Synthesis of indole-5,6- and carbazole-2,3-dicarboxylic acid functional derivatives

Principal synthetic approaches to the synthesis of indole-5,6- and carbazole-2,3-dicarboxylic acid functional derivatives are considered. The first of them consists in the construction of the indole ring from simpler aromatic compounds containing carboxy groups, cyano groups, or an imide fragment with subsequent reductive cyclization of the compounds formed. The second approach is based on the modification of a pyrrole or an indole fragment by the introduction of different functional groups with subsequent intramolecular cyclization to the corresponding heterocycles.     

三组分串联反应一锅合成多环稠合的1,5-苯并二氮杂䓬化合物

以取代的邻苯二胺、1,3-环戊二酮或1,3-环己二酮(5,5-二甲基-1,3-环己二酮)、2,3-二羰基化合物为原料,无水乙醇为溶剂,对甲苯磺酸为催化剂,经2~5 h串联反应一锅合成43种新颖的1,5-苯并二氮杂?化合物,产率最高可达95%.该反应序列首先通过两次的亲核加成-脱水反应过程,形成分子内亚胺和烯胺结构的活性中间体,然后再经分子内的碳碳偶联环合-质子转移等过程,生成多环稠合的1,5-苯并二氮杂?目标化合物,实现了在一个反应体系中形成一个二氮杂七元环和四个新化学键(两个C—N,一个C=C,一个C—C).该方法操作简单,反应便捷,对环境友好,产率高,为1,5-苯并二氮杂?化合物的合成提供绿色环保,高效简便的合成思路.     

Recent advances in the application of sulfinic acids for the construction of sulfur-containing compounds

Sulfur-containing organic compounds display wide applications in the field of materials science, synthetic chemistry, and pharmaceutical industry. Thus, numerous synthetic strategies have been developed for the synthesis of sulfur-containing compounds in synthetic chemistry. In recent years, the utilization of sulfinic acids as versatile synthons has emerged as attractive and powerful approach to access various organosulfur compounds through sulfonylation, sulfinylation or sulfenylation reaction...     

Synthesis of Phenolic Compounds via Palladium Catalyzed C−H Functionalization of Arenes

Phenol and its derivatives are extremely useful compounds in organic synthesis, medicinal chemistry and material sciences. The synthesis of phenols involving selective construction of the C?O bond at a C?H bond of arenes using transition‐metal catalysis represents the most appealing strategy. Indeed, active research is currently going on for the synthesis of valuable phenolic compounds using a transition‐metal‐catalyzed C?H functionalization strategy. This short review summarizes recent advances on palladium‐catalyzed C?O bond forming reactions that enable direct access to phenolic compounds. These catalytic reactions proceed either via C?H esterification with trifluoroacetic acid/trifluoroacetic anhydride followed by in situ hydrolysis of the ester or via direct C?H hydroxylation. A brief analysis of substrate scope and limitation, reaction mechanism as well as synthetic utility of these reactions has been included.     

Synthesis of optically active 2-alkyl-3,4-iminobutanoic acids. Beta-amino acids containing an aziridine heterocycle

All four stereoisomers of 2-alkyl-3,4-iminobutanoic acid, a novel class of beta-amino acids bearing a chemically versatile aziridine ring, were synthesized starting with aspartic acid. The synthetic strategy involves the introduction of an alkyl group at the beta-position of fully protected optically active aspartic acid followed by the construction of an aziridine ring making use of the alpha-carboxylate and alpha-amino groups. The alpha-carboxylate was reduced to the corresponding alcohol, which was then subjected to cyclization to form an aziridine ring with the N-protected amino group. Removal of the protection groups yielded the target compounds.     

Synthesis of a fragment of bacterial cell wall

Cell wall is indispensable for survival of bacteria. This large molecular "mesh" encases the entire cytoplasm of bacteria, and it is comprised of repeating backbone units of N-acetyl-glucosamine (NAG)-N-acetyl-muramic acid (NAM). A pentapeptide is attached to each of the lactyl units of the N-acetyl-muramic acid. The cell wall has both cross-linked and non-cross-linked components. In the present paper, we have devised a synthetic route for the preparation of a fragment of the cell wall comprised of a tetrasaccharide (NAG-NAM-NAG-NAM), along with the two appended peptides. We also report the syntheses of three glycosyl donors (compounds 5, 7, and 9) and three glycosyl acceptors (compounds 4, 6, and 8) based on the d-glucosamine structure as a building unit. The synthetic strategy that is disclosed is generally useful in construction of other natural products containing the d-glucosamine as a building block.     

A practical synthesis of differentially protected 2-(hydroxymethyl)piperazines

An efficient and scalable synthesis of three differentially protected 2-(hydroxymethyl)piperazines is presented, starting from optically active and commercially available (2S)-piperazine-2-carboxylic acid dihydrochloride. These synthetic building blocks are useful in the preparation of biologically active compounds and as chemical scaffolds for the construction of combinatorial libraries.     

