Linked Life Data

18979467

Source:http://linkedlifedata.com/resource/pubmed/id/18979467

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2008-12-8
pubmed:abstractText
Combining the core structure of neopeltolide, lactone 16 a, with the oxazole-containing side chain 23 via a Mitsunobu reaction provided the cytotoxic natural product neopeltolide (2). The side chain 23 was prepared from oxazolone 24 via the corresponding triflate. Key steps in the preparation of 23 were a Sonogashira coupling, an enamine alkylation, and a Still-Gennari Horner-Emmons reaction. By changing the Leighton reagent in the allylation step, the 11-epimer of lactone 16 a, compound 50 was prepared. This led to 11-epi-neopeltolide 51. The 5-epimer of neopeltolide, compound 52, could be obtained from the minor isomer of the Prins cyclization. Furthermore, a range of analogues with modifications in the side chain were prepared. All derivatives were checked for toxicity effects on mammalian cell cultures and inhibitory effects on NADH oxidation in submitochondrial particles of bovine heart. Modifications in the lactone part are tolerated to some degree. On the other hand, shortening the distance between the oxazole and the lactone causes a significant drop in activity. Analogue 65 with an additional double bond is equally or even more active than neopeltolide itself.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1521-3765
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11132-40
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Total synthesis and biological activity of neopeltolide and analogues.
pubmed:affiliation
Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't