SYNTHESIS OF SESAMOLIN DERIVATIVES VIA NUCLEOPHILIC SUBSTITUTION REACTION AND THEIR BIOLOGICAL ACTIVITIES

Abstract

The synthesis of 10 new alkyloxy samins (2a-2j) was achieved by a simple one-step approach from sesamolin. The synthetic pathway involved acid-catalyzed nucleophilic substitution at acetal moiety with a variety of alcohol, affording fair to good yield (55-82%) of the desired products. The relative configuration established by analysis of coupling constant and NOESY correlations indicated that this nucleophilic substitution underwent with retention of configuration. All newly synthesized 2a-2j compounds were evaluated for DPPH radical scavenging and α-glucosidase inhibitory activity. Alcohol-derived analogues 2a-2g showed slightly weaker activity (~1.2-1.5 times) with SC50 values in range 27.32-34.00 mM whereas diol-derived analogues 2h-2j revealed significantly weaker scarvening activity (~1.6-2.3 times) compared with the parent starter sesamolin (SC50 22.59 mM). Having identical chain length, the analogue possessing one additional hydroxyl group was likely to reduce scavenging activity in some extend. As for α-glucosidase inhibitory activity, all alkyloxy samins showed no inhibitory activity against both yeast and rat intestinal glucosidases. Because bioactivities of sesamolin and its analogues were comparable, it is of interest to evaluate their stability toward acid condition. On examination in CD3OD catalyzed by CF3CO2D, sesamolin underwent degradation completely within 3 hours whereas alkyloxy samin remained unchanged.