Premium
Total Syntheses of Zaragozic Acids A and C by a Carbonyl Ylide Cycloaddition Strategy
Author(s) -
Hirata Yuuki,
Nakamura Seiichi,
Watanabe Nobuhide,
Kataoka Osamu,
Kurosaki Takahiro,
Anada Masahiro,
Kitagaki Shinji,
Shiro Motoo,
Hashimoto Shunichi
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200601212
Subject(s) - ylide , chemistry , cycloaddition , regioselectivity , dihydroxylation , ethyl diazoacetate , alkene , enantioselective synthesis , ketone , organic chemistry , catalysis , stereochemistry , medicinal chemistry , cyclopropanation
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 ).