Synthesis Of Cabraleahydroxylactone And Its Activity Toward Alpha-Glucosidase

Abstract

Cabraleahydroxylactone (1a) is a naturally occurring compound that exhibits potential biological activities. While the natural resources yielded negligible quantities which are insufficient for further investigation, it is crucial to develop synthetic methods to overcome the limitation. This project was able to utilize cabralealactone (2) as a starting material for obtaining 1a. By employing aluminum trichloride hexahydrate and sodium cyanoborohydride, a reduction of cabralealactone (2) successfully produced both diastereomers 1a and 1b. The yield of 1a surprisingly increased in a mixture with 1b, which was the only diastereomer observed in previous reports. Interestingly, the inhibitory activity against α-glucosidase illustrated an improvement with the diastereomers compared to cabralealactone and its precursor dipterocarpol (3). Compound 1a displayed the strongest inhibition with IC50 at 43.79 ± 1.81 µg/mL, followed by 1b (66.82 ± 0.758 µg/mL) and 2 (63.55 ± 0.96 µg/mL), while 3 exhibited the weakest inhibition (105.85 ± 2.75 µg/mL). Enzymatic kinetic study revealed that 1a and 1b functioned as partially non-competitive and partially competitive inhibitors, respectively. Notably, a synergistic effect of 1a and 1b was observed, suggesting a potential advantage of using the diastereomeric mixture over the separated forms. Furthermore, the mixture of these diastereomers from a practical reduction reaction also illustrated a combined effect on α-glucosidase inhibition.