Cephalosporin 3-nitrogen-substituted

The only complete synthesis of cephalosporin C provides a classic example of the synthetic art of the late R. B. Woodward, and formed the subject of his Nobel Prize winning lecture of 1965. The synthesis, published in 1966, starts from L(+)-cysteine (189) 164, 165). Protection of the nitrogen, sulphur and acid functional groups provided the cyclic intermediate (191) ideally suited for the introduction of the amino function which was to become the nitrogen atom of the crucial -lactam intermediate (195). This was achieved in a completely stereocontrolled manner by a novel substitution method. Thermal introduction of the hydrazo-substituent to form (192) was followed by oxidation and conversion to the tran -hydroxy ester (193). Inversion by displacement of the mesylate with azide and subsequent reduction gave the cw-amino ester (194) which afforded the (i-lactam (195) on cyclisation. 

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