A Stereoselective Anti-Aldol Route to (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol: A Key Ligand for a New Generation of HIV Protease Inhibitors

Abstract

A stereoselective synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol, an important high affinity P₂-ligand, in high enantiomeric excess (>99%) is reported. The synthesis features an ester-derived titanium enolate based highly stereoselective anti-aldol reaction as the key step.

Key Words

antiviral agents - asymmetric synthesis - chiral auxiliary - aldol reactions - fused-ring systems

References

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On June 23, 2006, the FDA approved a new HIV treatment for patients who do not respond to existing drugs; see: www.fda.gov/bbs/topics/NEWS/2006/NEW01395.html.

12

The Mosher ester was formed by the reaction of Mosher acid and alcohol 3 with EDCI in the presence of DMAP. The ¹⁹F NMR analysis of the Mosher ester¹³ revealed an enantiomeric purity of >99%.