新型环烷烯并嘧啶并噻唑-3-酮类化合物的合成

以环戊酮、环庚酮为起始原料合成的环烷烯并[1,2-d]嘧啶-2-硫酮(2)与氯乙酸、芳香醛反应, 合成具有潜在抗癌活性的稠合杂环化合物5-芳基-2,8-二芳亚甲基-2,3,6,7-四氢-5H,8H-环戊烯并[1,2-d]噻唑并[3,2-a]嘧啶-3-酮(3)以及5-芳基-2,10-二芳亚甲基-2,3,6,7,8,9-六氢-5H,10H-环庚烯并[1,2-d]噻唑并[3,2-a]嘧啶-3-酮(4). 3和4的结构经¹H NMR, IR, MS分析确认.     

溴代芳香碳糖苷的高效合成方法

首先在三氟乙酸银和无水四氯化锡体系中合成芳香碳糖苷2-(2,3,4,6-四-O-乙酰基-β-D-吡喃糖)-1,4-二甲氧基苯(4a和4b), 再以弱路易斯酸硝酸铵为催化剂, 使用N-溴代丁二酰亚胺(NBS)在温和条件下溴化4a和4b, 高产率地得到2-(2,3,4,6-四-O-乙酰基-β-D-吡喃糖)-5-溴-1,4-二甲氧基苯(1a和1b); 讨论了NBS和硝酸铵的用量对溴化反应的影响, 并对产物的NMR进行了解析.     

N-烷基/芳基-N'-(4-芳基噻唑-2-基)-N"-糖基胍的合成及生物活性研究

2,3,4,6-四-O-乙酰基-β-D-吡喃葡萄糖基异硫氰酸酯(1)与2-氨基-4-取代苯基噻唑(2a～2b)反应, 生成糖基硫脲衍生物3a～3b, 再在伯胺存在下经氯化汞脱硫, 得到一系列新的N-烷基/芳基-N'-(4-芳基噻唑-2-基)-N"-糖基胍类化合物(4a～4e, 5a～5e). 所有新化合物的结构均经IR, ¹H NMR, MS谱和元素分析证实, 所得产物均为β-构型. 生物活性测试结果表明, 化合物4b和5d对HIV-1 PR表现出了较高的抑制活性.     

新型1,2,4-三唑[3,4-b]-1,3,4-噻二嗪的合成及表征

以3-(2-苯基-1,2,3-三唑-4-基)-4-氨基-5-巯基-1,2,4-三唑(1)为原料分别与ω-溴代芳基乙酮、ω-溴代-ω-(1H-1,2,4-三 唑-1-基)芳基乙酮反应, 合成了一系列新的1,2,4-三唑[3,4-b]-1,3,4-噻二嗪类化合物2a～2e和3a～3e. 其结构经IR, ¹H NMR和MS及元素分析确证.     

含三唑基的新型咪唑[2,1-b]-1,3,4-噻二唑的合成及表征

以2-(2-苯基-1,2,3-三唑-4-基)-5-氨基-1,3,4-噻二唑(1)为原料分别与ω-溴代芳基乙酮、ω-溴代-ω-(1H-1,2,4-三唑-1-基)芳基乙酮反应, 合成了一系列新型咪唑[2,1-b]-1,3,4-噻二唑类化合物2a～2e和3a～3e. 其结构经IR, ¹H NMR和MS及元素分析确证.     

新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物的合成及抗菌活性

通过3-取代-4-氨基-5-巯基-1,2,4-三唑(3a～3m)和2-溴-2-(1H–1,2,4-三唑-1-基)-4′-氯代苯乙酮(2)的缩合反应, 合成了13个新型3-取代-6-(4-氯苯基)-7-(1H-1,2,4-三唑-1-基)-1',2',4'-三唑[3,4-b]-1",3",4"-噻二嗪衍生物4a～4m. 化合物结构经元素分析, ¹H NMR, IR和MS进行了表征. 抗菌试验表明所合成的化合物对细菌表现出中等程度的抑制活性.     

微波辐射下2-氨基-7-甲基-4-芳基-5-氧代-4H,5H-吡喃并[4,3-b]吡喃-3-腈的一步合成

芳醛、丙二腈与6-甲基-4-羟基-2-吡喃酮在微波辐射下, 一步反应得到一系列2-氨基-7-甲基-4-芳基-5-氧代-4H,5H-吡喃并[4,3-b]吡喃-3-腈, 该反应时间短、产率较高、环境友好、后处理简单. 产物的结构经红外光谱、核磁共振谱和元素分析表征, 产物4g的结构经单晶X射线衍射进一步确证; 并对反应过程提出了可能的机理.     

