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

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 alpha,beta-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 systemin 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-tetrahydrosal annin-1-en-3-one 15 and 1,2-didehydro-1,3-dideoxy-3-oxosalannol 23 were hitherto not known.