30 海洋産の抗腫瘍物質プライオスタチン7の全合成研究(口頭発表の部)  [in Japanese] 30 Studies Toward the Total Synthesis of Bryostatin 7  [in Japanese]

Bryostatin 7 (2), isolated in minute quantities from the marine organism Bugula neritina, exhibits promising antineoplastic activity. Its unique structual feature and physiological properties as well as the difficulty in its isolation from natural sources make this compound an attractive synthetic target. Our project directed toward this objective has now reached its final stage and the seco-acid corresponding to (2) is in our hands. Scheme 2 outlines a retrosynthesis of (2). Intermediate (10) was prepared through a route similar to that for fragment AB (7) (Scheme 1), while assembly of C (5) and D (6) led to CD (8) (Scheme 4). Scheme 6 outlines the coupling of A'B-CD and subsequent transformation of (21) to the seco-acid derivative (23). Thus the coupling employed the Julia-Lythgoe procedure with PhLi as a base for deprotonation of (8). The oxidation states both at the C-31 and C-35 positions was adjusted and the C-20 hydroxy group converted to the acetoxy to provide compound (22). At this stage the last asymmetric center was formed by using (12) with 3:1 stereoselection. The major (23) was isolated after selective deprotection of acetonide. The only task that remains to be achieved is macrolactonization.