Total synthesis of an anticancer natural product OSW-1 and studies toward the total synthesis of an anticancer natural product superstolide A

OSW-1 is a highly potent anticancer natural product. Its cytostatic activities are from 10 to 100 times more potent than many anticancer drugs in clinic use. Based on our newly developed α-halo vinyl ether methodology, a highly efficient and practical approach for the total synthesis of OSW-1 has been achieved with 28% overall yield.; Superstolide A is a highly potent anticancer marine natural product. Extensive studies toward the total synthesis of superstolide A have been carried out. The C20 ∼ C26 part of the molecule has been synthesized in 13 steps. Synthesis of the core structure of superstolide A is in progress and many model studies on the key step of Double Michael or Diels-Alder reactions have been investigated.; In order to achieve the total synthesis of OSW-1 and superstolide A, several new methodologies have been developed. They include: (1) α-halo vinyl ether chemistry; (2) α-halo vinyl sulfide chemistry; (3) a new methodology for the synthesis of (Z)-α,β-unsaturated ketones; (4) a new methodology for the generation of enolates from silyl enol ethers using potassium ethoxide; (5) a new methodology for chemoselective deprotection of the p-methoxybenzyl group; (6) α-halo vinyl ether as a novel substrate for Heck reaction. These methodologies not only played critical roles in the synthesis of OSW-1 and superstolide A, but also could find broad application in organic synthesis and the total synthesis of natural products.