二十四种作为麝香酮及类似大环酮重要中间体的长链二酮的仿生合成

烷基取代的大环酮（例如,名贵香料麝香酮）是珍贵的香料,天然来源稀少,它的人工合成一直是有机合成中的一个研究热点和难点。在本文中,受四氢叶酸辅酶的一碳单元转移反应的启发,作者以双苯并咪唑盐作为四氢叶酸辅酶模型,利用格利雅试剂与双苯并咪唑盐的加成-水解反应,成功合成了二十四种作为麝香酮及类似大环酮重要前体的长链二酮,同时,提供了一种麝香酮及类似大环酮的仿生合成新方法。     

Synthesis of 2,15-Hexadecanedione as a Precursor of Muscone

Muscone is a precious fragrant compound scarce in nature. Many synthetic attempts for this unique natural product have been carried out. In this work, the one-carbon unit transfer reaction of tetrahydrofolate coenzyme was initialed. Bisbenzimidazolium salt was used as tetrahydrofolate coenzyme model, and thus the biomimetic synthesis of 2,15-hexadecanedione, a precursor of muscone, was successfully accomplished by using the addition-hydrolysis reaction of bisbenzimidazolium salt with methyl magnesium iodide.     

Utility of Ketonic Mannich Bases in Synthesis of Some New Functionalized 2‐Pyrazolines

The styryl ketonic Mannich base 2 has been used as a precursor in the synthesis of 2‐pyrazolines having a basic side chain at C‐3 and a phenolic Mannich base at C‐5. Treatment of the bis(styryl ketonic bases) 6a and 8a with phenylhydrazine affords the bis(3‐functionalized 2‐pyrazolines) 7 and 9 . The transamination between the styryl keto base 10 and 4‐aminoantipyrine leads to 12 , which reacts with piperazine to give 13 . N‐Nitrosation of the sec‐Mannich bases 15a – d followed by reductive cyclization affords 2‐pyrazolines 17a – d . The keto base 14b has been used for the synthesis of 2‐pyrazolines having a phenolic Mannich base at C‐3 and its reaction with 3,5‐dimethyl‐1H‐pyrazole affords 23 . The alkylation of 3‐methyl‐1‐phenyl‐2‐pyrazolin‐5‐one with the bis(Mannich base) 25 was investigated.     

Novel Synthetic Method for Muscone

Muscone is a precious fragrant compound scarce in nature. Many attempts to synthesize this unique natural product have been carried out. In this work, a novel synthetic method for the preparation of muscone from 3‐methyl‐15‐hydroxypentadecanoate is provided. Benzimidazolium salt was used as tetrahydrofolate coenzyme model at formic acid oxidation level and Grignard reagent as nucleophile to which a one‐carbon unit was transferred. The biomimetic synthesis of muscone was successfully accomplished using the addition‐hydrolysis reaction of benzimidazolium salt with the Grignard reagent.     

Synthesis of novel Mannich bases and hybrid Mannich bases related to isoindolin-1,3-dione

Treatment of isoindolin-1,3-dione ( 1 ) with formalin and the appropriate amine or diamine afforded new N-Mannich bases and bis-(Mannich bases) 2 to 6 . The use of the appropriate hydrazide or dihydrazide as the amine component in the Mannich reaction with 1 led to Mannich bases and bis-(Mannich bases) incorporating a hydrazide moiety. The synthetic potential of sec-Mannich bases as precursors in synthesis of hybrid Mannich bases incorporating 1 was described. The N-alkylation of 1 with ketonic Mannich bases was investigated.     

Synthesis of a New Series of N‐Mannich Bases and Polyhydroxy Mannich Bases of Pharmaceutical Interest Related to Isatin and Its Schiff Bases

The reaction of isatin 1 with benzaldehyde and a sec‐amine or the appropriate aldimine afforded the N‐Mannich bases 2 – 3 and the bis‐base 4 . Treatment of 1 with glutaric dialdehyde and morpholine gave the bis‐base 5 . Mannich reaction of the Schiff bases 6a – f derived from 1 , led to the new Mannich bases and bis‐bases 7 – 9 . The use of N‐methyl‐D‐glucamine as the amine component in the Mannich reaction with 6b – f led to the polyhydroxy Mannich bases 11 – 13 .     

