Formal Synthesis Of The Natural Product Clavosolide A

Marine sponges have provided an inexhaustible supply of bioactive metabolites.There was a report by Fu that Faulkner and Rao isolated a suite of unusual metabolites,Clavosolides A and its familiy compounds from the crude extract of the sponge Myriastra clavosa from the Philippines in 2001.It is an unusual symmetrical 16-membered ring dilactone assembled on a functionalized tetrahydropyran core with a permethylated xylose moiety which was assumed to have the more usual D-configuration and has many chiral cores.In this paper,a novel,simple and efficient synthesis strategy is designed to complete the formal synthesis of the natural product Clavosolide A,which uses the Cram-Reetz rule to control the Mukaiyama Aldol reaction on selectively construction of the trans-1,3-dihydroxy structure and finish the synthesis of the tetrahydropyran ring with thermodynamics theory.Specific routes include the Evans Aldol reaction used to construct the first chiral center,Boron-induced reduction reaction to build the second chiral center,Mukaiyama Aldol reaction to build the third and fourth chiral centers and Oxygen-Michael addition reaction to construct the tetrahydropyran ring and the fifth chiral center.This paper designs a general synthetic strategy of Clavosolide A,which use the Mukaiyama Aldol reaction,Evans Aldol reaction and Michael addition reaction to finish the formal synthesis.It also could be applied on the synthesis of his family compounds and other similar natural products.At the same time,this strategy has important implications for the research of Clavosolide A’s possible bioactivity.