Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Synthetic Studies on Aphidicolane and Stemodane Diterpenes. V. A Facile Formal Total Synthesis of (±)-Aphidicolin via a Lewis Acid-Mediated Stereoselective Spiroannelation
田中 徹明奥田 修村上 和夫吉野 仁三神山 秀勲神田 篤金 相元岩田 宙造
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1995 年 43 巻 8 号 p. 1407-1411

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Formal total synthesis of (±)-aphidicolin (1) was achieved via a Lewis acid-mediated stereoselective spiroannelation reaction as a key step. The bisbenzyl acetal (2) was synthesized from the readily available dimethyl acetal (4). Treatment of 2 with trimethylsilyl trifluoromethanesulfonate (TMSOTf) afforded a 69 : 31 mixture of the spirocyclic enones (9 and 10) in excellent yield. The tricyclic ketal-ketone (3) corresponding to the B/C/D rings of 1 was easily generated from the enone (9) by intramolecular alkylation and catalytic hydrogenation as principal steps. The A-ring construction was performed by a procedure similar to one used previously. Barbier reaction of 14, followed by oxidative rearrangement, stereoselective 1, 4-addition of a methyl group, and subsequent intramolecular aldol-condensation afforded the tetracyclic enone (18), which has already been transformed into (±)-aphidicolin (1).
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