Synthetic Studies on Aphidicolane and Stemodane Diterpenes. V. A Facile Formal Total Synthesis of (.+-.)-Aphidicolin via a Lewis Acid-Mediated Stereoselective Spiroannelation.
Year: 1995
Type: article
Abstract: 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).
DOI: 10.1248/cpb.43.1407
Institution: The University of Osaka
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W2011457519