Synthesis of New Statin Derivatives

Herein we report the synthesis of the new statin derivative MC609 in 80 % overall yield by sequential transformation of simvastatin including dehydration, and Michael addition of N-benzyl hydroxylamine followed by cyclization. The preparation of nitronestatins MC649 and MC645 is also described from (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-6-oxotetrahydro-2H-pyran-2-carbaldehyde by reaction with N-benzyl hydroxylamine, and N-hydroxylamine followed by reduction with sodium cyanoborohydride and coupling with commercially available 2-chloro-6-methylquinoline-3-carbaldehyde, in 77 % and 24 % overall yield, respectively.

Automated summary

The new statin derivative MC609 and nitronestatins MC649 and MC645 were synthesized in overall yields of 80%, 77%, and 24% respectively. Different synthetic pathways were employed, including dehydration, Michael addition, reduction, and coupling reactions.