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.     

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 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 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.     

Chemical synthesis of selenium-modified oligoribonucleotides and their enzymatic ligation leading to an U6 SnRNA stem-loop segment

The derivatization of nucleic acids with selenium is highly promising to facilitate nucleic acids structure determination by X-ray crystallography using the multiwavelength anomalous dispersion (MAD) technique. The foundation for such an approach has been laid by Huang, Egli, and co-workers and was exemplified on small DNA duplexes. Here, we present a comprehensive study on the preparation of RNAs containing 2'-Se-methylpyrimidine nucleoside labels. This includes the synthesis of a novel 2'-Se-methylcytidine phosphoramidite 11 and its incorporation into oligoribonucleotides by solid-phase synthesis. Deprotection of the oligonucleotides is achieved in the presence of millimolar amounts of threo-1,4-dimercapto-2,3-butandiol (DTT). With this additive, oxidation products and follow-up side-products are suppressed and acceptable HPLC traces of the crude material are obtained, so far tested for sequences of up to 22-mers. Moreover, an extensive investigation on the enzymatic ligation of the selenium-containing oligoribonucleotides demonstrates the high flexibility of the selenium approach. Our target sequence, an U6 snRNA stem-loop motif comprising all naturally occurring nucleoside modifications beside the Se-label is achieved by ligation using T4 RNA ligase.     

Studies on the synthesis of compounds related to adenosine 3',5'-cyclic phosphate. VII. Synthesis and cardiac effects of N6,N6-dialkyl adenosine 3',5'-cyclic phosphates

A series of novel N6,N6-dialkyl adenosine 3',5'-cyclic phosphates N6,N6-dialkyl cAMPs) was synthesized from 2'-O-p-toluenesulfonyl cAMP (2'-O-tosyl cAMP, 2) and tested for inotropic and chronotropic activities in vitro. Treatment of 2 with excess alkyl halides and sodium hydride followed by detosylation with aqueous NaOH readily gave N6,N6-dialkyl cAMPs (3) in good yields. Various N6,N6-dialkyl cAMPs having different alkyl groups at the N6-position (9-12) were prepared by alkylation followed by detosylation of N6-alkyl-2'-O-tosyl cAMPs (4) which were obtained by the reductive alkylation of 2 with aldehydes in the presence of sodium cyanoborohydride in acetic acid or tosylation of N6-methyl cAMP. The mechanism of the detosylation is briefly discussed. Among the N6,N6-dialkylated derivatives, N6,N6-dipentyl (3f) and N6-ethyl-N6-heptyl (10e) derivatives were found to exhibit a potent positive inotropic effect and a weak positive chronotropic effect. The structure-activity relationships for the position and the length of alkyl residue are discussed.     

Total synthesis of 2',3',4',5',5' '-(2)h(5)-ribonucleosides: the key building blocks for NMR structure elucidation of large RNA

The diastereospecific chemical syntheses of uridine-2',3',4',5',5' '-(2)H(5) (21a), adenosine-2',3',4',5',5' '-(2)H(5) (21b), cytidine-2',3',4',5',5' '-(2)H(5)(2)H(5) (21c), and guanosine-2',3',4',5',5' '-(2)H(5) (21d) (>97 atom % (2)H at C2', C3', C4', and C5'/C5' ') have been achieved for their use in the solution NMR structure determination of oligo-RNA by the Uppsala "NMR-window" concept (refs 4a-c, 5a, 6), in which a small (1)H segment is NMR-visible, while the rest is made NMR-invisible by incorporation of the deuterated blocks 21a-d. The deuterated ribonucleosides 21a-d have been prepared by the condensation of appropriately protected aglycone with 1-O-acetyl-2,3,5-tri-O-(4-toluoyl)-alpha/beta-D-ribofuranose-2,3,4,5,5'-(2)H(5) (19), which has been obtained via diastereospecific deuterium incorporation at the C2 center of appropriate D-ribose-(2)H(4) derivatives either through an oxidation-reduction-inversion sequence or a one-step deuterium-proton exchange in high overall yield (44% and 24%, respectively).     

