On the way to alpha-methyl-alpha-amino acids; Unusual elimination-addition in 3,3-disubstituted 1,4-benzodiazepin-2-ones and inversion of enantioselectivity in the lipase catalyzed acetylation

Avdagić, Amir; Šunjić, Vitomir (2000) On the way to alpha-methyl-alpha-amino acids; Unusual elimination-addition in 3,3-disubstituted 1,4-benzodiazepin-2-ones and inversion of enantioselectivity in the lipase catalyzed acetylation. Croatica Chemica Acta, 73 (3). pp. 743-753. ISSN 0011-1643

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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). Intermediary 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 a-methyl-cl-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 enantioselectivity during acetylation of 7 and the recently studied 9 (Ref. 3) was established by determination of absolute conformation and relative configuration at C(3) (pseudoaxial/pseudoequatorial) by combining CD and (1)H NMR spectroscopy.

Item Type:

Article

Uncontrolled Keywords:

1,4-benzodiazepin-2-ones; kinetic resolution; absolute configuration; asymmetric-synthesis

Subjects:

NATURAL SCIENCES > Chemistry

Divisions:

Division of Organic Chemistry and Biochemistry

Projects: