1. Total synthesis of marine natural products possessing spiroketal: Alotaketal and phorbaketal. 2. Confirmation of absolute stereochemistry of carvotacetones via circular dichroism and total synthesis.

Abstract

1. Alotaketals and Phorbaketals were isolated from marine sponge, Hamigera sp. and Phorbas sp. in 2009. They were novel sesterterpenoid natural products including unsaturated spiroketal feature. These natural products have received attention because of their structural features along with variety of biological activities suchs as activation of cAMP cell signaling pathway. A gold catalyzed tandem spiroketalization of epoxyalkynes accompanied by rearrangement of an expoxide to an allylic alcohol was developed for the construction of an unsaturated [6,6]-spiroketal. this new synthetic route to unsaturated [6,6]spiroketal enabled a facile total synthesis of alotaketal A and phorbaketal A in 11 and 14 steps.

2. Structural determination of natural products even with sub-miligram quatities, has become quotidian process of natural product chemists with development of spectroscopic methods such as NMR, IR, MS and X-ray crystallography. Even so, determining the absolute stereochemistry of natural products still remains tricky unless X-ray crystallography can be used. it can be seen in the case of carvotacetone natural products. Since 1979, 33 different carvotacetones were reported and their absolute stereochemistry has not been clearly demonstrated so far. First we deduced the absolute configuration of most of the carvotacetones by comparing the CD spectra of natural products and synthetic compound possessing similar sturcture and identical relative stereochemistry with that of natural carvotacetones. Some of carvotacetones indicated opposite opical rotation to that of the other. Thus we verified they have opposite absolute stereochemistry via total synthesis of the carvotacetone. As the result, it was revealed that both enantiomer of carvotacetones can exist in nature.