Synthesis and Crystal Structure of 3′-Ethyl 5′-Methyl 1-Benzyl-4′-methyl-2-oxo-3′,4′-dihydrospiro-[indoline-3,2′-pyrrole]-3′,5′-dicarboxylate

The crystal structure of the title compound(C24H24N2O5, Mr = 420.45) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P1 with a = 8.991(1), b = 11.166(1), c = 11.169(1) , α = 91.413(2), β = 105.887(2), γ = 90.992(2)°, V = 1077.8(2) 3, Z = 2, Dc = 1.296 g/cm3, F(000) = 444, μ(MoKα) = 0.091 mm-1, the final R = 0.0466 and wR = 0.1507 for 4185 observed reflections(I 2σ(I)). The single-crystal X-ray diffraction data indicated intermolecular C(17)–H(17)O(4), C(5)–H(5)… O(4) hydrogen bonds and C–H…π interaction in the structure.     

3-(2'-苯基-1', 2', 3'-连三唑-4'-基)-6-烷基/芳基-均三唑并[3, 4-b]-1, 3, 4-噻二唑的合成

研究了3-(2'-苯基-1', 2', 3'-连三唑-4'-基)-4-氨基-5-巯基-1, 2, 4-三唑(1)与取代苯甲酸和脂肪酸(2a-r)在POCl3催化下的反应, 共合成得到18个新的3-(2'-苯基-1', 2', 3'-连三唑-4'-基)-6-烷基/芳基-均三唑并[3, 4-b]-1, 3, 4-噻二唑(3a-r), 经元素分析,IR, 1H NMR和MS进行了结构确证。     

Synthesis of 5, 7-dimethylthieno-, 3, 1-dimethylthionaphtheno-, and 6, 4-dimethylthienothienopyridines

New heterocyclic compounds with a condensed thiophene ring are synthesized.     

Chemical Synthesis of a 5'-Terminal TMG-Capped Triribonucleotide m(3)(2,2,7)G(5)(')pppAmpUmpA of U1 RNA

The 5'-terminal TMG-capped triribonucleotide, m(3)(2,2,7)G(5)(')pppAmpUmpA, has been synthesized by condensation of an appropriately protected triribonucleotide derivative of ppAmpUmpA with a new TMG-capping reagent. During this total synthesis, it was found that the regioselective 2'-O-methylation of 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-N-(4-monomethoxytrityl)adenosine was achieved by use of MeI/Ag(2)O without affecting the base moiety. A new route to 2-N,2-N-dimethylguanosine from guanosine via a three-step reaction has also been developed by reductive methylation using paraformaldehyde and sodium cyanoborohydride. These key intermediates were used as starting materials for the construction of a fully protected derivative of pAmpUmpA and a TMG-capping reagent of Im-pm(3)(2,2,7)G. The target TMG-capped tetramer, m(3)(2,2,7)G(5)(')pppAmpUmpA, was synthesized by condensation of a partially protected triribonucleotide 5'-terminal diphosphate species, ppA(MMTr)mpUmpA, with Im-pm(3)(2,2,7)G followed by treatment with 80% acetic acid. The structure of m(3)(2,2,7)G(5)(')pppAmpUmpA was characterized by (1)H and (31)P NMR spectroscopy as well as enzymatic assay using snake venom phosphodiesterase, calf intestinal phosphatase, and nuclease P1.     

3-(2-卓二唑啉基) - 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-卓二唑啉基)-色酮(5a～5o),并通过元素分析,IR,^1^HNMR和MS谱数据确证了上述化合物的结构。     

Synthesis of 5, 7-dimethylthieno-, 3, 1-dimethylthionaphtheno-, and 6, 4-dimethylthienothienopyridines

New heterocyclic compounds with a condensed thiophene ring are synthesized.     

三组分一锅法合成3-甲基-1-苯基-4-芳基-4,11-二氢-4H-吡唑并[4',5':3,2]吡啶并[5,6-c]香豆素

以芳醛、4-羟基香豆素和3-甲基-1-苯基-5-氨基吡唑为原料,用少量冰醋酸作溶剂,三组分一锅法合成一系列吡唑并[4',5':3,2]吡啶并[5,6-c]香豆素衍生物,该反应产率高(79%～94%)、操作简单、后处理方便.产物的结构经红外光谱、核磁共振氢谱、元素分析及单晶X射线分析证实.     

5-取代苯胺基-6-苯基-1, 2, 4-三嗪-3-硫酮的合成

苯甲酰基-N-取代苯基硫代甲酰胺和氨基硫脲反应, 首先在酸性介质中形成缩氨基硫脲, 然后在碱性介质(pH=8~9)中环化, 生成5-取代苯胺基-6-苯基-1, 2, 4-三嗪-3-硫酮。本文合成10个新的该类杂环化合物。