A new and versatile one-pot synthesis of indol-2-ones by a novel Ugi-four-component-Heck reaction

A novel one-pot-synthesis of highly substituted indol-2-ones using a combination of Ugi and Heck reaction (U-4CR-Heck) is described. The synthesized indol-2-ones represent an interesting pharmacological scaffold with four potential points of diversity. Thus, this novel reaction-type is amenable to combinatorial high-throughput screening.     

Synthesis of Novel Maleonitrile Derivatives

The synthesis of four novel maleonitrile derivatives are described. New maleonitriles have been prepared by the reaction of different alkylhalides such as 3-bromopropionitrile, 1,3-dichloroacetone, α, α′-dibromoxylene, and p-nitrobenzylbromide with dithiomaleonitrile disodium salt. All novel compounds have cis-cyano groups and are characterized by IR, NMR spectroscopy, and elemental analysis.

     

A Novel Preparation of 4‐Phenylquinoline Derivatives in Ionic Liquids

A novel preparation of 4‐phenylquinoline derivatives through acid‐catalyzed Friedländer reaction in ionic liquid ([bmim][BF₄]) is described. The preparative procedure presented in this paper is operationally simple and environmentally benign. The reaction media and the catalyst used can be recovered and reused for at least four times without loss in the catalytic activity.     

Facile Synthesis of 3,3‐Dialkyl‐6‐phenyl‐imidazopyridinones

A series of novel 3,3‐dialkylated imidazopyridinones bearing 6‐aryl groups were designed as mimetics of active progesterone antagonists, 3,3‐disubstituted‐5‐arylindoles. The four‐step synthetic route is described. The key steps are base‐catalyzed cyclization, base‐catalyzed alkylation, and Suzuki coupling reaction.     

1,3-二-(3,3-二甲基-2-甲烯假吲哚)方酸菁染料的合成及其晶体

合成了两个新型方酸菁染料3和5。在酸催化下,2,3,3-三甲基假吲哚不需N-烷基化,可直接与方酸反应。反应过程中发生了明显的质子转移。结晶学数据表明,分子3的整体位于同一平面;溶剂苯规则地排布在方酸四碳环的周围,后者酷似电子陷阱。染料5有良好的水溶性。     

Organocatalytic Asymmetric 1,6‐Addition/1,4‐Addition Sequence to 2,4‐Dienals for the Synthesis of Chiral Chromans

A novel asymmetric organocatalytic 1,6‐addition/1,4‐addition sequence to 2,4‐dienals is described. Based on a 1,6‐Friedel–Crafts/1,4‐oxa‐Michael cascade, the organocatalyst directs the reaction of hydroxyarenes with a vinylogous iminium‐ion intermediate to give only one out of four possible regioisomers, thus providing optically active chromans in high yields and 94–99 % ee. Furthermore, several transformations are presented, including the formation of an optically active macrocyclic lactam. Finally, the mechanism for the novel reaction is discussed based on computational studies.     

Immunosuppressive polyketides from mantis-associated Daldinia eschscholzii

Polyketides with unknown architectures are highly desired for the discovery of new drugs and agrochemicals. Here, the mantis-associated Daldinia eschscholzii, a fungus known to produce immunosuppressants dalesconols A and B, was found to simultaneously generate four novel skeletons capable of shaping the unusual chemistry of the fungal polyketides, of which seven were structurally unique and substantially immunosuppressive. In particular, the scaled-up fermentation of the microbe enabled the structural characterization of minor or "transitional" intermediate polyketides that allowed the reasonable recognition of the four biosynthetic pathways initiated by condensations of four, five, six and eight acetate units, respectively. Furthermore, the decarbonylation reaction of triketone, as in the case of daeschol A, was described for the first time, in addition to the structural correction of sporothrin C and nodulone. The work provided a set of novel immunosuppressive molecules that are of significance to drug discovery.     

