Syntheses and transformations of novel nitrogen and sulfur containing morphinanedienes

Summary The synthesis of 6-azido-6-demethoxythebaine (10) has been performed starting from thebaine (1). Compound10 undergoes a cycloaddition reaction with the azadienophilePTAD to form bridgehead azide14. The acid catalyzed rearrangement of isothiocyanato diene11 obtained from azido diene10 and thiocyanato dienes8 and9 leads to sulfur containing derivatives of apocodeine (17–20).

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Darstellung und Reaktionen stickstoff- und schwefelhaltiger Morphinandiene

Zusammenfassung 6-Azido-6-demethoxythebain (10) wurde ausgehend von Thebain (1) hergestellt. Verbindung10 wurde in einer Cycloadditionsreaktion mit dem AzadienophilPTAD zum Brückenkopfazid14 umgesetzt. Das aus dem Azidodien10 erhältliche Isothiocyanatodien11 und die bereits früher gewonnenen Thiocyanatodiene8 und9 liefern bei säurekatalysierter Umlagerung die Apokodeinderivate17–20.

     

Nukleophile Substitutionen und Eliminierungen von Aminofunktionen via Pyrimidiniumsalze

Reaction of 2,4-diphenyl-1,3-thiazine-6-thione (1) with primary amines leads under ring transformation to 1-organyl-pyrimidine-6-thiones3, which are alkylated to 1-organyl-6-methylthiopyrimidinium salts5. The latter allow a transfer of the 1-organyl group to nucleophilic agents by departure of 2,4-diphenyl-6-methylthio-pyrimidine (8). In special cases an elimination reaction is successful. Preparative advantages and limitations are demonstrated and discussed.

     

Metal ion-assisted assembly of one-dimensional polyrotaxanes incorporating cucurbit[6]uril

Three cucurbit[6]uril (CB[6])-based polyrotaxanes [Cu(H₂ C6N4)(CB[6])]Cl₄·12H₂O (1), [Co(H₂ C6N4)(CB[6])]Cl₄·14H₂O (2) and [Ag(C6N4)(CB[6])]NO₃·7H₂O (3) are prepared using N,N′-bis(4-pyridylmethyl)-1,6-hexanediamine (C6N4) threading into CB[6]'s and metal ions' assistance. Single-crystal X-ray diffraction analyses reveal that polyrotaxanes 1, 2 and 3 all have 1D chain structure where 1 and 2 are linear and 3 has two shapes, linear and sawtooth, respectively. The effects of guest molecules, metal and counter ions as well as intermolecular weak interactions on the architectures of polyrotaxanes are discussed.     

Studies on Pyrazine Derivatives,XLIII: Synthesis and Antituberculosis Activity of 6-(1,2,3,4-Tetrahydroisoquinolino) and 6-(1,3,3-Trimethyl-6-azabicyclo-[3, 2, 1]-octano)-pyrazinocarboxylic Acid Derivatives

The reactivity of the chloride atom of 2-cyano-6-chloropyrazine was used in the reactions with amines, 1,2,3,4-tetrahydroisoquinoline and 1,3,3-trimethyl-6-azabicyclo-[3,2,1]-octane, which yielded the substrates for the syntheses of a series of new derivatives. The bulk of them were tested for their tuberculostatic activity. MIC values of the most active ones ( 2a , b , 5b , 7a , 9b , and 11b ) were within 3.1–50 μ g/mL.     

Synthesis of 20-hydroxyecdysone 6-chloronicotinates

New esters 2-5 that contain 6-chloropyridine groups characteristic of the alkaloid epibatidine were prepared by acylation of 20-hydroxyecdysone (1) by 6-chloronicotinoylchloride. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 328–331, May–June, 2009.     

1,3-二(乙氧基甲基)-5-N,N-二甲氨基-6-甲基尿嘧啶的合成

报道了1,3-二(乙氧基甲基)-5-N,N-二甲氨基-6-甲基尿嘧啶方便、高产率的合成方法. 以6-甲基尿嘧啶(1)为起始物, 经硝化、嘧啶N¹,N ³-烷基化、还原及氨基甲基化, 首次高产率合成了1,3-二(乙氧基甲基)-5- N,N -二甲氨基-6-甲基尿嘧啶(5), 并对其化学结构进行了表征.     

含卤素端基的单取代对-叔丁基杯[6]芳烃的合成与表征

用THF作为反应溶剂, K₂CO₃作碱, 对-叔丁基杯[6]芳烃与二溴丁烷、二溴己烷和1,4-二氯丁炔-2反应以中等产率选择性地合成了含有卤素端基的单取代对-叔丁基杯[6]芳烃2a～2c. 2a和2b可与对甲苯磺酸甲酯(MeOTs)反应高产率地得到全甲基化产物3a和3b. 通过核磁共振谱(¹H NMR)和质谱(FAB-MS)表征, 发现所有化合物都具有预期结构, 2a～2c和3b在室温下是锥式构象, 而3a没有固定构象.     

