Pregnane-10,2-carbolactones from a Hawaiian Marine Sponge in the Genus Myrmekioderma

Abstract

Four new pregnanes, 3β,4β-dihydroxy-17-methyl-17α-pregna-5,13-diene-10,2-carbolactone (1), 6β-chloro-3β-hydroxy-17-methyl-17α-pregna-4,13-diene-10,2-carbolactone (2), 3β-hydroxy-6β-methoxy-17-methyl-17α-pregna-4,13-diene-10,2-carbolactone (3), and 3β,6β-dihydroxy-17-methyl-17α-pregna-4,13-diene-10,2-carbolactone (4), were isolated from an undescribed species of Myrmekioderma Ehlers along with the known pregnane carbolactone (5). The structures of the new compounds were determined by spectroscopic methods and comparison with previously described compounds. Compound 5 showed almost 4-fold activation of pregnane X receptor, while 2 inhibited BACE1 with an IC50 value of 82 μM.

Figure 1

Selected COSY (bold solid bars) and HMBC (H→C) correlations of 1.

Figure 2

Key ROESY correlations used to establish the relative configuration of 1. Lactone removed for clarity. Remaining centers established by ³J_H,H analysis

Scheme 1

Proposed biosynthesis of 1 from 5 via 1,2-methyl shifts.