Stereoselective Formation of a β-Lactam Fused Oxathiazepin: A Synthetic Approach to Eudistomins

Abstract

A synthetic approach to eudistomin via a β-lactam fused bicyclic oxathiazepin intermediate is described. A β-lactam fused oxathiazepin derivative was synthesized by intramolecular 7-membered oxime ether formation and subsequent face-selective reduction of the C-N double bond. A fully functionalized ortho-alkenylphenylthioanilide bearing oxathiazepin ring was then prepared and construction of the indole skeleton under several radical-mediated conditions was examined.

Key words

eudistomin - bicyclic β-lactam - oxathiazepin - 2,3-di­substituted indole - radical cyclization

References

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10

Optically active β-lactam 10 could be prepared using glyceraldehyde as a chiral template. [9a]

11

Choice of solvent (protic or aprotic) was quite important for this reduction. When oxime ether 17 was reduced with NaBH₄ in MeOH, an ca. 1:1 mixture of the hemiaminal 25 and the desired product 26 was obtained (Figure [2] ).

Figure 2 Structures of 17, 25, and 26