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Merck
CN

Total synthesis of clavatadine A.

Journal of natural products (2014-12-18)
Stephanie J Conn, Shannon M Vreeland, Alexandra N Wexler, Rebecca H Pouwer, Rebecca N Pouwer, Ronald J Quinn, Stephen Chamberland
摘要

The first total synthesis of the potent and selective human blood coagulation factor XIa inhibitor clavatadine A (1) is described. Direct, early-stage guanidinylation enabled rapid, convergent access to an immediate clavatadine A precursor. Concomitant lactone hydrolysis and guanidine deprotection with aqueous acid cleanly provided clavatadine A (1) in only four steps (longest linear sequence, 41-43% overall yield).

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Crown-cap crimper, H × diam. 21 1/2 in. × 12 in.