Synthesis of 2',3'-dideoxy-2'-trifluoromethylnucleosides from alpha-trifluoromethyl-alpha,beta-unsaturated ester

The treatment of alpha-bromo-alpha,beta-unsaturated esters 2 with FSO(2)CF(2)CO(2)Me and CuI in DMF/HMPA constitutes a new synthetic scheme for the preparation of alpha-trifluoromethyl-alpha, beta-unsaturated esters 3. The trifluoromethylation of (Z)/(E)-ethyl 3-[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-bromo-2-propenoate (2e), which is derived from 1-(R)-glyceraldehyde acetonide, yields the key intermediate alpha-trifluoromethyl-alpha,beta-unsaturated esters 3e. This is transformed into anomeric acetates 8a and 8b and is used for the synthesis of a number of 2', 3'-dideoxy-2'-trifluoromethylnucleosides.     

Synthesis of 3'-fluoro-2',3'-dideoxy-2',3'-didehydro-4'-ethynyl-D- and -L-furanosyl nucleosides

An efficient procedure has been developed for the synthesis of 3'-fluoro-2',3'-dideoxy-2',3'-didehydro-4'-ethynyl D- and L-furanosyl nucleosides (1 and 2) starting from 2,3-O-isopropylidene-d-glyceraldehyde. The key intermediate 1-O-benzoyl-3E-fluoro-3,4-unsaturated-5,6-di(tert-butyldimethylsilyloxy)-2-hexanone 8 was obtained in nine steps with the overall yield of 22%. The alpha,beta-unsaturated ketone 8 was then treated with ethynylmagnesium bromide in a typical Grignard reaction procedure to afford the two intermediates 9 and 10, which after deprotection, oxidation, and acetylation gave the corresponding 4-ethynyl-substituted D- and L-sugar moieties 15 and 16, respectively. A series of D- and L-pyrimidine and purine nucleosides were prepared by the coupling of the sugar moieties with various silylprotected bases. The anomeric mixtures were obtained after condensation. After separation, the beta-isomers were further deprotected to yield the target nucleosides. All the newly synthesized 4'-substituted nucleosides were tested for their activities against HIV, among which the D-adenine derivative showed moderate anti-HIV activity (EC(50) = 25.1 microM) without significant cytotoxicity.     

Stereoselective synthesis and conformational study of novel 2',3'-Didehydro-2',3'-dideoxy-4'-selenonucleosides

Stereoselective synthesis of novel 2',3'-didehydro-2',3'-dideoxy-4'-selenonucleosides (4'-seleno-d4Ns) 4a- c was accomplished via 4'-selenoribofuranosyl pyrimidines 11a- c, as key intermediates. 4'-Selenoribofuranosyl pyrimidines 11a- c were efficiently synthesized from d-ribose or d-gulonic gamma-lactone using a Pummerer-type condensation as a key step. Introduction of 2',3'-double bond was achieved by treating cyclic 2',3'-thiocarbonate with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine.     

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.     

Enantiomeric syntheses of conformationally restricted D- and L-2', 3'-dideoxy-2',3'-endo-methylene nucleosides from carbohydrate chiral templates

D- and L-2',3'-dideoxy-2',3'-endo-methylene nucleosides were synthesized as potential antiviral agents. The key intermediates 5-O-tert-butyldiphenylsilyl-D- and L-2,3-dideoxy-2, 3-endo-methylenepentofuranoses (20 and 33, respectively) were obtained by selective protection of the D- and L-2,3-dideoxy-2, 3-endo-methylenepentose derivatives 19 and 32 which were prepared from 1,2:5,6-di-O-isopropylidene-D-mannitol and L-gulonic gamma-lactone, respectively, and converted to 5-O-tert-butyldiphenylsilyl-D- and L-2,3-dideoxy-2, 3-endo-methylenepentofuranosyl acetates (21 and 34, respectively) or the chlorides 22 and 35. The acetates and chlorides were condensed with pyrimidine and purine bases by Vorbrüggen conditions or S(N)2-type condensation. Vorbrüggen conditions using the acetates gave mostly alpha-isomers. In contrast, S(N)2-type condensation using the chlorides greatly improved the beta/alpha ratio. From the synthesis, several D- and L-2',3'-dideoxy-2',3'-endo-methylene nucleoside analogues have been obtained, and their structures have been elucidated by NMR spectroscopy and X-ray crystallography. The synthesized D- and L-adenine derivatives were tested as substrates of adenosine deaminase, which indicated that the D-adenosine derivative 4a was a good substrate of a mammalian adenosine deaminase from calf intestinal mucosa (EC 3.5.4.4) while its L-enantiomer 10a was a poor substrate. Either the D-adenine derivative 4a or its L-enantiomer 10a did not serve as an inhibitor of the enzyme.     

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.     

Synthesis of 3',3'-difluoro-2'- hydroxymethyl-4',5'-unsaturated carbocyclic nucleosides

3',3'-Difluoro-2'-hydroxymethyl-4',5'-unsaturated carbocyclic nucleosides 1-3 have been stereoselectively synthesized from ester 10, which can be conveniently prepared from 2,3-isopropylidene-d-glyceraldehyde 7 in five steps. The whole synthesis highlighted the stereoselective Reformatskii-Claisen rearrangement, ring-closing metathesis (RCM), and palladium-catalyzed allylic alkylation, in which the regioselectivity was reversed from that of nonfluorinated substrates.     

Synthesis and mesomorphic properties of 4-methoxyphenyl 4'- n -alkoxy-2',3',5',6'-tetrafluorobiphenyl-1-carboxylates

A novel type of 4-methoxyphenyl 4'- n -alkoxy-2',3',5',6'-tetrafluorobiphenyl-1-carboxylates have been synthesized. Textural observations by polarizing microscopy and DSC measurements of the phase transitions show that all of these compounds are thermotropic liquid crystals with only a nematic mesophase. The relationship between the properties and chemical structures of these compounds is discussed.     

3-(2-二唑啉基)-色酮类化合物的合成研究

报道了取代的邻羟基苯乙酮(1a～1e)经Vilsmeier-Haack反应一步制得3-醛基色酮(2a～2e),2a～2e与取代的芳酰肼(3a～3c)缩合制得15个酰腙类化合物(4a～4o),4a～4o在醋酸酐作用下关环得15个3-(2-苝二唑啉基)-色酮(5a～5o),并通过元素分析,IR,~1H NMR和MS诺数据确证了上述化合物的结构。     

2',5'-二氢-1'H-吡咯骈[3',4':1,2][60]富勒烯衍生物的合成

以甘氨酸乙酯盐酸与取代的苯甲醛为原料,制得了一系列亚胺,然后用亚胺与C~6~0反应,得到带有不同取代基的吡咯烷骈[60]富勒烯衍生物.经^1HNMR,^1^3CNMR,FT-IR,UV-vis以及TOF-SMS等方法对所得化合物结构进行了表征,并进行了产物的生物活性测试。     

Efficient synthesis of 2',3'-dideoxy-2'-amino-3'-thiouridine

[reaction: see text] Metal ion rescue experiments provide a powerful approach to establish the presence and role of divalent metal ions in the biological function of RNA. The utility of this approach depends on the availability of suitable nucleoside analogues. To expand the range of this experimental strategy, we describe the first synthesis of 2',3'-dideoxy-2'-amino-3'-thiouridine (12) in 19.5% overall yield starting from 2,2'-anhydrouridine (1).     

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…