Abstract
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).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Factor XIa / antagonists & inhibitors*
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Guanidines / chemical synthesis*
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Guanidines / chemistry
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Guanidines / pharmacology
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Humans
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Lactones / chemistry
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Molecular Structure
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Phenylacetates / chemical synthesis*
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Phenylacetates / chemistry
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Phenylacetates / pharmacology
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Porifera / chemistry
Substances
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Guanidines
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Lactones
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Phenylacetates
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clavatadine A
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Factor XIa