Synthesis of 2',3'-dideoxy-6',6'-difluorocarbocyclic nucleosides

2',3'-Dideoxy-6',6'-difluorouracils, a novel series of gem-difluoromethylenated carbocyclic nucleosides, were synthesized from (Z)-but-2-ene-1,4-diol in 14 steps. A notable step was the construction of the carbocyclic ring via ring-closing metathesis and the incorporation of gem-difluoromethylene group by way of silicon-induced Reformatskii-Claisen reaction of chlorodifluoroacetic ester 3.     

Synthesis of Novel Nucleoside: 2'-deoxyuridine-3',5'-di(4, 4'-dimethoxy-5, 6, 5', 6'-dimethylenedioxybipheny1-2-methoxy carbonyl 2'-carboxylate)

Anumberofnucleosideshavebeenreportedtobeanti-hepatitisBvirusagents',althoughnoneofthemhaveyetbeenprovedtobeclinicallyusefull.Inaddition,dimethyldicarboxylatebiphenyl(DDB)isawidelyusedanti-hepatiticdrugwithhigheffectinloweringSGPTandconsiderablelowtoxicity'.InviewofthediscoverythatseveralnucleosideswiththeD-configurationandanaloguesofthebiphenyldicarboxylateareselectiveantiviralagents,itwasofinteresttosynthesizenucleosidederivativesaspotentialantiviralagents.Recently,thecarbocyclicanalogueo…     

Synthesis of Conformationally Locked 2＇-Deoxy-2＇-nucleobase-5＇- Isonucleosides: 2＇-Deoxy-2＇-nucleobase-5＇ deoxy-1＇, 4＇ :3＇, 6＇-dianhydro-D-mannitol

Novel bicyclic isonucleosides, 2＇ -deoxy- 2＇ -nucleobase- 5＇ -deoxy- 1＇ , 4＇ : 3＇ , 6＇ -dianhydro D-mannitol 10a-10c, were synthesized from D-glucose. The computer-assisted molecular simu lation indicated that the sugar conformations of compounds 10a-10c were restricted to N-con formation.     

Synthesis of Conformationally Locked Isonucleosides: 2'-Deoxy-2'-nucleobase-5'- deoxy-1', 4' : 3' , 6'-dianhydro-D-mannitol

IntroductionA novel class of nucleoside analogues, termed conformationa1ly locked nucleosides, hasattracted much attention owing to their conformationally restricted structures and their potentbiological activities. Griseolutic acids(I ), a family of naturally occurring bicyclic nucleosides,were isolated from StrePtomyces grisroaurantiacus and showed the inhibitory activities againstc--AMP phosphodiesterase and were able to induce the differentiation of murine neuroblas-tomaLl3. A large num…     

Synthesis of new 2',3'-dideoxy-6',6'-difluoro-3'-thionucleoside from gem-difluorohomoallyl alcohol

[reaction: see text] 2',3'-Dideoxy-6',6'-difluoro-3'-thionucleoside 1b, an analogue of 3Tc that has high biological activities against HIV and HBV, has been synthesized from gem-difluorohomoallyl alcohol 3 in an efficient way. The key intermediate 4-amino-3,3-difluorotetrahydrothiophen-2-ylmethyl benzoate 15 was prepared from 2,2-difluoro-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]but-3-en-1-ol 3 in 11 steps. The construction of pyrimidine ring with the amino group of compound 15 gave the target compound 1.