Manganese Dioxide Mediated Stereoselective, One-step Synthesis of Novel Steroidal (6R)-Spiro-1’,2’,4’-triazoline-3’-thiones

Oxidative cyclization of 5α-cholestan-6-one thiosemicarbazone (1), its 3β-chloro (2) and 3β-acetoxy (3) analogues with active manganese dioxide at room temperature afforded selectively the corresponding (6R)-spiro-1’,2’,4’-triazoline-3’-thiones 4—6. This synthesis has the advantages of mild reaction conditions, easy handling, easily available reagent and high yields. The products have been characterized by analytical and spectral data.     

Synthesis and Antibacterial Activity of 8-Substituted Phenyl-1-pyridin-3-yl-5H-bis[1, 2, 4]triazolo[3, 4-b； 4＇, 3＇-d][1, 3, 4] thiadiazines

To find new structural leading compounds for the research of the multidrug resistant of antibacterial agents, five novel 8-substituted phenyl-l-pyridin-3-yl-5H-bis[1, 2, 4] triazolo[3, 4-b;4‘,3‘-d] thiadiazines were prepared from the corresponding intermediates of 3-(5-substituted phenyl[1,3,4]oxadiazol-2-ylmethylsulfanyl)-5-pyridin-3-yl-[1,2,4]triazol-4-ylamines via intramolecular cyclization and the antibacterial activity in vitro against Gram-postive (G^ ) and Gramnegatiye (G) bacteria was primarily evaluated.     

Phase Transfer Catalyzed Synthesis of 1, 2-Bis[（3-aryl）-s-triazolo- [3, 4-b]-[1, 3, 4]thiadiazole-6-yl]ethanes

s-Triazolo[3, 4-b]-[1, 3, 4]thiadiazole derivatives have been paid attractive attention due to their significantly biological activities1-5, including antibacterial, antifungal, anticancer, relaxing vascular activities. They are highly important heterocyc…     

Novel Synthesis and Characterization of N‐Substituted‐calix[4]azacrown Derivatives

Novel calix[4]azacrown derivatives from the reaction between calix[4]amidocrown and the different N‐(4‐bromoacetamidephthalimido)alkanes derivatives, which may be useful intemediate compounds of pseudorotaxane, have been synthesized and structurally characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analyses. From their analysis data, it was found that compounds 6a–d adopted a cone conformation.     

Pyridine-2(1H)-thione in Heterocyclic Synthesis: Synthesis of Some New Nicotinic Acid Ester,Thieno[2, 3-b]pyridine,Pyrido[3′, 2′: 4, 5]thieno [3, 2-d]pyrimidine,and Thiazolylpyrazolo[3, 4-b]pyridine Derivatives

Nicotinic acid esters 3a–c were prepared by the reaction of pyridine-2(1H)-thione derivative 1 with α-halo-reagents 2a–c. Compounds 3a–c underwent cyclization to the corresponding thieno[2, 3-b]pyridines 4a–c via boiling in ethanol/piperidine solution. Compounds 4a–c condensed with dimethylformamide-dimethylacetal (DMF-DMA) to afford 3-{[(N,N-dimethylamino)methylene]amino}thieno[2, 3-b]- pyridine derivatives 6a–c. Moreover, compounds 4a–c and 6a–c reacted with different reagents and afforded the pyrido[3′,2′:4, 5]thieno[3, 2-d]pyrimidine derivatives 10a–d, 11a–c, 12a,b, 14a,b, 17, and 19. In addition, pyrazolo[3, 4-b]pyridine derivative 20 (formed via the reaction of 1 with hydrazine hydrate) reacted with ethylisothiocyanate yielded the thiourea derivative 21. Compound 21 reacted with α-halocarbonyl compounds to give the 3-[(3H-thiazol-2-ylidene)amino]-1H-pyrazolo[3, 4-b]pyridine derivatives 23a–c, 25, and 27a,b.     

Synthesis of Some Novel Fluorinated Pyrazolo[3,4‐b]Pyridines

Abstract

Reaction of 5‐amino‐3‐substituted pyrazoles (1a–c) and 5‐amino‐1,3‐disubstituted pyrazoles (1d–i) with fluorinated‐β‐diketones (2) results in the formation of the single isomer of pyrazolo[3,4‐b]pyridines (4a–h). A one‐pot procedure for the synthesis of title compounds starting from α‐cyanoacetophenones along with a possible mechanistic pathway for the formation of the title compounds is described.     

Synthesis of Some New Thieno[2,3-b]pyridines,Pyrimidino[4′,5′:4,5]thieno[2,3-b]-pyridines,and 2,3-Dihydro-1,3,4-thiadiazoles

Thieno[2,3-b]pyridines were synthesized from 6-benzofuran-2-yl-4-phenyl-2-sulfanylpyridine-3-carbonitrile and each of chloro acetone, ethyl chloroacetate, ω -bromoacetophenone, and chloroacetonitrile. These compounds were conveniently converted into novel pyrido[4′,5′:4,5]thieno[3,2-d]pyrimidines. Also, 2,3-dihydro-1,3,4-thiadiazole was synthesized from hydrazonoyl halides and 2-benzofuran-2-yl-3-(phenylamino)-3-thioxopropanenitrile. The structures of the products have been elucidated by elemental analyses, spectral data studies, and alternative syntheses whenever possible. The newly synthesized compounds were tested towards microorganisms.     

