TY - JOUR
T1 - Total Synthesis of Alcyonolide
AU - Fumiyama, Hitoshi
AU - Takahashi, Arata
AU - Suzuki, Yuma
AU - Fujioka, Naoto
AU - Matsumoto, Hirotake
AU - Hosokawa, Seijiro
N1 - Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/11/18
Y1 - 2022/11/18
N2 - The total synthesis of alcyonolide, an antitumor xenicn diterpenoid, has been achieved. The inverse electron demand hetero-Diels-Alder reaction using a dienophile possessing an electron-withdrawing group provided the endo adduct which included a condensed lactone and dihydropyran rings with the desired three stereogenic centers. After introduction of the side chain by the Negishi coupling, the lactone ring was opened to form a Weinreb amide. The sequential transformation including conversion of Weinreb amide to aldehyde, PMB to acetate, and allylation of the aldehyde gave a mixture of separable four diastereomers. The desired stereoisomer was submitted to the 2,2,6,6-tetramethylpiperidine 1-oxyl oxidation, which afforded the δ-lactone and the methyl ketone side chain. Finally, the olefin metathesis of the desired isomer gave racemic alcyonolide.
AB - The total synthesis of alcyonolide, an antitumor xenicn diterpenoid, has been achieved. The inverse electron demand hetero-Diels-Alder reaction using a dienophile possessing an electron-withdrawing group provided the endo adduct which included a condensed lactone and dihydropyran rings with the desired three stereogenic centers. After introduction of the side chain by the Negishi coupling, the lactone ring was opened to form a Weinreb amide. The sequential transformation including conversion of Weinreb amide to aldehyde, PMB to acetate, and allylation of the aldehyde gave a mixture of separable four diastereomers. The desired stereoisomer was submitted to the 2,2,6,6-tetramethylpiperidine 1-oxyl oxidation, which afforded the δ-lactone and the methyl ketone side chain. Finally, the olefin metathesis of the desired isomer gave racemic alcyonolide.
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U2 - 10.1021/acs.joc.2c02031
DO - 10.1021/acs.joc.2c02031
M3 - Article
AN - SCOPUS:85141589865
SN - 0022-3263
VL - 87
SP - 15492
EP - 15498
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 22
ER -