Selective Synthesis of Fluorine‐Containing Cyclic β‐Amino Acid Scaffolds

Fluorine‐containing organic molecules have generated increasing impact in drug research over the past decade. Their preparation and development of novel synthetic methods towards new types of fluorinated molecules among them of β‐amino acid derivatives has received large interest. Our research group have designed various highly selective and stereocontrolled methods for the construction of fluorine‐containing cyclic β‐amino acid derivatives. The synthetic approaches developed for the synthesis of various pharmacologically interesting cyclic β‐amino acid derivatives as monomers with multiple stereogenic centers might be valuable protocols for the access of other classes of organic compounds.     

Chemische eigenschaften und synthese-verfahren von 3-vinylindolen

Selectively functionalized 3-vinylindoles are mostly stable compounds, which may serve as potent building blocks for anellation of the indole nucleus, in particular for synthesis of carbazole alkaloides and to obtain pharmacologically active compounds. This review describes from a great number of the permanent increasing literature of vinylheterocycles the chemical properties, the most important principles of the synthetic methods and the synthetic applications of 3-vinylindoles. Among the synthetic methods to obtain 3-vinylindoles the classical condensation, the Wittig-Horner-/Wadsworth-Emmons-Olefination and the recently developed Pd-catalyzed vinylation should be considered as reliable standard methods. Depending on the special functionalization in the desired product some others methodologies are developed, so the thermolysis or the acid catalyzed ipso-cleavage of hetarylindolylethanes for deriving 1-hetaryl-1-indolylethenes.     

Construction of heterocyclic compounds by use of alpha-diazophosphonates: new one-pot syntheses of indoles and isocoumarins

[reaction: see text] alpha-Diazophosphonates, which have extremely useful properties from a synthetic point of view, are disclosed as 1,1-ambiphilic one-carbon building blocks for one-pot construction of various heterocyclic compounds. They are easily prepared and have higher stability by the effect of the phosphoryl group than corresponding alpha-diazocarbonyl compounds. Using this synthon, we have developed a novel, mild, and efficient synthetic method of 2,3-disubstituted indoles and 3,4-disubstituted isocoumarins.     

钯催化合成香豆素研究进展

香豆素是一类苯并六元含氧杂环类化合物,具有抗氧化、抗菌、抗炎等多种生理活性,受到人们的广泛关注。近年来不断有香豆素的新合成方法报道,特别是高效的过渡金属钯催化合成反应。本文综述了近20年来钯络合物催化合成香豆素骨架的研究进展,主要包括羰基化反应、炔烃芳基化反应、烯烃芳基化反应和偶联反应,以期为合成新型香豆素提供参考。     

13-cis-维A酰衍生物合成方法的改进

改进并建立了以4-二甲氨基吡啶(DMAP)-对甲苯磺酸盐为催化剂,二环己基碳酰亚胺(DCC)为缩合剂直接用13-cis-维A酸与醇、酚或胺合成13-cis-维A酰衍生物的方法。合成了8种新目标化合物,收率80%～95%,核磁共振氢谱和碳谱研究表明,13-cis-维A酰部分的构型均保持不变。合成方法彻底抑制了反应中N-异维A酰基脲的副反应,而且反应条件温和,对于极易异构化的13c-is-维A酸的酯化和酰胺化反应十分有利。     

Synthesis of Asebogenin and Balsacone A Precursor by a Novel Synthetic Strategy: Recent Opportunities for and Challenges of Total Synthesis of Balsacone A

One of the main areas of interest of synthetic organic chemistry is the rapid construction of small molecules with proven diverse biological activities for the development of new strategies to cure human health. In particular, the development of novel synthetic strategies is the most important option for reaching the molecular scaffolds of active molecules of natural origin. Balsacone A and asebogenin are compounds that exhibit a wide variety of important biological activities. In this respect, it has become very important to develop new strategies for the construction of biologically active natural and synthetic balsacone analogues. In particular, balsacone derivatives with hydroxy-substituted dihydrochalcone skeletons can be isolated from plant sources or obtained by hemi-syntheses using bio-sourced precursors. An efficient synthetic strategy to synthetically obtain balsacone A is the aim of the present study that considers the limited natural availability of these molecules as well as other factors, such as cost and time. Starting with phloroglucinol, a nine-step synthesis of the precursor of balsacone A was achieved at a 10% overall yield. Furthermore, asebogenin, which has a dihydrochalcone structure and plays a key role in the synthesis of balsacone A, was synthesised with a good yield.     

Halovinylene Carbonates in Organic Synthesis. New synthetic methods (2)

Monohalo- and dihalovinylene carbonates constitute a new class of cyclophiles which permit simultaneous introduction of masked α-hydroxyketo and α-diketo functions, respectively, into the cycloadducts. Demasking can be performed by simple hydrolysis. Solvolytic opening of the carbonate ring leads to glycolic acid derivatives in the case of the monohalo compounds and to glyoxylic acid derivatives with the dihalo compounds. Preparation of the title compounds, their potential as synthetic reagents, and the chemistry of their simple reaction products are surveyed from a preparative viewpoint.     

