Optically active nitro alcohol derivatives, optically active amino alcohol derivatives, and process for producing thereof

Abstract

Optically active 1-substituted phenyl-2-nitro alcohol derivatives having the formula (1) and the process for producing thereof, and 1-substituted phenyl-2-amino alcohol derivatives having the formula (2) and the process for producing thereof from the optically active 1-substituted phenyl-2-nitro alcohol derivatives. From these nitro alcohols, pharmaceuticals such as (R)-albutamin and (R)-sarmeterol useful as a bronchodilator is obtained via optically active amino alcohols which are useful pharmaceutical intermediates.

1 - 30 . (canceled)  
   
   
       31 . A process for producing an optically active 1-substituted phenyl-2-amino alcohol derivative of the following formula (14)  
     
       
         
         
             
             
         
       
     
     in which n and m represent positive integers satisfying 0<n+m≦5; R 1  and R 2  represent a hydrogen atom or a hydroxyl-protective group, respectively and when n+m is 2 or more, R 1  and R 2  are independent of each other or form a ring among R 1 s, among R 2 s, and among R 1 (s) and R 2 (s); R 3  represents —(CH 2 ) l — in which l is 0, 1, 2 or 3; R 4  represents a hydrogen atom, an alkyl group, or a hydroxymethyl group, 
 which comprises stereoselectively reducing an optically active 1-substituted phenyl-2-nitro alcohol derivative of the following formula (1)  
                     
 in which n and m represent positive integers satisfying 0<n+m≦5; R 1  and R 2  represent a hydrogen atom or a hydroxyl-protective group, respectively, and when n+m is 2 or more, R 1  and R 2  are independent of each other or form a ring among R 1 s, among R 2 s, and among R 1 (s) and R 2 (s); R 3  represents —(CH 2 ) l — in which l is 0, 1, 2 or 3; R 4  represents a hydrogen atom, an alkyl group, or a hydroxymethyl group; and * represents an optically active site, and when R 4  is a hydrogen atom, optical activity at the site to which R 4  is added is lost and * is omitted.  
 
   
   
       32 . A process for producing an optically active 1-(3,4-dihydroxyphenyl)-2-amino alcohol derivative of the following formula (14-1)  
     
       
         
         
             
             
         
       
     
     in which R 5  and R 6  represent a hydrogen atom or a hydroxyl-protective group, respectively, and they are independent of each other or form a ring: R 4  represents a hydrogen atom, an alkyl group, or a hydroxymethyl group, 
 which comprises stereoselectively reducing an optically active 1-(3,4-dihydroxyphenyl)-2-nitro alcohol derivative of the following formula (1-1)  
                     
 in which R 5  and R 6  represent a hydrogen atom or a hydroxyl-protective group, respectively, and they are independent of each other or form a ring; R 4  represents a hydrogen atom, an alkyl group, or a hydroxymethyl group; and * represents an optically active site, and when R 4  is a hydrogen atom, optical activity at the site to which R 4  is added is lost and * is omitted.  
 
   
   
       33 . A process for producing (R)-albutamin having the following formula (15),  
     
       
         
         
             
             
         
       
     
     characterized in that the (R)-1-(3,4-dihydroxyphenyl)-2-amino alcohol derivative of the following formula (14-2)  
     
       
         
         
             
             
         
       
     
     is used as a raw material which is obtained by reducing the (R)-1-(3,4-dihydroxyphenyl)-2-nitro alcohol derivative of the following formula (1-5).  
     
       
         
         
             
             
         
       
     
   
   
       34 . A process for producing (R)-sarmeterol having the following formula (16),  
     
       
         
         
             
             
         
       
     
     characterized in that the (R)-1-(3-hydroxymethyl-4-hydroxyphenyl)-2-amino alcohol derivative of the following formula (14-3)  
     
       
         
         
             
             
         
       
     
     is used as a raw material which is obtained by reducing the (R)-1-(3-hydroxymethyl-4-hydroxyphenyl)-2-nitro alcohol derivative of the following formula (1-6).