合成路线1

Other methods based on the modification of carbohydrates have also been described: 7) Protection of readily available (S)-(+)-gamma-(hydroxymethyl)-gamma-butyrolactone (XIX) with tert-butyldiphenylsilyl chloride gives ether (XX), which is converted to the seleno derivative (XXI) on treatment with lithium hexamethyldisilazide and trimethylchlorosilane in tetrahydrofuran, followed by reaction with phenylselenylbromide. Reduction of (XXI) with diisobutylaluminum hydride in toluene followed by acetylation gives compound (XXII), which is reacted with (XXIII) and trimethylsilyltriflate in dichloroethane to afford stereoselectively compound (XXIV). The latter is finally submitted to elimination and deprotected by successive treatment with hydrogen peroxide in pyridine and tetrabutylammonium fluoride in tetrahydrofuran. 8) A related route involves treatment of (XX) with lithium diisopropylamide in tetrahydrofuran and diphenylsulfide in HMPA to give (XXV), which is reduced and acetylated to yield (XXVI). Compound (XXVI) is treated with (XXIII) in the presence of tin tetrachloride in dichloromethane to afford (XXVII), which is oxidized with sodium periodate and submitted to elimination by treating in toluene-pyridine, to yield compound (XXVIII). Finally, compound (XXVIII) is deprotected with tetrabutylammonium fluoride in tetrahydrofuran. 9) A third procedure begins with the protection of (XIX) as a tert-butoxycarbonyl ester to yield (XXIX), reduction with diisobutylaluminum hydride in tetrahydrofuran to afford (XXX) and elimination after treatment with thionyl chloride in dichloromethane and potassium tert-butoxide in tetrahydrofuran to give (XXXI). Subsequent reaction of compound (XXXI) with thymine (IX) in the presence of hexamethyldisilazane and trimethylsilyl chloride and N-chlorosuccinimide in tetrahydrofuran gives compound (XXXII), which is treated with potassium tert-butoxide in tetrahydrofuran and deprotected with sodium methoxide in methanol.