Monamphilectine A, a potent antimalarial β-lactam from marine sponge Hymeniacidon sp: isolation, structure, semisynthesis, and bioactivity

Abstract

Monamphilectine A (1), a new diterpenoid β-lactam alkaloid showing potent antimalarial activity, was isolated in milligram quantities following bioassay-directed extraction of a Puerto Rican marine sponge Hymeniacidon sp. Its structure, established by interpretation of spectral data, was confirmed unequivocally by chemical interconversion and comparison of physical, chemical, and bioactivity data with the natural product. The one-step semisynthesis of monamphilectine A was based on a multicomponent Ugi reaction that also established its absolute stereostructure.

Figure 1

Monamphilectine A (left) and partial structures for 1 generated from ¹H–¹H COSY, HSQC, and HMBC correlations.

Scheme 1

Semisynthesis of Monamphilectine A (1) from 2