ENANTIOSPECIFIC TOTAL SYNTHESIS OF L-2',3'-DIDEOXYISONUCLEOSIDES VIA REGIOSELECTIVE OPENING OF OPTICALLY-ACTIVE C-2-SYMMETRICAL 1,4-PENTADIENE BIS-EPOXIDE

A new method for the synthesis of L-2',3'-dideoxyisonucleosides is des cribed. The readily available, optically active C-2-symmetric bis-epox ide (2S,4S)-1,2:4,5-diepoxypentane (5) was prepared by a short route f rom readily available starting materials. The key step of the new synt hesis is the opening of 5 with nucleophiles, which proceeds highly reg ioselectively; e.g., reaction with sodium sulfide affords a 5:1 mixtur e of the tetrahydrothiophenediol 9a and the tetrahydrothiopyrandiol 14 , and reaction with sodium hydroxide gives exclusively the tetrahydrof urandiol 9b via a preferred 5-exo cyclization. These five-membered dio ls 9a,b can be converted in only four steps into the modified dideoxyu ridine and adenosine isonucleosides 4a-c, one of which (4c) has shown good antiviral activity. In addition, we have examined the opening of the analogous six carbon bis-epoxide, (2S,5S)-1,2:5,6-diepoxyhexane (2 3), which affords a 3:1 mixture of the hexahydrothiepinediol 24 and th e tetrahydrothiopyrandiol 25 with sodium sulfide via a preferred 7-end o cyclization. An alternate route to these two optically active bis-ep oxides 5 and 23 was also examined, namely the asymmetric dihydroxylati on of 1,4-pentadiene and 1,5-hexadiene followed by selective sulfonyla tion and epoxide : formation. The asymmetric reaction produces a nearl y 1:1 mixture of optically active and meso tetrols, e.g., 28-9 and 32- 3. Unfortunately, the tetrols, their simple derivatives, and the final sulfonates and epoxides could not be readily separated by Rnv simple means.