Synthesis of Bryostatin 1 Keck

A unique approach to the requisite C-ring fragment 51 is achieved through reductive cyclization of olefinic ester 55 by way of the titanium alkylidene, as described by Rainer and Nicolaou [59]. The olefinic ester 55 is prepared in ten steps from (R)-isobutyl lactate using consecutive chelation-controlled 

Conversion of the A-ring aldehyde 50 to hydroxyallylsilane 57 is accomplished in a three-step sequence involving addition of allylstannane 49 followed by oxidation-reduction for diastereomeric enrichment at Cll. With both hydroxyallylsilane 57 and aldehyde 51 in hand, intermolecular Prins pyran annulation proceeds smoothly to furnish the tricyclic compound 58 in 61 % isolated yield. 

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