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Formal Total Synthesis of Fostriecin by 1,4‐Asymmetric Induction with an Alkyne–Cobalt Complex
Author(s) -
Hayashi Yujiro,
Yamaguchi Hirofumi,
Toyoshima Maya,
Okado Kotaro,
Toyo Takumi,
Shoji Mitsuru
Publication year - 2010
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.201000795
Subject(s) - stereocenter , asymmetric induction , alkyne , stereochemistry , chemistry , aldehyde , moiety , enantioselective synthesis , formal synthesis , total synthesis , combinatorial chemistry , organic chemistry , catalysis
The synthesis of a protected dephosphofostriecin, and thereby a formal synthesis of fostriecin, has been accomplished. The synthetic challenges were the construction of four stereogenic centers and the conformationally labile cis ‐ cis ‐ trans ‐triene moiety. Previous total syntheses have employed at least two asymmetric reactions that required the use of an external chiral auxiliary. Although remote stereoinduction in a 1,4‐relationship is considered difficult, we have developed a notable 1,4‐asymmetric induction that utilizes an alkyne–cobalt complex for the control of C5 stereochemistry by the C8 stereogenic center. The stereochemistry at C11 was established by 1,3‐asymmetric induction with a higher‐order alkynyl‐zinc reagent. Thus, only one asymmetric reaction requiring an external chiral auxiliary was employed in this route. The labile cis ‐ cis ‐ trans ‐triene unit was constructed at a late stage of the synthesis by diastereoselective coupling of a dienyne and an aldehyde unit, followed by reduction.