Structural flexibility in the biocatalyst-mediated functionalization of ring ‘A’ in salannin, a tetranortriterpene from Azadirachta indica

Abstract

Nocardia sp. quantitatively converts salannin 1 and 3-de-O-acetylsalannin 2 (C-seco limonoids) into 3-deacetoxy-1-de[(E)-2-methylbut-2-enoyloxy]salannin-1-en-3-one 10, a novel and potentially bioactive compound with an α,β-unsaturated ketone moiety in ring ‘A’. In order to establish the sequence of events involved in this transformation and the structural specificity of this bacterial system, several new derivatives of salannin 1 have been prepared. These studies have indicated that the transformation is initiated by deacetylation at C-3, followed by oxidation of the secondary hydroxy group to 3-keto, which appears to facilitate the elimination of the tigloyloxy/acetoxy group at C-1 with the formation of an olefinic linkage between C-1 and C-2.

The organism very efficiently transforms some of the derivatives of salannin into their corresponding compounds possessing an enone system in ring ‘A’, an essential pre-requisite for various biological activities. Some of the C-seco limonoids prepared in the present study, viz. 10, 1,2-didehydro-1,3-dideoxy-3-oxosalannic acid 18, 3-deacetoxy-1-de[(E)-2-methylbut-2-enoyloxy]-20,21,22,23-tetrahydrosalannin-1-en-3-one 15 and 1,2-didehydro-1,3-dideoxy-3-oxosalannol 23 were hitherto not known.

p