Synthesis and Quantum Chemistry Study of Novel Bifurazano [3,4-b : 3′, 4′-f] furoxano [3″, 4″-d] oxacyclohetpatriene

以3,4-双(4′-硝基呋咱-3′-基)氧化呋咱为原料,设计并合成了新型双呋咱并[3,4-b∶3′,4′-f]氧化呋咱并[3″,4″-d]氧杂环庚三烯(1),收率50.1％,其结构经13C NMR,15N NMR,IR,MS和元素分析表征.最佳的反应条件为:以无水碳酸钠为催化剂,乙腈(含水量0.04％)为溶剂,于80℃反应3.5h.用B3LYP方法在6-31G**基组水平上对1的结构进行了计算,得到了稳定的几何构型和键级.在振动分析的基础上求得体系在不同温度下的热力学性质,得到了温度对热力学性能影响的关系式.1的性能研究表明,1的m.p.92℃～94℃,爆速8 256m·s-1(1.85 g·cm-3),摩擦感度0％(90°摆角),撞击感度12％(10 kg,25 cm),特性落高H50 =57.5 cm(5 kg).     

Synthesis of Some 3‐Substituted Isochromen‐1‐ones

An alternative method for the synthesis of 3‐substituted isocoumarins from homophthalic acid and ester is described.     

Pyridazine Derivatives and Related Compounds,Part 17: 1 The Synthesis of Some 3-Substituted Pyridazino[3′, 4′:3, 4]pyrazolo[5, 1-c]-1,2,4-triazines and Their Antimicrobial Activity

The reaction of the hydrazide of pyridazino[3′, 4′:3, 4]pyrazolo[5, 1-c]-1,2,4-triazine-3-carboxylic acid 3 with carbon disulfide in the presence of potassium hydroxide gave the 1,3,4-oxadiazole-2-thione derivative 4. The methylation of this product in an alkaline medium proceeds at the sulfur atom. The reaction of 3 with KOH and carbon disulfide followed by addition of hydrazine hydrate afforded the 4-amino-1,2,4-triazole derivative 6. Compound 3, when heated either with ammonium thiocyanate or with potassium thiocyanate, afforded the same product 7, which underwent cyclodehydration in the presence of acetyl chloride, which led to the 2-acetylamino-1,3,4-thiadiazole derivative 8. In a basic medium, the product was 1,2,4-triazole-3-thione derivative 9. The reaction of 3 with phenyl isothiocyanate provided thiosemicarbazide derivative 10, which underwent cyclodehydration in a basic medium and gave the 1,2,4-triazole derivative 11. The reaction of 3 with formic acid yielded the 3-carboxyl-2′-(formyl)hydrazine derivative 12. The refluxing of the latter with phosphorus pentasulfide in xylene yielded compound 14 (65%). The reaction of compound 12 with phosphorus pentoxide afforded compound 15. Some representative examples were screened for antimicrobial activity.     

Novel Synthesis of 3‐Amino‐4‐oxo‐(2H)‐pyrazolo[3′,4′:4,5]pyrimido‐[2,1‐b]benzothiazole and its 2‐ and 3‐Substituted Derivatives

Reaction of 4H‐pyrimido[2,1‐b]benzothiazole‐2‐thiomethyl‐3‐cyano‐4‐one (1) with hydrazine hydrate/aryl hydrazine/heteryl hydrazine in the presence of anhydrous potassium carbonate and dimethyl formamide afforded 3‐amino‐4‐oxo‐(2H)/aryl/heteryl pyrazolo[3′,4′:4,5]pyrimido[2,1‐b]benzothiazoles in good yield. These pyrazole derivatives on diazotization followed by replacement with hydroxy, chloro, bromo, iodo and on reduction gave the corresponding 3‐substituted derivatives.     

Stereoselective Synthesis of [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐D‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐L‐valine]cyclosporin A

Addition of various amines to the 3,3‐bis(trifluoromethyl)acrylamides 10a and 10b gave the tripeptides 11a – 11f , mostly as mixtures of epimers (Scheme 3). The crystalline tripeptide 11f ₂ was found to be the N‐terminal (2‐hydroxyethoxy)‐substituted (R,S,S)‐ester HOCH₂CH₂O‐D ‐Val(F₆)‐MeLeu‐Ala‐O^tBu by X‐ray crystallography. The C‐terminal‐protected tripeptide 11f ₂ was condensed with the N‐terminus octapeptide 2b to the depsipeptide 12a which was thermally rearranged to the undecapeptide 13a (Scheme 4). The condensation of the epimeric tripeptide 11f ₁ with the octapeptide 2b gave the undecapeptide 13b directly. The undecapeptides 13a and 13b were fully deprotected and cyclized to the [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐D ‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐L ‐valine]]cyclosporins 14a and 14b , respectively (Scheme 5). Rate differences observed for the thermal rearrangements of 12a to 13a and of 12b to 13b are discussed.     