环己基甲酮类化合物的仿生合成新方法

以2位环己基取代苯并咪唑盐作为甲酸氧化态的四氢叶酸辅酶模型, 与亲核Grignard试剂作用, 将甲酸氧化态的一碳单元转移给亲核试剂, 成功地实现了6类具有潜在应用价值的环己基甲酮的绿色仿生合成, 其结构用元素分析、1H NMR、IR和MS等方法进行了表征, 并对反应机理和反应条件进行了讨论.     

Catalytic Asymmetric Phase‐Transfer Michael Reaction and Mannich‐Type Reaction of Glycine Schiff Bases with Tartrate‐Derived Diammonium Salts

Catalytic asymmetric Michael and Mannich‐type reactions of glycine Schiff bases with chiral two‐center organocatalysts, tartrate‐derived diammonium salts (TaDiASs), are described. On the basis of conformational studies, optimized TaDiASs with a 2,6‐disubstituted cyclohexane spiroacetal were newly designed. These TaDiASs catalyzed the asymmetric Michael and Mannich‐type reactions of glycine Schiff bases with higher enantioselectivity than previous catalysts. In the Mannich‐type reaction, aromatic N‐Boc‐protected imines (Boc=tert‐butoxycarbonyl) as well as enolizable alkyl imines were applicable. As a synthetic application of the catalytic asymmetric Mannich‐type reaction with the optimized TaDiASs, we developed a catalytic asymmetric total synthesis of (+)‐nemonapride, which is an antipsychotic agent.     

Synthesis and antifungal evaluation of 1-aryl-2-dimethyl- aminomethyl-2-propen-1-one hydrochlorides

The development of resistance to current antifungal therapeutics drives the search for new effective agents. The fact that several acetophenone-derived Mannich bases had shown remarkable antifungal activities in our previous studies led us to design and synthesize some acetophenone-derived Mannich bases, 1-8 and 2-acetylthiophene-derived Mannich base 9, 1-aryl-2-dimethylaminomethyl-2-propen-1-one hydrochloride, to evaluate their antifungal activities. The designed chemical structures have α,β-unsaturated ketone moieties, which are responsible for the bioactivities of the Mannich bases. The aryl part was C?H?(1); 4-CH?C?H? (2); 4-CH?OC?H? (3); 4-ClC?H? (4); 4-FC?H? (5); 4-BrC?H? (6); 4-HOC?H? (7); 4-NO?C?H? (8); and C?H?S(2-yl) (9). In this study the designed compounds were synthesized by the conventional heating method and also by the microwave irradiation method to compare these methods in terms of reaction times and yields to find an optimum synthetic method, which can be applied for the synthesis of Mannich bases in further studies. Since there are limited number of studies reporting the synthesis of Mannich bases by microwave irradiation, this study may also contribute to the general literature on Mannich bases. Compound 7 was reported for the first time. Antifungal activities of all compounds and synthesis of the compounds by microwave irradiation were also reported for the first time by this study. Fungi (15 species) were used for antifungal activity test. Amphotericin B was tested as an antifungal reference compound. In conclusion, compounds 1-6, and 9, which had more potent (2-16 times) antifungal activity than the reference compound amphotericin B against some fungi, can be model compounds for further studies to develop new antifungal agents. In addition, microwave irradiation can be considered to reduce reaction period, while the conventional method can still be considered to obtain compounds with higher reaction yields in the synthesis of new Mannich bases.     

