CHED 476 |
| Glucagon-like peptide-1 (GLP-1) is an endogenous peptide released in the insulin induction pathway when food is ingested. GLP-1 binds to the glucagon-like peptide-1 receptor (GLP-1R) in pancreatic b-cells, initiating a second messenger cascade resulting in the release of insulin into the bloodstream. As part of an SAR study of the N-terminal histidine (1) of GLP-1, which is essential to the activation of GLP-1R, we have prepared (2-imidazolyl)alanine (2) as a histidine analog. Hydroxymethylation of a protected imidazole occurs preferentially at the 2 position. Reaction of the protected hydroxymethylimidazole with thionyl chloride, followed by reaction with a chirally protected glycine anion gave protected 2 as a single diastereomer. Removal of the protecting groups gave 2 enantiomerically pure and in excellent yield. BOC protection of 2 followed by incorporation, by solid phase synthesis, into GLP-1 in place of histidine gave a GLP-1 analog which was screened for activation of GLP-1R.
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Undergraduate Research Poster Session: Organic Chemistry
11:00 AM-1:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster
Division of Chemical Education |