Concise Synthesis of 6-Cyanobenzo[b]furan,a Useful Building Block

A new three-step synthesis of 6-cyanobenzo[b]furan (6) was developed, starting from commercially available 6-hydroxybenzo[b]furan-3-one (18). Key steps in this process were the first step, which was the reductive dehydration of 18 to produce 6-hydroxybenzo[b]furan (19), and the last step, which converted the aryl triflate 20 to the aryl cyanide 6 in a palladium-catalyzed cross-coupling protocol. Overall yield for this new synthesis was 49%.     

New lanthanide-based complexes constructed from cucurbit[6]uril: Synthesis,structures and properties

Three lanthanide-based complexes, {Gd₂(H₂O)₁₀(CB[6])₂}·CB[6]·6Cl·12H₂O (1), {[Gd₂(H₂O)₈CB[6]₂]·(CuCl₄)·4Cl·46H₂O}_n (2), and {Dy₂(NO₃)₂(H₂O)₁₀(CB[6])}·4NO₃·14H₂O (3) (CB[6] = cucurbit[6]uril), were prepared with cucurbit[6]uril (CB[6]). These complexes were characterized by single-crystal X-ray diffraction, elemental analysis, FT-IR spectroscopy, UV–Vis spectroscopy, thermogravimetric analysis and magnetization measurements. Crystallographic results showed that 1 and 3 are dinuclear and crystallize in the triclinic space group Pī, whereas 2 is a 1-D zigzag supramolecular chain that crystallizes in the monoclinic system in C2/c. The results indicated that temperature has a big effect on the supramolecular assemblies and a different structure inducer also leads to the formation of different coordination polymers. Frequency dependence in the ac susceptibility signals was observed in 3.     

利用工业废弃物中获得的(R)-5-甲基-δ-戊酸内酯为原料合成(2R,6R)-2,6,10-三甲基十一醇

(2R,6R)-2,6,10-三甲基十一醇(1)是维生素E、维生素K和植醇的基本结构单元. 利用从甾体皂甙元氧化降解产生的工业废弃物中所获得的手性化合物(R)-5-甲基-δ-戊酸内酯(6), 先将其转化成为化学性质稳定的(4R)-甲基-5-甲氧甲氧基戊酸甲酯(7), 再经十二步反应, 以14.1%的总收率合成得到了目标化合物(2R,6R)-2,6,10-三甲基十一醇(1).     

Synthesis of 6α-methyl-16α,17α-cyclohexano-19-norprogesterone from a 19-methyl-6-desmethyl precursor

After prolonged refluxing of 19-tosyloxy-16α,17α-cyclohexanopregn-5-en-3β-ol-20-one (3) with NaI in 2-propanol, the initially formed 19-iodo derivative (4) undergoes supraface migration of the CH₂I group from the C(10) atom to the C(6) atom, probably through involvement of a homoallyl cation. The resulting 6β-iodomethyl-16α,17α-cyclohexano-19-norpregn-5(10)-en-3β-ol (5) was transformed in three steps into 6α-methyl-16α,17α-cyclohexano-19-norprogesterone (6α-methyl-19-nor-D′ ₆-pentarane,8). The transformation of compound5 into the target product8 also gave a side product, a pentarane with aromatic ringA (10), which was isolated and characterized by spectroscopic methods. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1688–1691, September, 1997.     

Total synthesis of an isoflavone C-glycoside: 6-tert-butylpuerarin

The first total synthesis of an isoflavone C-glycoside (6-tert-butylpuerarin) using commercially available 4,6-di-tert-butylbenzene-1,3-diol as starting material was achieved in five steps with an overall yield of 2.8%. The key intermediate 4 was obtained by de-tert-butylation of 2 with trifluoroacetic acid and Friedel-Crafts acetylation of 2-C-β-D-glucopyranoside 3. Condensation of 4 with 4-(benzyloxy)benzaldehyde resulted in the formation of C-glucosylchalcone 5, which was cyclized by oxidative rearrangement using (diacetoxyiodo)benzene (DIB) and p-toluenesulfonic acid to obtain the target molecule 6. This environmentally friendly and concise synthetic pathway should be applicable to the large-scale synthesis of various isoflavone C-glycosides.     