含苯并噻唑基乳糖基胍的合成

2,3,6,2',3',4',6'-七-O-乙酰基-β-乳糖基异硫氰酸酯(1)分别与2-氨基-4/6-取代苯并噻唑2a～2e反应, 制得糖基硫脲3a～3e, 将其在HgCl₂作用下与伯胺反应, 制得一系列新化合物N-烷基/芳基-N'-(4/6-取代-苯并噻唑-2-基)-N'-(2,3,6,2',3',4',6'-七-O-乙酰基-β-乳糖基)胍4～6. 然后, 在CH₃ONa/CH₃OH作用下, 脱乙酰基得含苯并噻唑基的乳糖基胍类化合物7～9. 所有新化合物的结构均经IR, ¹H NMR, MS谱和元素分析证实, 所得产物均为b-构型. 对代表性化合物的生物活性测试结果表明, 乳糖基胍类化合物对HIV-1蛋白酶、血管紧张素转化酶(ACE)的抑制活性较差.     

黑龙骨中两个新强心苷的结构鉴定

系统研究黑龙骨Periploca forrestii Schltr.中的化学成分, 利用各种色谱技术进行分离, 得到2个新类型的强心苷,黑龙骨苷甲和乙. 并通过化学和光谱方法(MS, ¹H, ¹³C NMR和2D NMR)鉴定其结构为: 5β-羟基-8,14β-环氧-强心 甾- 20(22)-烯-3-O-β-D-磁麻吡喃糖苷(1)和5β-羟基-8,14β-环氧-强心甾-20(22)-烯-3-O-β-D-葡萄吡喃糖基-(1→4)-β-D-磁麻吡喃糖苷(2).     

基于2-(4-吡啶基)-1H-咪唑-4,5-二羧酸配体的镉(Ⅱ)配合物的晶体结构及发光性质

在水热条件下,以2-(4-吡啶基)-1H-咪唑-4,5-二羧酸(H₃PIDC)和1,10-菲咯啉衍生物为混合配体合成了2个镉(Ⅱ)配合物{[Cd₃(HPIDC)₃(DPPZ)₃]·7H₂O}_n(1)和[Cd(HPIDC)(Imphen)(H₂O)]₂(2)(DPPZ=二吡啶并[3,2-a:2',3'-c]吩嗪;Imphen=咪唑并[4,5-f][1,10]菲咯啉),利用元素分析、红外光谱以及单晶X-射线衍射表征其结构。分析表明配合物1和2分别为一维链状与零维结构。此外,2个配合物展示了优良的热稳定性及光致发光特性。     

Stable simple enols. Self-catalyzed E/Z-isomerization of the sterically crowded 2-(m-methoxymesityl)-1,2-dimesitylethenol

(E)-2-(m-methoxymesityl)-1,2-dimesitylethenol (3a) isomerizes in the absence of a catalyst in solution to a 1.0:0.9 E/Z (3a/3b) equilibrium mixture. In CDCl3 the isomerization is first order in 3a within a run, but the plot of the rate constant k(obs) vs the changing [3a]0 in different runs is a half-parabola, indicating self-catalysis by more than one enol molecule. At 0.09 M enol, the isotope effect k(3a)/k(3a)-OD = 2.1. In the presence of 0.025-0.25 M pyridine-d5, the k(obs) vs [pyridine-d5] plot displays a bell-shaped profile. The change in the shape of the OH signals of the 3a/3b mixture at 295-430 K in C6D5NO2 was followed by DNMR. The four signals of the diastereomeric 3a/3b mixture observed at 330 K coalesce at 350 K with barriers of 18.3 and 18.4 kcal x mol(-1) due to the diastereomerization of the vinyl propellers. The resulting two signals observed at >360 K further coalesce at 425 K with a barrier of 22.9 kcal x mol(-1) due either to oxygen-to-oxygen proton exchange or to E/Z isomerization. The estimated upper limit for the rate of proton exchange of k(ex) < or = (2-4) x 10(3) M(-1) x s(-1) at 425 K between the enol molecules is sufficiently slow to be a rate-controlling step in the isomerization. A process in which several enol molecules catalyze the isomerization is suggested, and several mechanistic routes are analyzed.     

