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