Organocatalyzed synthesis of carbapenem β-lactam cores and monobactam.

Abstract

Organocatalysis has emerged as a new powerful methodology for the catalytic production of enantiomerically pure organic compounds. The main aim of this work was to develop organocatalyzed routes to novel β-lactam derivatives. In chapter 2, the first organocatalyzed C-C bond forming reactions have been performed on the carbapenem core 1, was the Aldol reaction, with various aldehydes to afford the corresponding products in good yields (up to 76%) and excellent diastereoselectivities (up to 99:1 ratios). Next, the Mannich reaction was evaluated with different amines and aldehydes. The products were obtained with modest chemical efficiency (up to 55%) and excellent diastereoselectivities (up to 99:1 ratios) as with the Aldol reaction. The reactivity of the carbapenem core 1 was also evaluated in the Michael addition reaction with electrophilic olefins. Chapter 3 includes the full substrate scope of organocatalytic asymmetric Michael addition transformations on the carbapenem core 1 reported. Good yields (up to 67%) and some excellent diastereoselectivities (up to 92:8 ratios) were obtained with L-proline as the organocatalyst. We have also demonstrated the possibility to effectively convert the Michael products to monobactams through a retro-Dieckmann reaction under basic conditions, thereby leading to another highly valued class of β-lactam antibiotics. Chapter 4 is the summary of the thesis.