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Total Synthesis of the 7,10‐Epimer of the Proposed Structure of Amphidinolide N, Part I: Synthesis of the C1–C13 Subunit
Author(s) -
Ochiai Koji,
Kuppusamy Sankar,
Yasui Yusuke,
Okano Tsubasa,
Matsumoto Yasunobu,
Gupta Nishant R.,
Takahashi Yohei,
Kubota Takaaki,
Kobayashi Jun'ichi,
Hayashi Yujiro
Publication year - 2016
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.201504674
Subject(s) - chemistry , tetrahydropyran , total synthesis , aldol reaction , epimer , stereochemistry , enantioselective synthesis , intramolecular force , sharpless epoxidation , epoxide , protein subunit , ring (chemistry) , catalysis , organic chemistry , biochemistry , gene
Amphidinolide N, the structure of which has been recently revised, is a 26‐membered macrolide featuring allyl epoxide and tetrahydropyran moieties with 13 chiral centers. Due to its challenging structure and extraordinary potent cytotoxicity, amphidinolide N is a highly attractive target of total synthesis. During our total synthesis studies of the 7,10‐epimer of the proposed structure of amphidinolide N, we have synthesized the C1–C13 subunit enantio‐ and diastereoselectively. Key reactions include an l ‐proline catalyzed enantioselective intramolecular aldol reaction, Evans aldol reaction, Sharpless asymmetric epoxidation and Tamao–Fleming oxidation. To aid late‐stage manipulations, we also developed the 4‐( N ‐benzyloxycarbonyl‐ N ‐methylamino)butyryl group as a novel ester protective group for the C9 alcohol.