Recent advances in the synthetic chemistry of 1,5-benzothiazepines: A minireview

Benzothiazepine, a prominent “drug prejudice core”, is a heterocyclic moiety of immense importance due to its presence in a wide range of bioactive compounds. They act as a primary “biolinker” in diverse synthetic routes to obtain bioactive molecules and serve as important templates in synthetic and medicinal chemistry. They are known to possess a plethora of pharmacological activities, which include Ca²⁺ channel blockers, CNS acting agents, anti-HIV, ACE inhibitors, antimicrobial, antifungal, anticancer. Their promising behaviour as drug molecules led the scientific community to develop novel, mild, green, and highly efficient synthetic routes for their synthesis. The conventional synthesis generally involved the condensation of chalcones with 2-aminothiophenol in the presence of acid/base with high-temperature heating, mostly resulting in poor yields or mixtures. However, recent trends are replacing these conditions with mild and green conditions through organocatalysis or other methodologies. In this review, an attempt has been made by authors to summarize (a) Recent developments in the synthetic strategies of 1,5-benzoathiazepines and its derivatives (b) Conventional methods for the synthesis of 1,5-benzothiazepines including progress in the green chemistry routes (c) Applications of various metals and organocatalysts to achieve the enantioselective synthesis of title compounds.     

Anti-Cancer Potential of Synthetic Oleanolic Acid Derivatives and Their Conjugates with NSAIDs

Naturally occurring pentacyclic triterpenoid oleanolic acid (OA) serves as a good scaffold for additional modifications to achieve synthetic derivatives. Therefore, a large number of triterpenoids have been synthetically modified in order to increase their bioactivity and their protective or therapeutic effects. Moreover, attempts were performed to conjugate synthetic triterpenoids with non-steroidal anti-inflammatory drugs (NSAIDs) or other functional groups. Among hundreds of synthesized triterpenoids, still the most promising is 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), which reached clinical trials level of investigations. The new group of synthetic triterpenoids are OA oximes. The most active among them is 3-hydroxyiminoolean-12-en-28-oic acid morpholide, which additionally improves the anti-cancer activity of standard NSAIDs. While targeting the Nrf2 and NF-κB signaling pathways is the main mechanism of synthetic OA derivatives′ anti-inflammatory and anti-cancer activity, most of these compounds exhibit multifunctional activity, and affect cross-talk within the cellular signaling network. This short review updates the earlier data and describes the new OA derivatives and their conjugates in the context of modification of signaling pathways involved in inflammation and cell survival and subsequently in cancer development.     

亚砜叶立德在C—H键活化反应中的应用研究进展

过渡金属催化的导向C—H键活化反应具有反应效率高、选择性好、原子经济等优点,特别是卡宾前体参与的C—H活化反应已经发展为一种新颖的构筑碳碳键的合成策略.相比于传统的重氮化合物等卡宾前体,亚砜叶立德作为一种新型的卡宾前体,具有易于制备、性质稳定、操作安全等诸多优点,被广泛应用于C—H活化反应,可以便捷地转化成各种酰甲基化...     

A new strategy toward fused-pyridine heterocyclic scaffolds: Bischler-Napieralski-type cyclization, followed by sulfoxide extrusion reaction

Method development was completed for a new strategy to obtain fused-pyridine heterocyclic scaffolds. The synthetic route entails a Bischler-Napieralski-type reaction as the key step, followed by a sulfoxide extrusion reaction. The reactions of 3-amino-2-arylthiopyridines or 3-amino-4-arylthiopyridines and carboxylic acids promoted by a Lewis acid such as SnCl4 yielded novel tricyclic pyridobenzothiazepines, which could be readily converted to their corresponding oxidized products via a sequence of sulfur oxidations and eventually to benzonaphthyridines via a sulfoxide extrusion. The synthetic strategy provides an efficient way to access libraries of novel structurally diversified heterocyclic compounds with potential pharmaceutical or biological activities.     

Synthetic Strategies for Fused Benzothiazoles: Past,Present, and Future

Benzothiazole is used as a building block in organic synthesis, which serves as a key template for the development of various therapeutic agents and shows a wide spectrum of activities. The attractive application of benzothiazole in organic synthesis is undoubtedly due to the highly reactive C-2 amino group, which is responsible for the change in its bioactivity. The construction of a poly-heterocyclic compound with the fused hetero-systems has attracted increasing attention because of the diverse range of potential therapeutic activities. Significant efforts have been undertaken to exploit different synthetic routes to these compounds. This article gives a comprehensive account of the synthetic utility of benzothiazole employed in the design and synthesis of different types of compounds containing fused heterocyclic rings with greater emphasis on recent literature.     

Carbon‐Carbon and Carbon‐Heteroatom Bond Formation Reactions Using Unsaturated Carbon Compounds

The carbon‐carbon and carbon‐heteroatom bond formation reactions are considered as a fundamental tool in synthetic organic chemistry. They have been effectively utilized in the synthesis of medicinally significant molecules, agrochemicals and valuable compounds in material sciences. This has been primarily enabled by highly efficient protocols arising from divergent mechanistic pathways. In this personal account, we aim to discuss some recent advances in carbon‐carbon or carbon‐heteroatom bond formation reactions to which our group has actively contributed. More specifically, this record focuses on the use of unsaturated carbon compounds for the construction of C?C and C?X bonds.