ORGN 165 |
| Nicotinamide adenine dinucleotide (NAD+, 1) is the substrate for both poly(ADP-ribose) polymerase-1 (PARP-1) and inosine-5'-monophosphate dehydrogenase (IMPDH), important enzymes implicated in cancer development. We herein describe an innovative approach to the synthesis of a cyclic sulfoximine 2-deoxyriboside mimic, where the anomeric carbon has been replaced by the sulfoximine group. Sulfoximines possess extremely versatile chemistry and their use in the design of ribose mimics has not been reported previously. A key step in our ongoing studies towards the target 2 involves a thio-Mitsunobu reaction of a sulfur nucleophile 3 and a homochiral dioxolane compound 4. The two diastereoisomers of an important, novel intermediate 5 have been separated and the stereochemistry at the sulfur centre established by X-ray crystallography. Development of synthetic routes from this intermediate to the target cyclic sulfoximine will be reported.
|
|
Asymmetric Reactions and Syntheses, Metal-Mediated Reactions, Combinatorial, Parallel, and Solid-Phase Chemistry
8:00 PM-10:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster
Division of Organic Chemistry |
