Optically active aminoalcohol derivatives and method of producin

Details Optically active aminoalcohol derivatives and method of producin Optically active aminoalcohol derivatives and method of producin

1995-06-21

1997-04-01

Haley, Jacqueline

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

560 23, 564186, C07C21528

Patent

active

056167261

DESCRIPTION:

BRIEF SUMMARY
This application is a National Stage application of PCT/JP94/01049 filed Jun. 29, 1994 and published as WO 95/01323 on Jan. 12, 1995.


TECHNICAL FIELD

The present invention relates to 3-amino-1-nitro-4-phenyl-2-butanol derivatives of the general formula (1) shown below and a method of producing 3-amino-2-hydroxy-4-phenylbutyric acid derivatives of the general formula (11) shown below. An optically active isomer of 3-amino-2-hydroxy-4-phenylbutyric acid (hereinafter referred to as phenylnorstatine) obtainable from a compound of general formula (11) serves as a starting compound for the synthesis of the immunopotentiating anticancer agent bestatin [formula (12)] [Journal of Antibiotics, 29, 600 (1976)] and for the synthesis of the HIV protease inhibitor KNI-227 [formula (13)] (Japanese Kokai Publication Hei-5-170722). Therefore, the compounds provided by the present invention are useful as intermediates of medicinal chemicals. ##STR2##
In the above formulas, R.sup.1 and R.sup.2 each independently represents a hydrogen atom or an amino group protecting group, R.sup.3 represents a hydrogen atom or a hydroxy group protecting group and R.sup.6 represents a hydrogen atom or an alkyl group containing 1 to 6 carbon atoms. ##STR3##


BACKGROUND ART

Phenylnorstatine of the formula (14) ##STR4## includes four optically active isomers. Among them, the one that can serve as a bestatin intermediate is the (2S,3R)-threo form and the one that can serve as a constituent of KNI- 227 is the (2S,3S)-erythro form. Therefore, a technique of selectively producing only one optical isomer is required for the production of such forms:by a commercially valuable method.
Several methods are known for the stereoselective production of the bestatin intermediate (2S,3R)-phenyl norstatin. Typical of them are those processes that comprise stereoselective addition of a cyanide compound to an (R)-2-amino-3-phenylpropanal derivative derived from D-phenylalanine [Journal of the Chemical Society Chemical Communications, 938 (1989); Synthesis, 703 (1989); European Patent Specification No. 341462; Japanese Kokai Publication Hei-2-17165]. From the industrial viewpoint, however, these processes pose a problem in that the use of a highly toxic cyanide compound is inevitable.
Other methods known include the process comprising degradation of an optically active 2-azetidone derivative obtained via [2+2] cycloaddition of a chiral imine and a ketene compound [Tetrahedron Letters, 31, 3031 (1990)], and the process comprising stereoselective alkylation and stereoselective amination of a chiral glyoxylate [Journal of Organic Chemistry, 54, 4235 (1989)]. However, these methods involve a number of steps, hence are complicated from the procedural viewpoint.
Further methods known comprise stereoselectively alkylating a malic acid ester, selectively amidating one of the carboxyl groups and subjecting the amidation product to Curtius type rearrangement to give optically active phenylnorstatine [European Patent Specification No. 379288; Tetrahedron Letters, 33, 6803 (1992)]. These methods, however, use lithium hexamethyldisilazane, which is an expensive base, and a toxic lead compound, among others, hence are not suited for commercial production.
On the other hand, few methods are known for the stereoselective production of (2S,3S)-phenylnorstatine derivatives. A technique is known which comprises erythro-selective addition of trimethylsilylcyanide to (S)-2-dibenzylamino-3-phenylpropanal in the presence of a Lewis acid [Tetrahedron Letters, 29, 3295 (1988)]. It appears possible to synthesize (2S,3S)-phenylnorstatine by applying this technique. However, the use of a toxic cyanide compound is inevitable in this case, too, and it is difficult to deprotect the dibenzyl protective group.
Another conceivable process making use of the above-mentioned method of selectively synthesizing (2S,3R)-phenylnorstatine derivatives might comprise selectively synthesizing the (2R,3S) form and inverting the configuration of the position 2 by tile per se known method [Journal of the

REFERENCES:
patent: 5475138 (1995-12-01), Pal et al.

Affiliated with

Also associated with

Rating

Optically active aminoalcohol derivatives and method of producin does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Optically active aminoalcohol derivatives and method of producin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Optically active aminoalcohol derivatives and method of producin will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-540216