Stereoselective synthesis of deoxy analogues of the 3C-protease inhibitor thysanone

The synthesis of racemic 7,9-dideoxythysanone 9 was achieved starting from allyinaphthalene 5 via epoxidation and reduction to bromoalcohol 7. Subsequent lithiation of the bromide and quenching with DMF afforded lactol 8 which underwent clean oxidative demethylation to racemic 6,8-dideoxythysanone 9. The synthesis of (1R,3S)-(+)-7,9-dideoxythysanone 9 was then achieved albeit in low ee, starting from (R)-epoxide 6 which in turn was obtained via Sharpless asymmetric dihydroxylation of allylnaphthalene 5. An improved asymmetric synthesis of (IS,3R)-(+)-7,9-dideoxythysanone 9 in 72% ee was then accomplished starting from (R)-bromoalcohol 7 which was obtained via asymmetric reduction of ketone 12 using a modified chiral oxazaborolidine. The key ketone 12 in turn was prepared by Wacker oxidation of allylnaphthalene 5. (C) 2002 Elsevier Science Ltd. All rights reserved.