Clavatadine A

The first total synthesis of clavatadine B (2), a natural product found to be a selective human blood coagulation factor XIa inhibitor, is described. A convergent approach that exemplifies the advantages of direct, early stage guanidinylation provided an immediate clavatadine B precursor, which was assembled in an efficient manner using known synthetic precursors of the structurally related natural product clavatadine A (1). Global deprotection cleanly provided clavatadine B in only four steps from a known derivative of homogentisic acid lactone (longest linear sequence, 75% overall yield).