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Article

Divergent Asymmetric Total Synthesis of All Four Pestalotin Diastereomers from (R)-Glycidol

Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan
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Academic Editor: Rafael Chinchilla
Molecules 2020, 25(2), 394; https://doi.org/10.3390/molecules25020394
Received: 28 December 2019 / Revised: 12 January 2020 / Accepted: 13 January 2020 / Published: 17 January 2020
(This article belongs to the Special Issue Development of Asymmetric Synthesis)
All four chiral pestalotin diastereomers were synthesized in a straightforward and divergent manner from common (R)-glycidol. Catalytic asymmetric Mukaiyama aldol reactions of readily-available bis(TMSO)diene (Chan’s diene) with (S)-2-benzyloxyhexanal derived from (R)-glycidol produced a syn-aldol adduct with high diastereoselectivity and enantioselectivity using a Ti(iOPr)4/(S)-BINOL/LiCl catalyst. Diastereoselective Mukaiyama aldol reactions mediated by catalytic achiral Lewis acids directly produced not only a (1′S,6S)-pyrone precursor via the syn-aldol adduct using TiCl4, but also (1′S,6R)-pyrone precursor via the antialdol adduct using ZrCl4, in a stereocomplementary manner. A Hetero-Diels-Alder reaction of similarly available mono(TMSO)diene (Brassard’s diene) with (S)-2-benzyloxyhexanal produced the (1′S,6S)-pyrone precursor promoted by Eu(fod)3 and the (1′S,6R)-pyrone precursor Et2AlCl. Debenzylation of the (1′S,6S)-precursor and the (1′S,6R)-precursor furnished natural (−)-pestalotin (99% ee, 7 steps) and unnatural (+)-epipestalotin (99% ee, 7 steps), respectively. Mitsunobu inversions of the obtained (−)-pestalotin and (+)-epipestalotin successfully produced the unnatural (+)-pestalotin (99% ee, 9 steps) and (−)-epipestalotin (99% ee, 9 steps), respectively, in a divergent manner. All four of the obtained chiral pestalotin diastereomers possessed high chemical and optical purities (optical rotations, 1H-NMR, 13C-NMR, and HPLC measurements). View Full-Text
Keywords: asymmetric total synthesis; divergent synthesis; pyran-2-one; pestalotin; epipestalotin; asymmetric Mukaiyama aldol reaction; hetero Diels-Alder reaction; Mitsunobu inversion; Chan’s diene; Brassard’s diene asymmetric total synthesis; divergent synthesis; pyran-2-one; pestalotin; epipestalotin; asymmetric Mukaiyama aldol reaction; hetero Diels-Alder reaction; Mitsunobu inversion; Chan’s diene; Brassard’s diene
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MDPI and ACS Style

Moriyama, M.; Nakata, K.; Fujiwara, T.; Tanabe, Y. Divergent Asymmetric Total Synthesis of All Four Pestalotin Diastereomers from (R)-Glycidol. Molecules 2020, 25, 394. https://doi.org/10.3390/molecules25020394

AMA Style

Moriyama M, Nakata K, Fujiwara T, Tanabe Y. Divergent Asymmetric Total Synthesis of All Four Pestalotin Diastereomers from (R)-Glycidol. Molecules. 2020; 25(2):394. https://doi.org/10.3390/molecules25020394

Chicago/Turabian Style

Moriyama, Mizuki, Kohei Nakata, Tetsuya Fujiwara, and Yoo Tanabe. 2020. "Divergent Asymmetric Total Synthesis of All Four Pestalotin Diastereomers from (R)-Glycidol" Molecules 25, no. 2: 394. https://doi.org/10.3390/molecules25020394

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