Total Synthesis of (+)-Irciniastatin A (a.k.a. Psymberin) and (鈭?-Irciniastatin B

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• 作者：Chihui An ; Jon A. Jurica ; Shawn P. Walsh ; Adam T. Hoye ; Amos B. Smith ; III
• 刊名：The Journal of Organic Chemistry
• 出版年：2013
• 出版时间：May 3, 2013
• 年：2013
• 卷：78
• 期：9
• 页码：4278-4296
• 全文大小：741K
• 年卷期：v.78,no.9(May 3, 2013)
• ISSN：1520-6904

文摘

A unified synthetic strategy to access (+)-irciniastatin A (a.k.a. psymberin) and (鈭?-irciniastatin B, two cytotoxic secondary metabolites, has been achieved. Highlights of the convergent strategy comprise a boron-mediated aldol union to set the C(15)鈥揅(17) syn鈥搒yn triad, reagent control to set the four stereocenters of the tetrahydropyran core, and a late-stage Curtius rearrangement to install the acid-sensitive stereogenic N,O-aminal. Having achieved the total synthesis of (+)-irciniastatin A, we devised an improved synthetic route to the tetrahydropyran core (13 steps) compared to the first-generation synthesis (22 steps). Construction of the structurally similar (鈭?-irciniastatin B was then achieved via modification of a late-stage (鈭?-irciniastatin A intermediate to implement a chemoselective deprotection/oxidation sequence to access the requisite oxidation state at C(11) of the tetrahydropyran core. Of particular significance, the unified strategy will permit late-stage diversification for analogue development, designed to explore the biological role of substitution at the C(11) position of these highly potent tumor cell growth inhibitory molecules.