A Second-Generation Synthesis of the C1−C28 Portion of the Altohyrtins (Spongistatins)

A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1−C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the...

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Veröffentlicht in:	Journal of the American Chemical Society 2003-10, Vol.125 (42), p.12836-12843
Hauptverfasser:	Hubbs, Jed L, Heathcock, Clayton H
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic Agents - chemical synthesis Catalysis Macrolides - chemical synthesis Palladium - chemistry Spiro Compounds - chemistry Vinyl Compounds - chemistry
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container_title	Journal of the American Chemical Society
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creator	Hubbs, Jed L Heathcock, Clayton H
description	A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1−C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the troublesome C13−C15 segment. Our general approach to the C16−C28 (CD) spiroketal has been retained, but some improvements have been made. Most notably, the kinetically controlled CD-spiroketalization reaction now proceeds in high yield with excellent diastereoselection. This new strategy uses the anti-aldol coupling used in our first-generation synthesis to join AB and CD fragments. A total of 9.6 g of intermediate 57 has been produced using this improved route.
doi_str_mv	10.1021/ja030316h
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Am. Chem. Soc</addtitle><description>A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1−C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the troublesome C13−C15 segment. Our general approach to the C16−C28 (CD) spiroketal has been retained, but some improvements have been made. Most notably, the kinetically controlled CD-spiroketalization reaction now proceeds in high yield with excellent diastereoselection. This new strategy uses the anti-aldol coupling used in our first-generation synthesis to join AB and CD fragments. 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subjects	Antineoplastic Agents - chemical synthesis Catalysis Macrolides - chemical synthesis Palladium - chemistry Spiro Compounds - chemistry Vinyl Compounds - chemistry
title	A Second-Generation Synthesis of the C1−C28 Portion of the Altohyrtins (Spongistatins)
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