Synthesis of the hydroazulene portion of guanacastepene A using a [2.3]sigmatropic sulfoxide rearrangement: observations on silyl enol ether electrophilic chemistry for the introduction of the C-13 hydroxyl group

The intermediate 6 can be converted into enone 13 using a [2.3]sigmatropic sulfoxide rearrangement as the key transformation. The C-13 hydroxylation of 13 was studied, and found to give 14 (epimeric to guanacastepene A). Examination of silyl enol ethers of 13 demonstrated the ready isomerization of the kinetic silyl enol ether into the more stable thermodynamic silyl enol ether under mild electrophilic reaction conditions.     

Regio- and stereodefined synthesis of trimethylsilyl enol ethers resulted from the isomerization of α-trimethylsilyl ketones

The isomerization of an α-trimethylsilyl ketone is lead to the corresponding trimethylsilyl enol ether with the enhanced regioselectivity by heating or by the assist of trimethylsilyl trifluoromethanesulfonate. The thermal reaction discloses a new regiodefined (E)-selective route to silyl enol ethers.     

New approaches toward the synthesis of (D-homo) steroid skeletons using Mukaiyama reactions

New, short, and flexible procedures have been developed for syntheses of steroid and D-homo steroid skeletons. A Mukaiyama reaction between the silyl enol ether of 6-methoxytetralone and 2-methyl-2-cyclopentenone or carvone, with transfer of the silyl group to the receiving enone, gave a second silyl enol ether. Addition of a carbocation, generated under Lewis acid conditions from 3-methoxy-2-butenol, 3-ethoxy-3-phenyl-2-propenol or 3-methoxy-2-propenol to this second silyl enol ether gave adducts, which could not be cyclized by aldol condensation to (D-homo) steroid skeletons. The Mukaiyama-Michael reaction of the silyl enol ether of 6-methoxy tetralone with 2-methyl-2-cylopentenone gave a second silyl enol ether, which reacted in high yield with a carbocation generated from 3-hydroxy-3-(4-methoxyphenyl)propene. Ozonolysis of the double bond in this adduct gave a tricarbonyl compound (Zieglers triketone), which has been used before in the synthesis of 9,11-dehydroestrone methyl ether. A second synthesis of C17 substituted CD-trans coupled (D-homo) steroid skeletons has been developed via addition of a carbocation, generated with ZnBr₂ from a Torgov reagent, to a silyl enol ether containing ring D precursor. The obtained seco steroids have been cyclized under formation of the 8-14 bond by treatment with acid. The double bonds in one of the cyclized products have been reduced to a C17-substituted all trans steroid skeleton.     

Cyclooctanone synthesis via a formal [6+2] cycloaddition reaction of a dicobalt acetylene complex

An efficient formal [6+2] cycloaddition reaction of a new six-carbon unit with enol silyl ether was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAlCl₂, 6-benzoyloxy-2-(triisopropylsilyloxy)-1-hexen-4-yne-dicobalthexacarbonyl reacted with enol triisopropylsilyl ethers to yield 7-(triisopropylsilyloxy)-3-cyclooctyn-1-one-dicobalthexacarbonyl derivatives in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity.     

Discovery of a phosphine-mediated cycloisomerization of alkynyl hemiketals: access to spiroketals and dihydropyrazoles via tandem reactions

Reported here are details on the discovery of a phosphine-catalyzed isomerization of hemiketals and subsequent reactions of the cyclic keto enol ether products. The new cycloisomerization complements a previously reported amine-catalyzed process that gave oxepinones from the same hemiketal starting materials. In the absence of functionality (R(2)) on the cyclic keto enol ether, a rapid and facile dimerization occurs, giving spiroketal products. When the enone is substituted (i.e., R(2) = Ph), the cyclic keto enol ether is sufficiently stable so that it can be isolated; it can then be further reacted in the same pot to provide the corresponding dihydropyrazoles. Both the spiroketal and dihydropyrazole products arise by a tandem reaction that begins with the novel cycloisomerization. The method allows for the rapid introduction of complexity in the products from relatively simple starting materials. It should find application in the synthesis of natural product-like molecules.     

