Diastereoselective process for preparing n-substituted amino aci

Details Diastereoselective process for preparing n-substituted amino aci Diastereoselective process for preparing n-substituted amino aci

1992-10-06

1994-03-08

Brust, Joseph P.

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

Organic compounds

Nitriles

558348, 558350, 558351, 558390, 558441, C07C25330

Patent

active

052929183

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND

Diastereoisomeric amino acids and derivatives are useful intermediates for preparing various pharmaceutical compounds such as enkephalinase inhibitors which are useful for treating pain or as inhibitors of the angiotensin converting enzyme (ACE) which are useful for treating hypertension or reducing elevated intraocular pressure associated with glaucoma. U.S. Pat. No. 4,652,668 discloses a process for preparing a class of pharmaceuticals useful in inhibiting angiotensin converting enzyme in humans such as N-(1-(S)-ethoxycarbonyl-3-phenylpropyl)-L-proline maleate salt is representative. German Offenlegungsschrift DE 3624376 A1 discloses a process for preparing 0-Acyl-glycosyl amines derivatives useful for preparing amino acids and derivatives by first treating an aldehyde compound with 0-acyl glycosyl amine under acidic conditions, followed by treatment with trimethylsilyl or sodium cyanide and tin or zinc (tetra)-chloride in tetrahydrofuran, isopropanol or chloroform. P. K. Subramanian and R. W. Woodward, Synth. Commun. 16 (3), pp. 337-342 (1986) disclose a four-step asymmetric Strecker synthesis for preparing (R)-(+)-2-methyl-3-phenylalanine by utilizing (S) phenylalanine as the chiral auxiliary reagent. K. Weinges, G. Graab, D. Nagel and B. Stemmle, Chem. Ber. Vol. 104 , pp. 3594-3606 (1971) disclose an external asymmetric Strecker synthesis of .alpha.-methyl-amino acids. K. Weinges, K. Gries, B. Stemmle, W. Schrank, Chem. Ber. Vol. 110, pp. 2098-2105 (1977) disclose an asymmetric Strecker synthesis with (S)-(-)-1-phenylethylamine as a chiral handle to afford stereochemically homogeneous .alpha.-methyl-.alpha.-aminonitriles. K. Weinges and B. Stemmle, Chem. Ber. Vol. 106, pp. 2291-2297 (1973) disclose an asymmetric Strecker synthesis of aliphatic .alpha.-methyl-.alpha.-amino acids. S. Inoue et al. J. Chem. Soc. Chem. Comm. 1981, pp. 229. Japan Kokai Tokkyo Koho, JP 01047754 A2 Feb. 22, 1989 Heisei, JP 87-204860 Aug. 18, 1987, CA111(13):114878h discloses a process for preparing .gamma.-1-carboxyethylamino-.gamma.-phenylbutyronitrile and .gamma.-phenylbutyric acid derivatives as intermediates for anti-hypertensive compounds. The article of K. Kawashiro, S. Morimoto and H. Yoshida, Gas chromatography-mass spectrometry of trimethylsilylated imino derivatives of alanine, Bull. Chem. Soc. Jpn., 58(7), pp. 1903-12 discloses trimethylsilylation of seven imino derivatives of alanine with N,O-bis(trimethylsilyl)trifluoracetamide in acetonitrile. It would be desirable to provide a process for preparing either (S,S) or (R,R) diastereoisomers in high optical yields which is relatively inexpensive and which does not require a protecting group for the amine starting material.


SUMMARY OF THE INVENTION

The present invention is directed to a process for preparing an (S,S) or (R,R) diastereoisomer of the formula: ##STR2## or salts, esters or amides thereof, wherein R.sup.3 and R.sup.4 independently represent hydrogen, alkyl, aryl or aryl substituted with halogen, alkyl, nitro or alkoxy, and n and m independently represent integers from one to six, comprising combining a cyanide compound of the formula: added proton source, a solvent and a Lewis acid of the formula: with an optically active .alpha.-amino acid compound of formula (I): ##STR3## or salts, esters or amides thereof, wherein R.sup.3 and m are as defined hereinbefore, followed by addition of an acyl or acetal compound of the formula (II): ##STR4## wherein m, n and R.sup.4 are as defined hereinbefore, R.sup.1 is hydrogen, alkyl or phenyl and R.sup.2 and R.sup.3 independently represent alkyl or cycloalkyl, to give the diastereoisomer of formula (X).
The present invention has the advantage of preparing diastereoisomers of formula (X). That is, either the (S,S) or the (R,R) diastereoisomer can be prepared by selection of the desired optically active .alpha.-amino acid (I) beforehand. The present process advantageously uses as few or fewer steps than other processes previously taught. The present process has the further advantage of utilizing relatively

REFERENCES:
patent: 4551537 (1985-11-01), Mai et al.
patent: 4652668 (1987-03-01), Kim
P. K. Subramanian and R. W. Woodward, Synth. Commun. 16(3), pp. 337-342 (1986).
K. Weinges, G. Graab, D. Nagel and B. Stemmle, Chem. Ber. vol. 104 pp. 3594-3606 (1971).
K. Weinges, K. Gries, B. Stemmle, W. Schrank, Chem., Ber. vol. 110 pp. 2098-2105 (1977).
K. Weinges and B. Stemmle, Chem. Ber. vol. 106, pp. 2291-2297 (1973).
K. Kawashiro, S. Morimoto and H. Yoshida, Bull. Chem., Soc. Jpn, 58(7), pp. 1903-1912 (1985).
C.A. 111: 114878h, Inoue, et al., (1989), vol. 111.

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