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Total Syntheses of Zaragozic Acids A and C by a Carbonyl Ylide Cycloaddition Strategy

✍ Scribed by Yuuki Hirata; Seiichi Nakamura; Nobuhide Watanabe; Osamu Kataoka; Takahiro Kurosaki; Masahiro Anada; Shinji Kitagaki; Motoo Shiro; Shunichi Hashimoto

Book ID
102794547
Publisher
John Wiley and Sons
Year
2006
Tongue
English
Weight
923 KB
Volume
12
Category
Article
ISSN
0947-6539

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✦ Synopsis

Abstract

A carbonyl ylide cycloaddition approach to the squalene synthase inhibitors zaragozic acids A and C is described. The carbonyl ylide precursor 8 was synthesized starting from di‐tert‐butyl D‐tartrate (47) via an eleven‐step sequence involving the regioselective reduction of the mono‐MPM (MPM = 4‐methoxybenzyl) ether 48 with LiBH~4~ and the diastereoselective addition of sodium tert‐butyl diazoacetate to α‐keto ester 10. The reaction of α‐diazo ester 8 with 3‐butyn‐2‐one (40) in the presence of a catalytic amount of [Rh~2~(OAc)~4~] gave the desired cycloadduct 59 as a single diastereomer. The dihydroxylation of enone 59 followed by sequential transformations permitted the construction of the fully functionalized 2,8‐dioxabicyclo[3.2.1]octane core 5. Alkene 79 derived from 5 serves as a common precursor to zaragozic acids A (1) and C (2), since the elongation of the C1 alkyl side chain can be attained by olefin cross‐metathesis, especially under the influence of Blechert's catalyst (85).

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Total Synthesis of the Squalene Synthase
Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C by a Carbonyl Ylide Cycloaddition Strategy
✍ Seiichi Nakamura; Yuuki Hirata; Takahiro Kurosaki; Masahiro Anada; Osamu Kataoka 📂 Article 📅 2003 🏛 John Wiley and Sons 🌐 English ⚖ 149 KB 👁 2 views

The zaragozic acids and squalestatins, a novel family of fungal metabolites isolated and characterized by researchers at Merck [1] and Glaxo, [2] respectively, in 1992, are the most potent inhibitors of squalene synthase known to date. [3] Some members of this family have also demonstrated the abili

Syntheses of the C-1 alkyl side chains o
Syntheses of the C-1 alkyl side chains of Zaragozic acids A and C
✍ Jordi Bach; Marta Galobardes; Jordi Garcia; Pedro Romea; Cristina Tey; Fèlix Urp 📂 Article 📅 1998 🏛 Elsevier Science 🌐 French ⚖ 200 KB

Asymmetric syntheses of the C-1 alkyl side chains of Zaragozic acids A and C from a common chiral precursor 4 are reported. The stereoselective reduction of unsaturated ketones 8 and 10 is the key step of both syntheses.