Recent developments in the combinatorial synthesis of nitrogen heterocycles using solid phase technology

Recognizing the potential of combinatorial chemistry to accelerate drug discovery and development, most pharmaceutical and related industries are seriously looking toward combinatorial synthesis of compounds in order to facilitate the identification of 'lead' molecules. In particular, solid phase synthesis is the core technology for combinatorial chemistry and is widely used for generating libraries of structurally related compounds. Since many drugs contain the nitrogen heterocyclic component and since heterocycles possess a high order of structural diversity, a precise overview of recent progress in the combinatorial synthesis of nitrogen heterocycles using solid phase methodology would be useful. Since the progress in solid phase synthesis of organic molecules has been reviewed regularly from 1992 to 1998, only the development of solid phase combinatorial synthetic approaches of small nitrogen heterocycles since 1999 will be reviewed here. This review describes the solid phase synthesis of azepanes, benzodiazepines, benzimidazoles, benzothiazepines, cinnolines, indolizines, beta lactams, oxazepins, oxazoles including benzisooxazoles, hydantoins, piperidines, pyrimidines, pyrazolones, quinolones, trizolopyridazines and thiazoles.     

Mechanistic Investigations into the Application of Sulfoxides in Carbohydrate Synthesis

The utility of sulfoxides in a diverse range of transformations in the field of carbohydrate chemistry has seen rapid growth since the first introduction of a sulfoxide as a glycosyl donor in 1989. Sulfoxides have since developed into more than just anomeric leaving groups, and today have multiple roles in glycosylation reactions. These include as activators for thioglycosides, hemiacetals, and glycals, and as precursors to glycosyl triflates, which are essential for stereoselective β‐mannoside synthesis, and bicyclic sulfonium ions that facilitate the stereoselective synthesis of α‐glycosides. In this review we highlight the mechanistic investigations undertaken in this area, often outlining strategies employed to differentiate between multiple proposed reaction pathways, and how the conclusions of these investigations have and continue to inform upon the development of more efficient transformations in sulfoxide‐based carbohydrate synthesis.     

Preparation of nanoparticles of silver halides,superconductors and magnetic materials using water-in-oil microemulsions as nano-reactors

Water-in-oil microemulsions have been used for the synthesis of a variety of nanoparticles since the technique was first introduced in 1982. In this paper we have reviewed several articles pertaining to the synthesis of nanoparticles in microemulsions and described in some detail our research efforts in the past decade in the field of synthesis of nanoparticles of silver halides, superconductors and magnetic materials using water-in-oil microemulsions as nano-reactors.     

Recent advances in microwave-assisted combinatorial synthesis and library generation

Progress and developments made in microwave-assisted combinatorial synthesis and library production since 2002 are reviewed. The use of microwave technology in both solution and solid phase synthesis is discussed with special reference to agrochemical applications where appropriate.     

A Convenient Route for the Preparation of Aromatic Aldehydes

Though a variety of methods^2–5 are available for the synthesis of aldehydes, this area continues to attract attention^6,7 since aldehydes are important intermediates in synthetic organic chemistry. In this communication we present a new route for the synthesis of aromatic aldehydes.     

Ammonia-free synthesis of 3-trifluoromethyl-3-phenyldiaziridine

An ammonia-free synthesis of 3-trifluoromethyl-3-phenyldiaziridine, an important intermediate in the synthesis of a widely used photolabel 3-trifluoromethyl-3-phenyldiazirine, is described. By avoiding the use of volatile, corrosive, and toxic anhydrous ammonia, the major hazard involved in the synthesis of this widely used photolabel is eliminated. Furthermore, this synthesis is convenient compared to the conventional route, since it is significantly less time consuming and, due to the absence of liquid ammonia, this method does not require the maintenance of low temperature for prolonged periods.     

Synthesis of Mono N-Substituted Guanylthioureas

A convenient method for the synthesis of mono N-substituted guanylthioureas in reasonable yields from readily available starting materials has been developed. In contrast to the previously published method, the use of highly noxious hydrogen sulfide is avoided. The method allows the rapid preparation of guanylthioureas since the synthesis of each requires only a single step from a common intermediate, the S-methylated derivative of dithiobiuret.     

用于CO2或CO加氢合成甲醇过程的高活性Cu/ZnO/Al2O3纳米纤维催化剂

 采用特殊的共沉淀法制备了一种在CO2加氢和CO加氢过程中都具有很高活性的Cu/ZnO/Al2O3纳米纤维催化剂. 与商业催化剂相比,该催化剂的CO2和CO转化率、甲醇选择性和甲醇时空产率高很多. 该合成方法不需要有机试剂和复杂的过程,因此生产成本低,容易实现.     

Gram scale synthesis of the glucuronide metabolite of ABT-724

A gram scale synthesis of the glucuronide metabolite of ABT-724 is reported. Glycosidic coupling between a trichloroacetimidate glucuronyl donor and a Cbz-protected hydroxypyridylpiperazine glycosyl acceptor is the key step in the synthesis, since attempts to directly glucuronidate the aglycon, aglycon derivatives, and other truncated glycosyl acceptors were unsuccessful. The route was used to produce 2.1 g of metabolite in eight steps from 2-chloro-5-hydroxypyridine in 21% overall yield.     

微流控技术在纳米合成中的应用

微流控技术具有微型化、集成化的特点,且所合成产物形貌和单分散性好,已经越来越多的被应用于纳米材料的合成中。 本文对微流体技术在纳米材料合成中的应用做了系统的阐述。 对微流控芯片中流体流动、混合机理进行了介绍,并详细介绍了微流控芯片的制作工艺,展望了微流体技术在合成纳米材料中应用前景。     

Die tödliche Brechnuss. Strychnin – von der Isolierung zur Totalsynthese

Strychnine, one of the most poisonous alkaloids, has fascinated scientists since its first isolation in 1818. It took over 130 years until its chemical structure was unequivocally determined and another 7 years until the first total synthesis by Robert B. Woodward was finished. Nowadays scientists are still developing new strategies for the synthesis of this fascinating complex compound. Some chemical aspects and personal accounts of synthesis #17 from 2010 are given.     

