Of monocyclic P-lactams

The synthesis of monocyclic p-lactams via the ester-enolate imine condensation route has been reported to be carried out utilizing triazene esters (Scheme 54), [141], Esters were attached to benzylamine resin by a triazene linker employing the respective diazonium salts. Immobilized ester-enolates were reacted with various imines to give polymer-bound p-lactams in different substitution patterns. Traceless cleavage from the triazene linker yielded the desired p-lactams. 

Scheme 54 Solid phase synthesis of monocyclic P-lactam derivatives...

The Staudinger reaction has been extensively studied for the synthesis of monocyclic p-lactams (Scheme 4, e.g., 19 and 20) [37]. An imine 18, a tertiary base (triethylamine), and acid chloride 17 (or equivalent) are required for this reaction. 

The ability to produce synthetic P-lactam antibiotics that have not come from fermentation is of considerable advantage industrially because microbiological spores are not present, negating the use of a dedicated contained plant. Evans and colleagues have described the synthesis of 1-carbacephalosporins (89), which are useful intermediates in the production of monocyclic P-lactam antibiotics.83 A significant step during this procedure is the conversion of an acylaminoazetidinone 90 to a P-keto ester 91 by ozonolysis (Scheme 11.24). 

The enthusiasm for the pharmaceutical potential of the monocyclic P-lactams was matched by renewed interest in the chemistry of these compounds both in industry and academe. This review will focus on recent developments in the chemistry of monocyclic P-lactam antibiotics, emphasizing new or improved methods for construction of the azetidinone ring as opposed to a discussion of the functional group manipulation of preformed P-lactams and the structure-activity relationships of the ultimate products. Emphasis will be placed on key advances in the preparation of true monocyclic antibiotics and intermediates for their synthesis and not on the voluminous chemistry dealing with the preparation of azetidinone intermediates for the synthesis of bicyclic compounds such as penems. The latter topic is covered elsewhere in this volume. The review is intended to cover the period from 1983 through early 1989 with an emphasis on more recent developments. Attention is drawn to previous reviews [4-14] which deal with the early phases of development of the monocyclic p-lactam antibiotics as well as those aspects of their chemistry not discussed in this work. 

There are indications [44] that the antibiotic properties of monocyclic P-lactams can be improved by placing an appropriate electron-withdrawing... 

Thomas, R.C. "Synthetic Aspects of Monocyclic P-Lactam Antibiotics" in Recent Progress in the Chemical Synthesis of Antibiotics G.Lukacs and M.Ohno Eds. Springer Verlag 1990 p 533. 

This methodology was also used to provide a synthesis of monocyclic P-lactams (26) in 70-90% yield [128] from a variety of imines (Scheme 54). However, replacing the ethyl bromoacetate by the corresponding 2-bromo-3-phenylpropionate did not give any P-lactam. Nevertheless,... 

SCHEME 3.15. Asymmetric solid-phase synthesis of monocyclic p-lactams. 

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