Total Synthesis of Penicillins and Cephalosporins

Major advances have been achieved in the total syntheses of penicillins, cephalosporins, and related nuclear analogues in recent years. Although a number of synthetic approaches are under scrutiny, thus far, the Merck keten-imine approach and its many variants have produced the most promising results. However, the classical Sheehan synthesis, the Lowe diazo-amide photolysis approach, and a novel biogenetic-type synthesis have been utilized with success. 

A similar route was employed by workers at the Syntex Laboratories to prepare the lactone (147). Cycloaddition of azidoacetyl chloride to the furanothiazine 

Reagents i, Mel ii, NaCHaCOCl-EtsN iii, CU iv, HOCHaCOCHaOAc-AgBF v, NaH-DME vi, separate the isomers vii, Hj-Pd/C viii, thienylacetyl chloride 

Organic Compounds of Sulphury Selenium, and Tellurium Phth H 

Reagents i, PhthCH,COCI ii, sulphur deblocking iii, Mel-Nal-DMF, HgCI iv, DMSO 

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Heusler, K. Total Synthesis of Penicillins and Cephalosporins in reference 6, pp. 255-279. 

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