The Beta-lactam antibiotics are a large family of natural and semi-synthetic compounds of clinical importancae. This proposal presents a flexible new synthetic approach to these compounds with an emphasis on the carbapenem family of Beta-lactams. The approach relies on the development of stereoselective ester-imine condensations as potent method for preparing the Beta-lactam nucleus. The development of N-trimethylsilyl and relataed imines as electrophilic N-protio imine equivalents play a central role in this process. The route is designed such that derivatives of other Beta-lactam antibiotics, such as the norcardicins and monobactams, could be prepared using the same technology. The application of ester-imine condensations to the synthesis of natural products containing vicinal diamine substructures, such as the vitamin biotin, is also discussed. A stereochemical study of reactions between allylic organometallics and azomethines is also proposed. The application of these reactions to the synthesis of two Alpha-amino acid enzyme antagonists is presented. A new enantioselective approach to Alpha-amino acid synthesis via SN2' reactions using menthone as a chiral template is also described.
| Ha, D C; Hart, D J (1987) Ester-imine condensations: preparation of racemic intermediates for the synthesis of the carbapenem antibiotics PS-5 and PS-6. J Antibiot (Tokyo) 40:309-19 |