从四氢叶叶酸辅酶模型合成麝香酮中间体2,1 5-十六二.酮

麝香酮是麝香中重要的具有生理活性的组分.自Ruzicka[1]确定其结构以来,化学家研究和发展了许多合成麝香酮的方法[2].Stoll[3]提出的由2,15-十六二酮经分子内环合后氢化得到麝香酮,其操作简便,但尚需解决2,15-十六二酮的来源问题.5,6,7,8-四氢叶酸辅酶在生物体内的功能和作用及仿生合成已成为仿生化学研究的重要课题[4].四氢叶酸辅酶在生物体内传递不同氧化态的-碳单元,当-碳单元处于甲酸氧化态时,活性部位是形成的咪唑啉环[5,6].因此,本文以咪唑啉盐作为四氢叶酸辅酶模型,与亲核试剂双格利雅试剂作用,仿生合成2,15-十六二酮.     

四氢叶酸模型化合物咪唑啉盐的基团转移反应

合成了2种四氢叶酸辅酶模型化合物咪唑啉盐7和8. 它们与双官能团亲核体作用, 分别完全转移了3个和5个碳单元; 化合物7与单官能团亲核体作用, 部分转移了3个碳单元; 以部分转移产物化合物17作为四氢叶酸甲醛态模型, 与胺类反应实现了带硝基的4个碳单元的完全转移; 并研究了模型化合物7的还原反应. 这些反应模拟并扩展了四氢叶酸辅酶在生物体内转移一碳单元的功能, 产生了几种新的合成方法和试剂, 可以应用于有机合成中.     

Utility and Synthetic Uses of Mannich Reaction: An Efficient Route for Synthesis of Thiadiazino‐[1,3,5][3,2‐a]benzimidazoles

The utilities of the Mannich reaction in synthetic organic chemistry are reviewed. The behaviors of Mannich reactions on several bifunctional heterocyclic compounds have been reported. A new class of heterocyclic compounds, thiadiazino[1,3,5][3,2‐a]benzimidazoles 12a–g, were obtained by reaction of 2‐mercaptobenzimidazole with primary aliphatic amines in a one‐step synthesis. An attempt to apply this reaction using primary aromatic amines lead to the formation of the well‐known Mannich bases 11a–g rather than the N‐substituted thiadiazines 13.     

Studies on organophosphorus compounds: Synthesis and reactions of [1,2,4,3]triaza‐phospholo[4,5‐a]quinoxaline derivative

2,4‐Bis‐(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane‐2,4‐disulfide (Lawesson's reagent) ( 1 ) reacted with 2‐hydrazino‐3‐methyl‐quinoxaline ( 2 ) to give [1,2,4,3]‐triazaphospholo[4,5‐a]quinoxaline derivative 3 . The Mannich reaction using different amines on compound 3 gave Mannich bases 4a–d . Also, compound 3 reacted with formaldehyde to give the corresponding 2‐hydroxymethyl derivative 5 , which upon reaction with thionyl chloride gave the corresponding chloromethyl derivative 6 . Treatment of compound 6 with some thiols yielded the corresponding sulfides 7a–d . Acylation of compound 3 gave acylated compounds 8a,b . Compound 9 , which was prepared through the reaction of compound 3 with ethyl cyanoacetate, was investigated as a starting material for the synthesis of some new heterocyclic systems 10–13 . Also, reaction of compound 9 with carbon disulfide and 2 equivalents of methyl iodide in a one‐pot reaction yielded the corresponding ketene‐S,S‐acetal 14 , which in turn reacted with bidentates to give some new heterocycles 15–17 . © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:520–529, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20473     

甲基酮香料的仿生合成新方法研究

四氢叶酸辅酶在生物体内的作用是转移不同氧化态的一碳单元, 当一碳单元处于甲酸氧化态时, 活性部位是具有五元环状结构的咪唑啉环. 模拟四氢叶酸辅酶转移一碳单元的反应, 以苯并咪唑甲基碘盐作为四氢叶酸辅酶甲酸氧化态模型, 以格利雅试剂甲基碘化镁作为接收一碳单元的亲核试剂, 将甲酸氧化态的一碳单元转移给甲基碘化镁, 成功合成了三种重要的甲基酮香料甲基己基酮、甲基壬基酮和甲基十一烷基酮, 其结构用元素分析, 1H NMR, IR和MS等方法进行了表征, 并对反应机理和反应条件进行了讨论, 为甲基酮香料提供了一种仿生合成新方法.     