The Ireland-Claisen rearrangement as a probe for the diastereoselectivity of nucleophilic attack on a double bond adjacent to a stereogenic centre carrying a silyl group

The E- and Z-silyl enol ethers 4 derived from allyl 3-R-3-dimethyl(phenyl)silylpropanoate (R = Me, Pr(i) and Ph) and the Z-silyl enol ethers 7 derived from 4-R-4-dimethyl(phenyl)silylbut-2-enyl acetate (R = Me and Pr(i)) undergo Ireland-Claisen rearrangements largely in the same stereochemical sense, with C-C bond formation taking place anti to the silyl group in the conformations 22, 23 and 24 in which the hydrogen atom on the stereogenic centre is inside, more or less eclipsing the double bond. The E-silyl enol ether E-7a derived from 4-methyl-4-dimethyl(phenyl)silylbut-2-enyl acetate shows low diastereoselectivity in the alternative sense, probably because C-C bond formation takes place anti to the silyl group in the conformation 26 with the methyl group inside, but the silyl enol ether E-7b derived from 4-isopropyl-4-dimethyl(phenyl)silylbut-2-enyl acetate shows low diastereoselectivity in the normal sense. The E- and Z-silyl enol ethers 33 derived from cis-crotyl 3-phenyl-3-dimethyl(phenyl)silylpropanoate and the E-silyl enol ether 39 derived from trans-crotyl 3-phenyl-3-dimethyl(phenyl)silylpropanoate undergo Ireland-Claisen rearrangements largely in the same stereochemical sense as their allyl counterparts, but with moderately high levels of diastereocontrol in setting up the third stereogenic centre following from chair-like transition structures.     

Ringerweiterung bei der Reaktion eines 1,3-Cyclohexandions mit Diphenylcyclopropenon

Ring Expansion during the Reaction of a 1,3-Cyclohexanedione with Diphenylcyclopropenone The reaction of 5,5-dimethyl-1,3-cyclohexanedione ( 1 ) in form of its Na-salt with diphenylcyclopropenone ( 2 ) in DMF yielded the bicyclic triketone 3 (58 %), the structure of which was deduced as an enolizeable bicyclo[5.2.0]nonane-β-diketone from spectral data and from the following reactions: hydrolysis or methanolysis of 3 cleaved the β-dicarbonyl moiety, thereby opening the 4-membered ring to yield the keto acid 9 or its methyl ester 10 . Methylation of 3 afforded the two enol ethers 4 and 5 . The ether 5 readily underwent a thermal electrocyclic ring opening to the monocyclic enol ether 8 , whereas the ether 4 was thermally stable. The same electrocylic ring opening (in boiling benzene) converted 3 (probably via 3b ) to the monocyclic triketone 7 , which was also the hydrolysis product of the ring-opened enol ether 8 . By heating 3 in DMF/H₂O, a partial (56 %) conversion to the lactone 6 took place. The tricyclic intermediate 11 was found useful to rationalize the ring expansion during the formation of 3 from 1 and 2 as well as the corresponding ring contraction during the conversion of 3 into 6 .     

Theoretical study on the mechanism of iron carbonyls mediated isomerization of allylic alcohols to saturated carbonyls

The conversion of allylic alcohols to enols mediated by Fe(CO)(3) has been studied through density functional theoretical calculations. From the results obtained a complete catalytic cycle has been proposed in which the first intermediate is the [(allyl alcohol)Fe(CO)(3)] complex. This intermediate evolves to the [(enol)Fe(CO)(3)] complex through two consecutive 1,3-hydrogen shifts involving a pi-allyl hydride intermediate. The highest Gibbs energy transition state corresponds to the partial decoordination ot the enol ligand prior to the coordination of a new allyl alcohol molecule that regenerates the first intermediate. Alternative processes for the [(enol)Fe(CO)(3)] complex such as [Fe(CO)(3)]-mediated enol-aldehyde transformation and enol isomerization have also been considered. The results obtained show that the former process is unfavourable, whereas the enol isomerization may compete with the enol decoordination step of the catalytic cycle.     

Regioselective transformation of alkynes into cyclic acetals and thioacetals with a gold(I) catalyst: comparison with Brønsted acid catalysts

Au(I) catalyzes the transformation of alkynes into cyclic acetals and thioacetals at much higher rate than Brønsted acids. The reaction appears to be general for a range of alkynes and diols or dithiols, which are efficiently transformed with high selectivities. One of the salient features of this reaction process is the high reactivity of the enol ether or enol thioether intermediates, which undergo a rapid isomerization reaction to afford the cyclic acetals or thioacetals, so that isolation or subsequent activation processes are not required. This type of reactions allows us to synthesize a series of fragrances.