Total synthesis of potential anti-tumor agent, (-)-dictyostatin
Abstract
Since the discovery from the Pacific Yew Tree in 1971, paclitaxel (Taxol ®) has been a matter of keen interest and holds a major share in the anticancer drug market today. It binds and stabilizes the microtubules leading to the arrest of mitosis at the G2M phase. However, it suffers from certain limitations such as low solubility in water and toxicity. This has led to the search for drugs with similar action. Dictyostatin is a marine sponge derived natural product whose structure was tentatively assigned in 1994. It displays a powerful growth inhibitory activity against a number of human cancer cell lines. Its cytotoxicity is more pronounced than that of Taxol® and is further retained against (P-glycoprotein efflux-mediated) Taxol-resistant cell lines. Thus, dictyostatin represents a promising antimitotic natural product drug lead for cancer chemotherapy development. A total synthesis of dictyostatin has been achieved using Brown's crotylboration to achieve eight of the eleven chiral centers present in the molecule. The yield for the 26-step longest linear sequence starting from Roche ester is ∼4%.
Degree
Ph.D.
Advisors
Ramachandran, Purdue University.
Subject Area
Organic chemistry
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