Synthesis of a novel azapseudodisaccharide related to allosamidin employing N,N''-diacetylchitobiose as a key starting material

Design and synthesis of a potential chitinase inhibitor 4, related to allosamidin (2), is described. Radical cyclization mediated by tributyltin hydride was applied for the first time to chitobiose-derived oxime ethers 9a,b to give four stereoisomers of an aminocyclopentane derivative connected to an N-acetyl-D-glucosamine residue at C-1 position. The major isomer 10b was efficiently converted into a novel pseudodisaccharide 4 via a series of cyclic-guanidine formation reaction.     

Synthesis of a new chiral organocatalyst derived from (S)-proline containing a 1,2,4-triazolyl moiety and its application in the asymmetric aldol reaction. Importance of one molecule of water generated in situ

A simple and efficient preparation of a novel chiral derivative of (S)-proline containing a 1,2,4-triazolyl moiety is described. The high-yielding synthetic protocol includes the use of microwave irradiation to afford new chiral pyrrolidine derivatives in high yield. Our triazolyl-containing heterocycle was evaluated as organocatalyst (10 mol% load, under neat reaction conditions) in the enantioselective aldol reaction between four different types of ketones and a variety of aryl aldehydes. Good results in terms of enantioselectivity and chemical yield were observed under solvent-free reaction conditions and in the absence of any additive. Evidence is provided for the involvement of the water molecule generated upon enamine formation in the transition state of the aldol reaction.     

Rhodium‐Catalyzed Arylative Cyclization for the Enantioselective Synthesis of (Trifluoromethyl)cyclobutanols

A rhodium‐catalyzed cyclization of 1‐(trifluoromethyl)‐4‐alkyn‐1‐ones with arylboronic acids is described to yield a novel class of small rings: (trifluoromethyl)cyclobutanols bearing an exocyclic double bond. The use of a rhodium/chiral diene complex allowed the reaction to proceed under mild conditions, often with high enantioselectivity. An X‐ray crystal structure was obtained confirming the formation of the four‐membered ring products.     

A new asymmetric synthesis of (2S,3R,4R,5S)-trihydroxypipecolic acid

A novel four step synthesis of enantiomerically pure (2S,3R,4R,5S)-trihydroxypipecolic acid, starting from readily available materials, that is, condensation products of (R)-(−)-phenylglycinol with a mesotrihydroxylated glutaraldehyde, is described. The scope and limitations of the reaction have also been investigated.     

Total synthesis of (+)-zaragozic acid C

A total synthesis of (+)-zaragozic acid C is described. Key features of the synthesis are the use of a double Sharpless asymmetric dihydroxylation reaction of diene 6 to control stereochemistry at four contiguous stereocenters from C3 to C6; the introduction of the C1-side chain by reaction between the anion derived from the dithiane monosulfoxide 27 and the core aldehyde 12; a high yielding, acid-mediated simultaneous acetonide deprotection-dithiane removal-ketalization procedure leading exclusively to the 2, 8-dioxabicyclo[3.2.1]octane core 34; and a novel triple oxidation procedure allowing installation of the tricarboxylic acid.     

Nigramides A-S, dimeric amide alkaloids from the roots of Piper nigrum

[structure: see text] Fifteen novel dimeric amide alkaloids possessing a cyclohexene ring, nigramides A-O (1-15), as well as four novel dimeric amide alkaloids possessing a cyclobutane ring, nigramides P-S (17-20), have been isolated from the roots of Piper nigrum. Their structures were elucidated on the basis of their spectroscopic data. The biosynthestic hypothesis of nigramides A-O (1-15) was proposed by an intermolecular Diels-Alder reaction from the corresponding monomeric amides. On the basis of this biosynthetic hypothesis, the first study of the thermal and Lewis acid mediated Diels-Alder reactions of piperine in different organic solvents and under solventless conditions is also described.     

