15 . The process for the compounds shown by the general formula (VI): 
       
         
           
           
               
               
           
         
       
       wherein R 1  means a hydrogen atom or a straight chain or branched chain alkyl group with 1-5 carbon atoms, R 2  means a straight chain or branched chain alkyl group with 1-4 carbon atoms, and n means an integer of 1-11, comprising the step of obtaining the compounds shown by the general formula (VI) by reaction of benzyloxycarbontl-ω-amino acid shown by the general formula (VII): 
       
         
           
           
               
               
           
         
       
       wherein n means any one of integers 1-11 and a compound of the general formula (II): 
       
         
           
           
               
               
           
         
       
       wherein R 1  means a hydrogen atom or a straight chain or branched chain alkyl group with 1-5 carbon atoms, and R 2 means a straight chain or branched chain alkyl group with  1-4 carbon atoms. 
     
     
         16 - 18 . (canceled)