This research program is dedicated to developing new techniques and chiral agents for the control of absolute stereochemistry. This multifaceted program combines significant activities in the following areas that follow a logical developmental flow from achievements during the previous granting period, including: 1) design and construction of new chiral auxiliaries; 2) development of new methods for asymmetric induction using current and new auxiliaries in both stoichiomehic and catalytic processes; 3) application of techniques for control of absolute stereochemistry to the synthesis of relatively small but significant target molecules. The stereochemical purity of materials that are tested and ultimately used as biochemical mediators has become an important criterion as it is now fully appreciated that changes in stereochemistry are often associated with dramatically altered biological responses. The methods developed under this program have a wide range of applications to the efficient laboratory preparation of stereochemically, and especially enantiomerically pure materials. These techniques will be of value at all stages of pharmaceutical development: from providing access to materials for evaluation that were unavailable by previous methods to providing commercially viable routes for the preparation of large quantities. All three of the stated objectives of this program given above have been met in the previous granting period, and sufficient ongoing, positive results are available to guarantee success in future years.
| Lynch, V M; Yaser, H K; Whitesell, J K et al. (1991) The structure at 198 K of (1R,5R,15R,16R)-5-isopropenyl-2-methyl- 1-[N-(trans-2-phenylcyclohexyloxycarbonyl)amino]-2-cyclohexene. Acta Crystallogr C 47 ( Pt 7):1566-8 |
| Whitesell, J K; Lawrence, R M (1989) Stereocontrolled synthesis of peptide bond isosteres. Chirality 1:89-91 |