中国有机合成化学家的攀登

简要回顾了建国５０年、特别是近２０年来中国有机合成化学家们在于然产物及其类似物的合成方面所取得的若干具代表性的成就。     

低价钛在有机合成中的应用新进展

主要综述了近年来低价钛诱导的McMurry反应在有机合成中的应用新进展.     

与癌症相关的糖类抗原Globo-H六糖的全合成进展

Globo-H作为一种和乳腺癌、前列腺癌相关的复杂糖类抗原,其发现为糖类疫苗开发和癌症免疫治疗带来了机遇,但如何高效、高纯地获得合成糖类抗原,以供研究和临床应用,也向寡糖合成方法学提出了挑战.综述了1995年Danishefsky首次以糖烯组装策略全合成Globo-H以来的各种新方法,如:Schmidt的三氯乙酰亚胺酯法、Boons的双向糖苷化法、Wong的基于糖基给体活性差异的一锅煮策略、Seeberger的液相线性合成和固相自动组装法、Huang的多组份反复预活化一锅煮法和最新报道的酶法.就糖合成方法学而言,硫苷法依旧可称为"明星方法",糖烯、三氯乙酰亚胺酯和氟代糖也普遍采用,磷酸酯糖基给体在固相合成中的应用正显示出其新的活力.这些方法代表了当今糖化学的水平和发展趋势.     

Fawcettimine‐Type Lycopodium Alkaloids as a Driving Force for Discoveries in Organic Synthesis

Ever since the pioneering synthetic work reported by both Inubushi and Heathcock back in 1980s, the fawcettimine‐type Lycopodium alkaloids have continuously served as a driving force for discoveries in organic synthesis. In this personal account, we summarized our recent synthetic efforts towards the total synthesis of fawcettimine‐type Lycopodium alkaloids, along with a brief summary of relevant syntheses reported by others. Our discussions focus mainly on the key reactions applied during the synthesis of fawcettimine‐type Lycopodium alkaloids.     

Recent advances in liquid-phase combinatorial chemistry

In combination with high throughput screening, combinatorial organic synthesis of large numbers of pharmaceutically interesting compounds may revolutionize the drug discovery process. Although combinatorial organic synthesis on solid supports is a useful approach, several groups are focusing their research efforts on liquid-phase combinatorial synthesis by the use of soluble polymer supports to generate libraries. This macromolecular carrier, in contrast to an insoluble matrix, is soluble in most organic solvents and has a strong tendency for precipitation in particular solvents. Liquid-phase combinatorial synthesis is a unique approach since homogeneous reaction conditions can be applied, but product purification similar to the solid-phase method can be carried out by simple filtration and washing. This method combines the positive aspects of classical solution-phase chemistry and solid-phase synthesis. This review examines the recent applications (1995-1999) of soluble polymer supports in the synthesis of combinatorial libraries.     

Purine and sugar chemistry on solid phase--100 years after the Emil Fischer's Chemistry Nobel Prize 1902

The Nobel Prize in Chemistry 1902 was given to Hermann Emil Fischer "in recognition of the extraordinary services he had rendered by his work on sugar and purine synthesis". This truly great chemist of all time named a group of bicyclic nitrogenous structures as purines, discovered the synthesis of glucose, fructose and mannose starting from glycerol, and further created the basis for glucoside-, amino acid-, and enzyme chemistry. To honour his discoveries, and to celebrate the 100 year since his Nobel Prize, we decided to write a short review article on the latest discoveries in the fields of purine/pyrimidine and sugar chemistry being performed on solid support. The review summarizes most of the material being published in the field since 1960, and ends by giving a picture of future directions for the field of drug discovery based on sugar and purine chemistry.     

Synthesis of Fluoro-, Monofluoromethyl-, Difluoromethyl-, and Trifluoromethyl-Substituted Three-Membered Rings

This Minireview describes recent advances toward the synthesis of fluoro-, monofluoromethyl-, difluoromethyl-, and trifluoromethyl-substituted three-membered rings such as cyclopropanes, aziridines, epoxides, episulfides, cyclopropenes, and 2 H-azirines. The main synthetic methodologies since 2016 for cyclopropanes and since 2010 for the other three-membered rings are reported.     

Palladium‐Catalyzed Migratory Insertion of Isocyanides: An Emerging Platform in Cross‐Coupling Chemistry

Isocyanides have been important building blocks in organic synthesis since the discovery of the Ugi reaction and related isocyanide‐based multicomponent reactions. In the past decade isocyanides have found a new application as versatile C₁ building blocks in palladium catalysis. Palladium‐catalyzed reactions involving isocyanide insertion offer a vast potential for the synthesis of nitrogen‐containing fine chemicals. This Minireview discusses all the achievements in this emerging field.     

Synthesis of New Bifunctional Bis(oxazolines) and Their Application in the Asymmetric Cyanosilylation of Aromatic Ketones

Catalytic asymmetric synthesis of tertiary cyanohydrins by the addition of cyanide to a wide range of ketones has important synthetic utility, since the resulting optically active cyanohydrins are important intermediates for the synthesis of a variety of valuable classes of chiral compounds. The application of oxazoline in asymmetric cyanosilylation has seldom reported in comparation with other reactions.[1] Recently, polymer-supported pyridine-bis(oxazoline) ytterbium complex was reported to catalyze cyanosilylation of benzaldehyde.