Smiths - -echinosporin synthesis

Smith s synthesis of (—)-echinosporin stands out for its good stereo-and regiocontrol at every stage. Its large number of highly chemoselective reactions, and its use of an asymmetric [2 + 2]-photocycloaddition reaction for constructing the m-fused 6,5-bicyclic core are also commendable. The latter reaction provides a beautiful illustration of how properly harnessed photochemistry can be decisively deployed for the stereocontrolled synthesis of complex natural products. 

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Mechanistic analysis of some key reactions employed in the Smith (—)-echinosporin synthesis... 

Echinosporin (XK-213) is a novel antitumour antibiotic isolated1 from the fermentation broths of Streptomyces echinosporus. It is of great pharmacological interest on account of its significant anticancer effects in several rodent tumour models. (—)-Echinosporin was recently synthesised in enantiomerically pure form by A.B. Smith and coworkers starting from L-ascorbic acid.2 Their synthesis is described below. 

Scheme 6.3 Smith s total synthesis of (-)-echinosporin from L-ascorbic acid.

Smith and co-workers utilized the Bamford-Stevens reaction en route to a total synthesis of echinosporin 51. Tosylhydrazone 49 was heated with sodium in ethylene glycol to afford key intermediate 50 on large scale. Dihydrofuran 50 was then taken through a further ten steps to afford echinosporin 51. 

Smith, A.B., III, Sulikowski, GA., Suhkowsld, M.M. and Fujimoto, K. (1992) Applications of an asymmetric [2+2]-phobxydoaddition total synthesis of (—)-echinosporin. Construction of an advanced 11-deo prostaglandin intermediate. Journal cf the American Chemical Society, 114, 2567-2576. 

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