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Synthesis of the First Fully Functionalized Core of the Zaragozic Acids/Squalestatins
Author(s) -
Nicolaou Kyriacos C.,
Nadin Alan,
Leresche James E.,
Greca Susan La,
Tsuri Tatsuo,
Yue Eddy W.,
Yang Zhen
Publication year - 1994
Publication title -
angewandte chemie international edition in english
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 0570-0833
DOI - 10.1002/anie.199421871
Subject(s) - total synthesis , trimethylsilyl , chemistry , diene , sequence (biology) , combinatorial chemistry , stereochemistry , side chain , organic chemistry , biochemistry , natural rubber , polymer
Step by step the first total synthesis was approached: of the zaragozic acids/ squalestatins showing potential therapeutic value for lowering the serum cholesterol concentration, zaragozic acid A/squalestatin SI ( 1 ), the most abundant member of a new class of naturally occurring products, has now been synthesized via the key intermediates 2 and 3 . Initially the projected final sequence ( 2 → 1 ) was achieved, and the side chains attached to C1 and C6 were prepared through efficient asymmetric syntheses. The first synthesis of the highly oxygenated “core”, which is characteristic of this class of natural products, was achieved from a simple prochiral diene via intermediate 3 . Finally the synthetic route 3 → 2 was developed to successfully complete the total synthesis. Bn benzyl, PMB para ‐methoxybenzyl, TMS trimethylsilyl.