Linked Life Data

16776529

Source:http://linkedlifedata.com/resource/pubmed/id/16776529

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2006-6-16
pubmed:abstractText
In peptides and proteins, the peptide bond between an amino acid and proline exists as an equilibrium mixture of the cis-imide and trans-imide due to the low energy barrier in their interconversion. This feature greatly influences the structure and function of the proline-containing peptides and proteins. Therefore, restricting the amide bond with an (E)- or (Z)-alkene should provide a promising method for elucidating the structure-activity relationships of the peptide and the proteins. In this report, the regio- and stereoselective synthesis of cis-alanylproline (Ala-Pro) type (Z)-alkene dipeptide mimetic is described. The key steps of this synthesis are to introduce a C3 unit onto a gamma-phosphoryloxy-alpha,beta-unsaturated-delta-lactam with an organocopper-mediated anti-S(N)2' reaction and subsequently construct a five-membered proline-like cyclic structure with an intramolecular Suzuki coupling reaction. Hydrolysis of the amide bond in the resulting bicyclic lactam yields the desired cis-Ala-Pro type (Z)-alkene dipeptide isostere. The presented synthetic methodology should be applicable to the general syntheses of other cis-aminoacylproline type (Z)-alkene dipeptide mimetics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3263
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4969-79
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Stereoselective synthesis of (Z)-alkene-containing proline dipeptide mimetics.
pubmed:affiliation
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't