Enantioselective Syntheses of the Methylene- and Fluoromethylene-Phosphonate Analogues of 3-Phospho-D-Glyceric Acid |
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Authors: | Marianne Broekman Abdul Rashid G Michael Blackburn |
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Institution: | Department of Chemistry , Sheffield University , Sheffield , S3 7HF , UK |
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Abstract: | Abstract The racemic methylene analogue of 3-phospho-D-glyceric acid1–4 has been shown to be a viable substrate for the combined action of 3-phosphoglycerate kinase, PGK, and glyceraldehyde 3-phosphate dehydrogenase, GPD. We have shown that replacement of CH2 by CHF or CF2 in a variety of nucleotide analogues4,5 can lead to improved Performance as enzyme substrates or inhibitors. We have therefore undertaken enantiospecific syntheses of the methylene- and fluoro-methylene-analogues of 3-phospho-D-glyceric acid to investigate their interaction with PGK and GPD and explore whether the fluorine atom in the latter can mimic an oxygen lone-pair in binding to enzymes. |
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