Angucycline antibiotics and its derivatives from marine-derived actinomycete Streptomyces sp. A6H

Vineomycin A₁ (1) and B₂ (2) were isolated from the culture broth of marine actinomycete Streptomyces sp. A6H. Five hydrolysis products were obtained by rational hydrolysis and methanolysis of the fermentation extract. Their structures were characterised as aquayamycin (3), vineomycinone B₂ (4), 9-C-_D-olivosyltetrangulol (5), 7-O-methylgaltamycinone (6) and vineomycinone B₂ methyl ester (7). In addition to these compounds, two ester derivatives, vineolactone A (8) and vineomycinone B₂ benzyl ester (9) of compound 4 were generated semisynthetically. Compound 6 is a new analogue of galtamycinone, while compounds 8 and 9 are new members of vineomycins. Cytotoxic activities and antimicrobial activities were determined for all compounds. The results indicate that only compound 1 showed significant activities with IC₅₀ value of 0.34 μM against H1975 and MIC value of 4 μg/mL against Staphylococcus aureus.     

Addition compounds of nucleophiles and 3-ethylthio-6-oxo-6H-1,2-dithiolo[4,3-c]1,2-dithiolium tetrafluoroborate. Synthesis of 3H,6H-1,2-dithiolo[4,3-c]1,2-dithiole-3-one-6-thione

Summary A smooth method of synthesizing 3H, 6H-1,2-dithiolo[4,3-c]1,2-dithiole-3,6-dithione (3), and also its partial desulfuration to yield 3H, 6H-1,2-dithiolo[4,3-c]1,2-dithiole-3-one-6-thione (4) is presented. The ethylation product5 of the monothione4 reacts with various nucleophilic reagents to form remarkably stable adducts. The adducts of5 with methanol,tert-butyl mercaptan, and with aniline could be isolated and characterized by their¹H-NMR spectra.

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Anlagerungsverbindungen von Nukleophilen an 3-Ethylthio-6-oxo-6H-1,2-dithiolo[4,3-c]1,2-dithioliumtetrafluoroborat. Synthese von 3H,6H-1,2-Dithiolo[4,3-c]1,2-dithiol-3-on-6-thion

Zusammenfassung Eine glatte Synthese für 3H,6H-1,2-Dithiolo[4,3-c]1,2-dithiol-3,6-dithion (3) und für dessen partielle Entschwefelung zu 3H,6H-1,2-Dithiolo[4,3-c]1,2-dithiol-3-on-6-thion (4) wird angegeben. Das Ethylierungsprodukt5 des Monothions4 reagiert mit unterschiedlichen Nukleophilen zu bemerkenswert stabilen Addukten. Die Addukte mit Methanol,tert.-Butylmercaptan und mit Anilin wurden isoliert und durch ihr¹H-NMR-Spektrum charakterisiert.

     

Microwave-Promoted Syntheses of Pyridine Carboxamides and tert-Carboximides from Novel 6-Acetylpyridine-2-carboxylic Acid

A novel 6-acetylpyridine-2-carboxylic acid (4) was obtained occasionally during the synthesis of asymmetric ethyl 6-acetylpyridine-2-carboxylate (3) from 2,6-dipiclinic acid (1). Compounds 3 and 4 could transform mutually under some specific conditions. Two reactions of distinctive types occurred when they reacted with the aromatic amines as precursors, due to different functional groups on the 2-position of pyridine in the molecules of 3 and 4: one was Schiff base condensation and the other was an amidation reaction. From the latter reaction, two series of new compounds, pyridine carboxamides (5a–d) and pyridine tert-carboximides (6a–h), resulted. The relevant reaction mechanism is discussed in detail.     

Synthesis and anticancer activity of some novel benzothiazole-thiazolidine derivatives

Sixteen new 2-(benzothiazol-2-ylthio)-N′-(3-substituted-4-(3,4-substitutedphenyl)thiazol-2(3H)-ylidene)acetohydrazide derivatives (4a-4p) were synthesized. The structures of the synthesized compounds were elucidated using FT-IR, ¹H-NMR, ¹³C-NMR, and HRMS spectral data. Anticancer activity of the compounds 4a-4p against C6 (rat brain glioma) and A549 (human lung adenocarcinoma) cell lines was evaluated by using MTT, inhibition of DNA synthesis, and flow cytometric analysis assays. According to MTT assay, 4a and 4d were found to be the most active compounds against C6 cell line with an IC₅₀ value of 0.03 mM. Moreover, IC₅₀ values of 4a (0.2 mM) and 4d (0.1 mM) against NIH3T3 (mouse embryo fibroblast cell line) were higher than their IC₅₀ values (0.03 mM) against C6 cell line. Accordingly, selectivity of compound 4a against C6 cell line was two-fold higher than that of compound 4d. Flow cytometry analysis showed that these compounds display anticancer activity by inducing apoptosis. As a result, compound 4a has a remarkable anticancer activity and a good selectivity towards C6 cell lines.     