COMBINATORIAL SYNTHESIS OF MANNICH BASES IN SOLUTION／POLYMER REAGENT WORKUP

This paper describes a combinatorial synthesis the mannich bases in Solution through the Mannich reaction using 3 ketones,5 amines and formaldehyde in solution and hydrochloride as a catalyst and then using a macroporous quarterized ammonium resin(CO32-form)as a scavenge agent to remove the acid catalyst when the Mannich reaction is completed.It was found by GC/MS analysis that the symmetrical ketone,such as acetone,in the Mannich reaction mainly produces one Mannich base;while the asymmetrical ketone,such as 2-pentanone,gives two.     

Synthesis and Reactivity of Mannich Bases. XVIII. Reaction of Dithiocarbamic Acid Salts With Mannich Bases Derived from Ortho-Hydroxyacetophenones

The reaction of Mannich bases derived from ortho-hydroxyacetophenones with N,N-dialkyldithiocarbamic acid salts result in the formation of the corresponding dithiocarbamic acid esters via an amine moiety replacement when the process is conducted in cold water. Attempts to carry out the synthesis in refluxing ethanol-water mixture led to the insertion of carbon sulfide at the C—N bond in Mannich bases. N-Aryldithiocarbamic acid salts afforded on reaction with the above-mentioned Mannich bases only bis-(2-(2-hydroxybenzoyl)ethyl)thioethers.     

芳香胺参加的Mannich反应——3-芳氨基-3-苯基-1-(4-溴苯基)丙酮的合成

文献报道过芳香胺与苯甲醛生成的Schiff碱可在少量相应的芳香胺盐酸盐或浓盐酸催化下制备Mannich碱(Ⅰ),所用的Schiff碱系事先合成,且产率较低(15-68.9％)。本文报导用4-溴苯乙酮、苯甲醛和芳香胺在少量浓盐酸催化下能直接发生Mannich反应,     

龙葵醛的新合成方法研究

龙葵醛是一种珍贵的香料 ,也是重要的化工原料 ,广泛应用于香料、医药、染料及农药等行业 .龙葵醛的工业生产以苯乙酮和一氯醋酸乙酯为原料 ,按 Darzens法合成[1,2 ] .苯乙酮与一氯醋酸乙酯在强碱作用下制得甲基苯基环氧丙酸酯 ,该酯经皂化、中和、水解成酸 ,再将该酸加热分解 ,得龙葵醛 .该方法操作比较复杂 ,产率和产品纯度也不高 .为了寻找产率高、纯度好且成本低的新制备方法已有广泛的研究 .Rivero等 [3]提出的 2 -甲基苯乙醇氧化法 ,尽管产率较高 ,但反应温度要在 -78℃ ,不利于工业化生产 .陈万之等[4 ] 利用各种铑螯合物作为催化剂…     

四环素C-2位Mannich反应的研究

报道了四环素C-2位与伯胺、仲胺反应形成Mannich碱的简便方法:四环素盐酸盐在甲醇和水溶液中与伯胺反应,生成二级Mannich碱;四环素在叔丁醇中与仲胺反应,生成三级Mannich碱。合成了10个化合物,其中8个未见报道,并对所合成化合物的结构进行了表征。     

Modern Variants of the Mannich Reaction

Important building blocks for the synthesis of drugs or natural products are found in Mannich bases and their derivatives. Modern variants of the Mannich reaction that expand the potential of the classical intermolecular reaction significantly and enable efficient control of the regioselectivity and stereoselectivity are therefore the topic of intensive research. Intramolecular reactions, in particular as part of domino reaction sequences, often afford astoundingly simple and elegant approaches to complex target compounds.