Synthesis of a Simplified Bryostatin C-Ring Analogue That Binds to the CRD2 of Human PKC-α and Construction of a Novel BC-Analogue by an Unusual Julia Olefination Process

The synthesis of two truncated bryostatin analogues 2 and 3 is described. High-field NMR measurements on the C-ring analogue 3 in C2H3CN containing 25% 2H2O have shown that it binds to the CRD2 of human PKC-α at virtually the same position as phorbol-13-acetate (PA) and bryostatin 1 (1). NMR titration studies have also revealed that 3 binds to the CRD2 with a potency similar in magnitude to PA but much less potently than 1