Kinetic and thermodynamic inclusion complexes of symmetric teramethyl-substituted cucurbit[6]uril with HCl salts of N,N′-bis(pyridylmethyl)-1,6-hexanediamine

The host–guest interaction of symmetrical α,α′,δ,δ′-tetramethyl-cucurbit[6]uril (TMeQ[6]) with the hydrochloride salts of N,N′-bis(4-pyridylmethyl)-1,6-hexanediamine (P6), N,N′-bis(3-pyridyl-methyl)-1,6-hexanediamine (M6) and N,N′-bis(2-pyridylmethyl)-1,6-hexanediamine (O6) was investigated via single crystal X-ray diffraction, ¹H NMR spectroscopy, electronic absorption spectroscopy and fluorescence spectroscopy. Single crystal X-ray diffraction showed that the hexyl moiety of P6 or M6 was incorporated in the cavity of TMeQ[6], while the two pyridylmethyl moieties of O6 were incorporated in the TMeQ[6] cavity in the solid state. The ¹H NMR results in aqueous solution revealed that the TMeQ[6]-P6 and TMeQ[6]-M6 host–guest interaction systems produce a kinetic dumbbell-shaped inclusion complex at the initial stage and then an equilibrium pseudorotaxane-shaped inclusion complex as the only product after heating. However, only the pseudorotaxane-shaped inclusion complex was observed for the TMeQ[6]-O6 host–guest interaction system. Aqueous absorption spectrophotometric analysis showed that the dumbbell-shaped inclusion complexes were stable at pH 5.6, had a host–guest ratio of 2:1 and formed quantitatively at ～10¹¹ l²/mol² for the TMeQ[6]-M6 and TMeQ[6]-O6 systems. The transformation from dumbbell to pseudorotaxane-shaped inclusion complexes for the TMeQ[6]-P6 and TMeQ[6]-M6 host–guest systems yielded activation energies of 59.35 ± 1.55 and 78.7 ± 3.45 kJ/mol, respectively. The pseudorotaxane-shaped inclusion complexes were stable at pH 5.6, had a host–guest ratio of 1:1 and formed quantitatively at ～10⁷ l/mol for the TMeQ[6]-M6 and TMeQ[6]-P6 systems.     

A Determination of 6-Mercaptopurine and 6-Thio-Guanine By Anodic Differential Pulse Voltammetry

Abstract

The anodic oxidation of 6-mercaptopurine and 6-thioguanine has been studied on a rotating and stationary disk electrode of glassy carbon, using d.c. and differential pulse potential program. Conditions have been found for determination of these substances by anodic differential pulse voltammetry on a rotating disk electrode, with a detection limit of about 2 × 10^?5 mol 1^?1.     

Convenient synthesis of linear 2H,6H-pyrano[3,2-g] chromenes from natural occurring compound; visnagin

Abstract

A simple and convenient rout for the synthesis of linear 2-imino-2H,6H-pyrano[3,2-g] chromen-6-ones and 2H,6H-pyrano[3,2-g]chromene-2,6-diones has been described starting from natural occurring furochromone; visnagin (1). Ring opening of 1 yielded 6-formyl-7-hydroxy-5-methoxy-2-methylchromone (2), which underwent reaction with different acetonitrile derivatives furnished 2-imino-2H,6H-pyrano[3,2-g] chromen-6-ones (5a–h). Acid hydrolysis of 5a–h led to the formation of 2H,6H-pyrano[3,2-g]chromene-2,6-diones (6a–h). Structures of the synthesized compounds were clarified based on their elemental analyses and spectral data. The entire target compounds were selected for in vitro anticancer activity against 60 human cancer cell lines at a single dose (10^?5 M) by the National Cancer Institute (NCI, Bethesda, USA).     

Crystal structures of inclusion compounds of 4-aminobenzenesulfamidine (sulfaguanidine) with two dicyclohexano-18-crown-6 isomers

The crystal structures of inclusion compounds of 4-aminobenzenesulfamidine (sulfaguanidine) (L) with two dicyclohexano-18-crown-6 (DCH-6) isomers A(cis-syn-cis) and B(cis-anti-cis) have been determined by X-ray methods. The complexes exhibit 1:2 host-guest ratios. In fact the complex of isomer A is formulated as [DCH-6^A·[L]H₂O]L (complexI), while that of isomerB is DCH-6 ^B L₂ (complex I1).In the crystals, host and guests are connected by O-H...0 and N-H...O bonds.