Improved Synthesis of (-)-Agelastatin A.

Optimization of key steps in the synthesis of the architecturally unique tetracyclic antitumor alkaloid (-)-agelastatin A (1) improved the overall yield of the 11-step process (eight operations) from 9% to 23%. Changing the solvent and using a more efficient N-benzyl deprotecting-group procedure enhanced the yields of the C-ring and D-ring intermediates, (-)-4 and (-)-7, respectively. Bromination of (-)-7 with 1,3-dibromo-5,5-dimethylhydantoin, rather than N-bromosuccinimide (NBS), increased the yield of (-)-1 from 69% to more than 94% yield. [ABSTRACT FROM AUTHOR]