Recent Approaches Toward Solid Phase Synthesis of β-Lactams

Abstract

Since the discovery of penicillin in 1929, b-lactam antibiotics have been recognized as potentially chemotherapeutic drugs of incomparable effectiveness, conjugating a broad spectrum of activity with very low toxicity. The primary motif azetidin-2-one ring (b-lactam) has been considered as specific pharmacophores and scaffolds. With the advent of combinatorial chemistry and automated parallel synthesis coupled with ample interests from the pharmaceutical industries, recent trends have been driven mostly by adopting solid phase techniques and polymersupported synthesis of b-lactams. The present survey will present an overview of the developments on the polymer-supported and solid phase techniques for the preparation of b-lactam ring or b-lactam containing antibiotics published over the last decade. Both unsubstituted and substitutions with different functional groups at various positions of b-lactams have been synthesized using solid phase technology. However, Wang resin and application of Staudinger [2+2] cycloaddition reaction have remained hitherto the major choice. It may be expected that other solid phase approaches involving different resins would be developed in the coming years.

Microwave-induced ferrier rearrangement of hyroxy beta-lactams with glycals

“…Many crucial procedures are available for the synthesis of beta-lactams [28] . These include Staudinger cycloaddition method [17,[29][30][31] , ester enolate-imine condensation [32,33] , hydroxamate reaction [34] , alkene-isocyanate procedure [35] , and the alkyne-nitrone method [36,37] , Catalytic asymmetric [38,39] and polymer-supported [40,41] preparation of beta-lactams are also achieved. intermediate present in the side chain of Taxol and Taxotere [12][13][14] .…”

Stereoselective Cycloaddition Reactions

“…These reactions proceed in a concerted mechanism with a high degree of regio-and stereoselectivity. [5][6][7][8] This review, in particular, summarizes stereoselective cycloaddition reactions and their solid-phase versions carried out on polymer supports for the synthesis of natural products and their analogs, focusing on the reactions that were employed as key steps. Based on the p-electron systems of reactants, they can be further classified into [4 þ 2], [3 þ 2], and [2 þ 2] cycloadditions that produce six-, five-, and fourmembered rings, respectively.…”

Synthesis of Multicyclic β-Lactam Derivatives via Solid-Phase-Generated Ketenes

“…In conclusion, it is well-known the biological importance of bicyclic β-lactams, which include penicillins, cefalosporins, penems, carbapenems, carbacephems, oxacephems, and clavams, among other structures. Despite their undoubted significance, very few solid-phase methods have been reported in literature for the construction of multicyclic β-lactam systems; actually, most of the procedures are related to the preparation of monocyclic β-lactams (monobactams) . Now, we are extending the scope of these methodologies by adding an efficient synthetic sequence for the solid-phase preparation of multicyclic β-lactam derivatives.…”