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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-5-27
pubmed:abstractText
A solid-phase method for the synthesis of diacylglycerol lactones as protein kinase C ligands was developed, and a small array of nine compounds were selected with the idea of testing this methodology and forecasting the reliability of the biological data as a preamble for the construction of large chemical libraries to be synthesized under the same conditions. The process started with the loading of 5-(hydroxymethyl)-5-[(4-methoxyphenoxy)methyl]-3,4,5-trihydrofuran-2-one (1) to a 3,4-dihydro-2H-pyran resin packed inside IRORI MacroKan reactors. The elements of diversity were introduced at the alpha-alkylidene (R(1)) and acyl (R(2)) positions using a set of three different aldehydes and three different acid chlorides, respectively. An LDA-mediated aldol condensation with R(1)CHO in the presence of ZnCl(2) followed by a DBU-catalyzed elimination of the triflate of the resulting aldol gave the alpha-alkylidene intermediates as mixtures of geometric isomers. Removal of the aryl-protecting group followed by acylation with R(2)COCl introduced the second element of diversity. Acid-assisted cleavage of the compounds from the resin afforded the final targets. The biological results obtained using the crude samples directly obtained from the resin compared well with those from pure materials, as the K(i) values between the two sets varied only by a factor between 1.5 and 3.7.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3248-54
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Conformationally constrained analogues of diacylglycerol. 21. A solid-phase method of synthesis of diacylglycerol lactones as a prelude to a combinatorial approach for the synthesis of protein kinase C isozyme-specific ligands.
pubmed:affiliation
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.