Stereochemistry of Formation of the β‐Ring of Lycopene: Biosynthesis of (1R,1′R)‐β,β‐[16,16,16,16′,16′,16′‐2H6]Carotene from [16,16,16,16′,16′,16′‐2H6]Lycopene in Flavobacterium R 1560

Incubation of deuteriated precursors in cultures of Flavobacterium produced specifically deuteriated carotenoids. Analysis of these led to several conclusions: i) Lycopene is a direct precursor of β,β‐carotene. ii) Its terminal Me groups retain their integrity during cyclization: there is a stereospecific folding of the 1,5‐diene. The Me(16,16′) groups of lycopene become the Me(16,16′) of β,β‐carotene. Consequently, the folding must follow the C₂(E,E) mode. iii) Incorporation of deuterium was sufficiently extensive to permit CD measurements on the isolated β,β‐carotene, allowing its centers of chirality to be assigned as (1S,1′S). iv) The same chirality resulted from incorporation of [²H₃]mevalonate into zeaxanthin. The syntheses of specifically deuteriated [²H₃]GPP, [²H₃]FPP, and [²H₃]GG are described.     

Synthesis of 3′,4′‐Diaryl‐4′H‐spiro[indoline‐3,5′‐[1′,2′,4′]oxadiazol]‐2‐ones via DMAP‐catalyzed Domino Reactions and Their Antibacterial Activity

A convenient and metal‐free DMAP‐catalyzed domino reaction of isatins, arylamines and hydroximoyl chlorides has been developed to achieve 1,3‐dipolar cycloaddition of imines into aryl nitrile oxides at ambient temperature. In this one‐pot transformation, a 1,2,4‐oxadiazole skeleton was efficiently formed. This methodology needs no extra additives and features wide substrate scope, good functional group tolerance and mild reaction conditions. A plausible mechanism for this process was proposed. Moreover, the antibacterial activities of the products were evaluated towards Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae using the Broth microdilution method.     

Synthesis,structure and some reactions of 4a',5′,6′,7′,8′,8a'‐hexahydro‐4′H‐spiro[cyclohexane‐1,9′‐[1,2,4]triazolo[5,1‐b]‐quinazolines]

2′‐Substituted 5′,6′,7′,8′‐tetrahydro‐4′H‐spiro[cyclohexane‐1,9′‐[1,2,4]triazolo[5,1‐b]quinazolines] 3a‐d were synthesized by condensation of 3‐substituted 5‐amino‐1,2,4‐triazoles 1a‐d with 2‐cyclohexylidene cyclohexanone 2 in DMF. The compounds 3 were hydrogenated with sodium borohydride in ethanol to give 2′‐substituted cis‐4a',5′,6′,7′,8′,8a'‐hexahydro‐4′H‐spiro[cyclohexane‐1,9′‐[1,2,4]triazolo[5,1‐b]quinazolines] 4a‐d in high yields. The reactions of alkylation, acylation and sulfonylation of the compounds 4 were studied. The structure of the synthesized compounds was determined on the basis of NMR measurements including HSQC, HMBC, NOESY techniques and confirmed by the X‐ray analysis of 6 and 11b . The described synthetic protocols provide rapid access to novel and diversely substituted hydrogenated [1,2,4]triazolo[5,1‐b]quinazolines.     

Carbon Magnetic Resonance Spectra of α, β, γ, δ- and α, β, α′, β′- Unsaturated Ketones

Carbon-13 spectra of a series of 26 unsaturated ketones (ortho- and para-cyclo-hexadienones and corresponding open-chain analogues) have been measured by Fourier-transform. Pulse spectroscopy. A complete analysis has been achieved by means of double resonance experiments using noise-modulated and coherent off-resonance proton irradiation and with the aid of non-decoupled spectra. Chemical shifts are interpreted in terms of charge distribution in the dienone system and of methyl substituent effects. Carbon chemical shifts were also obtained for O-protonated ortho- and para-cyclohexadienones. One-bond and long-range carbon-proton and carbon-fluorine spin coupling constants are reported for several compounds.     

Synthesis of novel α,α′,β-trisubstituted β-lactones

A concise and efficient synthesis of α,α′,β-trisubstituted β-lactones is presented. These novel lactones are easily obtained in five steps and will be dedicated to anionic ring opening polymerization.     

Synthesis of spiro[3,4‐diaryl‐4,5‐dihydroisoxazole‐5,2′‐1′,2′,3′,4‐tetrahydro‐1′‐naphthalenone]

Synthesis of a series of novel spiro[3,4‐diaryl‐4,5‐dihydroisoxazole‐5,2′‐1′,2′,3′,4′‐tetrahydro‐1′‐naphthalenone] has been described by the regioselective cycloaddition of nitrile oxides with 2‐arylmethylene‐1,2,3,4‐tetrahydro‐1‐naphthalenone. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:463–467, 2001