Total Syntheses of Zaragozic Acids A and C by a Carbonyl Ylide Cycloaddition Strategy
- 27 November 2006
- journal article
- research article
- Published by Wiley in Chemistry – A European Journal
- Vol. 12 (35) , 8898-8925
- https://doi.org/10.1002/chem.200601212
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 LiBH4 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 [Rh2(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).Keywords
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