Original scientific paper

On the Way to α-Methyl-α-amino Acids; Unusual Elimination-addition in 3,3-Disubstituted 1,4-Benzodiazepin-2-ones and Inversion of Enantioselectivity in the Lipase Catalyzed Acetylation

Amir Avdagić ; Ruđer Bošković Institute, P. O. Box 180, Bijenička 54, HR-10002 Zagreb, Croatia
Vitomir Šunjić ; Ruđer Bošković Institute, P. O. Box 180, Bijenička 54, HR-10002 Zagreb, Croatia

Abstract

(−)-3 -Methanesulfoxymethyl-3-acetoxoymethyl-7-chloro-5-phenyl-1,4-benzodiazepin-2-one, (−)-2, reacts with ethanethiol in the presence of a strong base affording racemic elimination-addition product 3-ethylthiomethyl-7-chloro-5-phenyl-1,4-benzodiazepin-2-one (4). In-termediary 3-methylene-7-chloro-5-phenyl-1,4-benzodiazepin-2-one (3) is formed by pericyclic C−C bond breaking during elimination of both acyloxy groups. The second approach to α-methyl-α-amino acids comprises kinetic resolution of racemic 3-hydroxymethyl-3-benzyl-7-chloro-5-phenyl-1,4-benzodiazepin-2-one (7) via acetylation by Novozym 435 lipase; enantiomeric excess (e.e.) for alcohol (3S)-(+)-7 33.2%; e.e. for acetate (3R)-(−)-8 30.2%. Opposite direction of enantio-selectivity during acetylation of 7 and the recently studied 9 (Ref. 3) was established by determination of absolute conformation and rela-tive configuration at C(3) (pseudoaxial/pseudoequatorial) by com-bining CD and 1H NMR spectroscopy.

Keywords

1,4-Benzodiazepin-2-ones; kinetic resolution; absolute configuration

Hrčak ID:

132013

URI

https://hrcak.srce.hr/132013

Publication date:

4.9.2000.

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