Highly Regioselective and Diastereoselective,One‐Pot,Four‐Component Synthesis of Novel Spiroindenoquinoxalineindolizidine Derivatives

A one‐pot, four‐component procedure for the synthesis of novel spiroindenoquinoxalineindolizidines with high regioselectivity and diastereoselectivity from the 1,3‐dipolar cycloaddition of azomethine ylides, generated from indenoquinoxalines and pipecolinic acid, and chalcones is described. The reaction occurs under reflux of ethanol as a green solvent and in the absence of any catalyst. The cycloadducts are obtained purely without future purification. The regiochemistry and stereochemistry of resultant cycloadducts have been determined by several 2D‐NMR spectroscopic techniques and X‐ray single crystal diffraction.     

Dienyne RCM/Diels-Alder approach for the construction of novel steroid-like polycyclic systems

Our studies directed towards the preparation of novel steroid-like derivatives using RCM reactions are described. The strategy here described was applied to the construction of novel ring-inserted skeleton-expanded steroid analogs by combination of tandem ring-closing metathesis of lineal dienynes and Diels-Alder reaction.     

A new resin-bound universal isonitrile for the Ugi 4CC reaction: preparation and applications to the synthesis of 2,5-diketopiperazines and 1,4-benzodiazepine-2,5-diones

[reaction: see text] The preparation and synthetic applications of a novel resin-bound isonitrile are described. The resin is an example of a novel convertible isonitrile that can be utilized in the Ugi multicomponent reaction. Base-activation of the resin-bound Ugi product results in cleavage via formation of a N-acyloxazolidone that is then trapped as a carboxylic acid ester. This resin and the methodology described are suitable for synthesizing diversity libraries of 2,5-diketopiperazines and 1,4-benzodiazepine-2,5-diones.     

Organocatalytic approach toward the green one-pot synthesis of novel benzo[<Emphasis Type="Italic">f</Emphasis>]chromenes and 12<Emphasis Type="Italic">H</Emphasis>-benzo[5,6]chromeno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridines

An efficient tandem reaction approach is described to prepare novel benzo[f]chromenes from 2,3-dihydroxynaphthalene, malononitrile and aldehydes using 10 mol% guanidine hydrochloride as the catalyst under solvent-free conditions. The method was also extended to the preparation of novel 12H-benzo[5,6]chromeno[2,3-b]pyridines from 2-aminoprop-1-ene-1,1,3-tricarbonitrile instead of malononitrile under the same reaction conditions. The described one-pot three-component reaction is characterized by short reaction times, high-product yield, mild reaction conditions, simple workup procedure, and simple purification.     

Synthesis of 1,1-bis-phosphorus compounds from organoboranes

The facile synthesis of various P-C-P compounds is described, based on the reaction of phosphorus carbenoids with organoboranes, followed by reaction with phosphorus electrophiles. Using this approach, symmetrically and differentially substituted 1,1-bisphosphorus compounds can be obtained in good yields. A number of novel P-C-P motifs are described for the first time.     

One-pot synthesis of 4-heteroaryl-1,2-dihydro-3-benzazepines from 3,4-dihydroisoquinolinium salts or pseudo bases

A novel one-pot synthetic route to the poorly studied 4-heteroaryl-1,2-dihydro-3-benzazepine motif from 3,4-dihydroisoquinolinium compounds is described. The synthetic approach is based on heterocyclic ring expansion of isoquinoline substrates upon reaction with chloromethyl-substituted heterocycles. The scope and limitations of the reaction were investigated to give a series of novel heteroaryl-3-benzazepines.     

Microwave-assisted organic synthesis of a high-affinity pyrazolo-pyrimidinyl TSPO ligand

We herein report a dramatically improved total synthesis of the high-affinity translocator protein (TSPO) ligand DPA-714, featuring microwave-assisted organic synthesis (MAOS). Compared with previously described approaches, our novel MAOS method dramatically reduces overall reaction time without adversely effecting reaction yields. We envision that the described MAOS protocol may be suitably applied to high-throughput, diversity-oriented synthesis of novel compounds based on the pyrazolo-pyrimidinyl scaffold. Such an approach could accelerate the development of focused libraries of novel TSPO ligands with potential for future development as molecular imaging and therapeutic agents.