Amino alcohol derivative and method for preparing the same

• US 5,907,039 A
• Filed: 12/09/1996
• Issued: 05/25/1999
• Est. Priority Date: 12/08/1995
• Status: Expired due to Term

• Current Assignee: Seikagaku Kogyo Kabushiki Kaisha
• Original Assignee: Seikagaku Kogyo Kabushiki Kaisha
• Inventors: Inokuchi, Jinichi, Oyamada, Hidekazu, Jinbo, Masayuki
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): Rao, Deepak R.
• Application Number:
  US08/761,934
• Time in Patent Office: 897 Days
• Field of Search: 540/609, 546/246, 546/247, 548/566, 548/567, 548/569, 548/950, 548/967
• US Class Current: 540/609
• CPC Class Codes: C07B 53/00 Asymmetric syntheses
• CPC Class Codes: C07C 215/18 with hydroxy groups and at least two amino groups bound to the carbon skeleton
• CPC Class Codes: C07C 231/02 from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
• CPC Class Codes: C07C 231/18 by stereospecific synthesis
• CPC Class Codes: C07C 233/36 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07D 207/08 with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 211/22 by oxygen atoms
• CPC Class Codes: C07D 211/44 attached in position 4
• CPC Class Codes: C07D 295/125 with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/13 to an acyclic saturated chain

Abstract

Amino alcohol derivatives with a primary amino group or a substituted amino group influence the synthesis of glycolipids and have antiviral, antitumor, metastasis inhibiting and neural cell growth enhancing functions. The amino alcohol derivatives are useful in preparing 2-acylamino alcohol derivatives.

Claims

1. An amino alcohol derivative represented by the following formula (2):

space="preserve" listing-type="equation">R.sup.2 --CH.sub.2 --(C*)H(HNP.sup.1)--(C*)H(OH)--R.sup.1 (

     2)

wherein

C* is an asymmetric carbon atom;

P¹ is an amino-protecting group selected from the group consisting of benzvloxycarbonyl groups which may have at least one substituent, alkoxycarbonyl groups which may have at least one substituent, and a benzenesulfonyl group;

R¹ is an alkyl group, a cycloalkyl group or an aryl group; and

R² is ##STR5## wherein R⁵ is a hydrogen atom or at least one substituent, and if two or more said substituents, said substituents are the same or different, wherein said substituent is a hydroxyl group, a lower alkyl group, a lower alkoxyl group, a hydroxyl-lower-alkyl group, a carboxyl group, a (lower alkoxyl) carbonyl group, an aralkyl group, a piperidino group, an acyloxy group, an amino group or an amino-lower-alkyl group; and

m is an integer of 2 to 6.

2. The amino alcohol derivative according to claim 1, wherein

R¹ is an alkyl group or a cycloalkyl group, or a phenyl group which may be substituted with from 1 to 3 substituents which are the same or different and are selected from a lower alkyl group, a lower alkoxyl group, a hydroxyl group, a hydroxyl-lower-alkyl group and a nitro group;

and

P¹ is an amino-protecting group selected from (i) a benzyloxycarbonyl group which may be substituted with a nitro group, a halogen atom, a lower alkoxyl group, a (lower alkoxyl)phenylazo group or a phenylazo group and (ii) an alkoxycarbonyl group having a straight, branched or cyclic alkyl group which may be substituted with a fluorenyl group or a methylsulfonyl group.

3. The amino alcohol derivative according to claim 1, wherein

R¹ is an alkyl group having from 6 to 15 carbon atoms, a cyclohexyl group or a phenyl group;

P¹ is an amino-protecting group selected from a benzyloxycarbonyl group, a t-butoxycarbonyl group and an octyloxycarbonyl group; and

R² is an amino group selected from a pyrrolidino group which may be substituted with a hydroxyl group or a hydroxyl-lower-alkyl group or a piperidino group which may be substituted with a hydroxyl group or a hydroxyl-lower-alkyl group.

4. The amino alcohol derivative according to claim 1, wherein

R¹ is a phenyl group;

P¹ is a benzyloxycarbonyl group; and

R² is a pyrrolidino group, a hydroxypyrrolidino group or a hydroxypiperidino group; and

the configuration of said derivative is (1S,2S).

5. The amino alcohol derivative according to claim 1, wherein

R¹ is a phenyl group;

P¹ is a benzyloxycarbonyl group; and

R² is a pyrrolidino group or a piperidino group; and

the configuration of said derivative is (1R,2R).

6. A process for preparing the amino alcohol derivative defined in any one of claims 1 to 5 which comprises the steps:

(A) reacting an aminopropanol derivative represented by formula (1);

space="preserve" listing-type="equation">Y--CH.sub.2 --(C*)H(NHP.sup.1)--(C*)H(OH)--R.sup.1 (

     1)

wherein

C* is an asymmetric carbon atom;

P¹ is an amino-protecting group selected from the group consisting of benzyloxycarbonyl groups which may have at least one substituent, alkoxycarbonyl groups which may have at least one substituent, and a benzenesulfonyl group;

R¹ is an alkyl group, a cycloalkyl group or an aryl group; and

Y is a leaving group, with an amine represented by R² H, wherein

R² is ##STR6## wherein R⁵ is a hydrogen atom or at least one substituent, and if two or more said substituents, said substituents are the same or different, wherein said substituent is a hydroxyl group, a lower alkyl group, a lower alkoxyl group, a hydroxyl-lower-alkyl group, a carboxyl group, a (lower alkoxyl) carbonyl group, an aralkyl group, a piperidino group, an acyloxy group, an amino group or an amino-lower-alkyl group; and

m is an integer of 2 to 6;

to obtain an amino alcohol derivative represented by formula (2);

space="preserve" listing-type="equation">R.sup.2 --CH.sub.2 --(C*)H(NHP.sup.1)--(C*)H(OH)--R.sup.1 (

     2)

wherein P¹, R¹ and R² each has the same meaning as defined above.