|M.Sc Student||Sandlers Yana|
|Subject||Design and Synthesis of Mechanism Based Inhibitor of the|
|Department||Department of Chemistry||Supervisor||Professor Timor Baasov|
Scheme 1a: Proposed mechanistic pathway for KDO8P-synthase-catalazed reacion
Although this proposal was based on reasonable chemical grounds, there is no direct evidence for the formation of 2 as a reaction intemediate.Therefore, we designed, structure 5 which is a stable phosphonate analogue of the putative hemiketal intermediate 2.
We have developed two alternative synthetic pathways for the preparation of 5. We have succesfully accomplished insertion of the phosphonate group and have separated and characterized diastreriomes (at C-2) of the phosphonate 13.
The alternative pathway includes synthesis of the ketoester 23.
Compound 23 was then transformed to the diastereomeric mixture of 24, which after several steps of synthesis afforded protected phosphonophosphate 28 as a mixture of diastereomers. Further deprotection steps are needed to complete the synthesis of 5. In summary, although the synthesis of the target compound 5 has not yet been accomplished,we already performed the most important steps for the assembly of 5, including insertion of the phosphate and phosphonate groups. Performance of deprotection steps on 28 will lead to the target compound 5, which is expected to serve as potent inhibitor of the enzyme.