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Aruncin B: Synthetic Studies, Structural Reassignment and Biological Evaluation
Author(s) -
Ribaucourt Aubert,
Towers Christopher,
JosaCulleré Laia,
Willenbrock Frances,
Thompson Amber L.,
Hodgson David M.
Publication year - 2017
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.201702949
Subject(s) - sonogashira coupling , chemistry , stereochemistry , alkene , metathesis , ring closing metathesis , moiety , combinatorial chemistry , structural isomer , sequence (biology) , sodium salt , organic chemistry , biochemistry , palladium , inorganic chemistry , polymer , polymerization , catalysis
A ring‐closing alkene metathesis (RCM)/ oxyselenation‐selenoxide elimination sequence was established to the sodium salts E ‐ and Z ‐ 25 of the originally proposed structure for the recently isolated cytotoxin aruncin B ( 1 ), as well as to the sodium salt Z ‐ 34 of a related ethyl ether regioisomer; however, none of their corresponding free acids could be obtained. Their acid sensitivity, together with detailed analysis of the spectroscopic data indicated that profound structural revision was necessary. This led to reassignment of aruncin B as a Z ‐γ‐alkylidenebutenolide Z ‐ 36 . Although a related RCM/ oxyselenation‐selenoxide elimination sequence was used to confirm the γ‐alkylidenebutenolide motif, a β‐iodo Morita‐Baylis–Hillman reaction/ Sonogashira cross‐coupling‐5‐ exo‐dig lactonisation sequence was subsequently developed, due to its brevity and flexibility for diversification. Aruncin B ( 36 ), together with 14 γ‐alkylidenebutenolide analogues, were generated for biological evaluation.