Copper‐Catalyzed Three‐Component Synthesis of 2‐Iminodihydrocoumarins and 2‐Iminocoumarins

An efficient synthesis of N‐sulfonyl‐substituted 2‐imino‐3,4‐dihydrocoumarins and 2‐iminocoumarins via a copper‐catalyzed multicomponent reaction of sulfonyl azides with terminal alkynes and β‐(ortho‐hydroxyphenyl)‐α,β‐unsaturated ketones or ortho‐hydroxyphenylpropiolates has been developed. The cascade process involves trapping the keteimine by a nucleophilic addition and an intramolecular Michael addition. This methodology could well be extended to the concise synthesis of the polysubstituted piperidine scaffold.     

A Simple Copper‐Catalyzed Cascade Synthesis of 2‐Amino‐1H‐indole‐3‐carboxylate Derivatives

We have developed a simple and efficient copper‐catalyzed method for the synthesis of 2‐amino‐1H‐indole‐3‐carboxylate derivatives via cascade reactions of substituted N‐(2‐halophenyl)‐2,2,2‐trifluoroacetamide with alkyl 2‐cyanoacetate or malononitrile under mild conditions, and the method is of wide practical application.     

Facile Palladium‐Catalyzed Synthesis of 3‐Arylpyrazolo[1,5‐a]pyrimidines

An efficient palladium‐catalyzed synthesis of 3‐arylpyrazolo[1,5‐a]pyrimidines has been investigated. The key step in the synthesis is a Suzuki biaryl coupling of 3‐bromo‐2,5‐dimethyl‐7‐aminopyrazolo[1,5‐a]pyrimidines with arylboronic acids to provide 3‐arylpyrazolo[1,5‐a]pyrimidines in moderate to good yield. The synthetic utility of this methodology has been demonstrated by a concise and convergent synthesis of R121920, a potent CRHR₁ antagonist recently undergoing clinical evaluations.     

Enantioselective Synthesis of cis‐4‐Formyl‐β‐lactams via Chiral N‐Heterocyclic Carbene‐Catalyzed Kinetic Resolution

An efficient synthesis of optically pure cis‐4‐formyl‐β‐lactams (up to 99% ee) by a chiral NHC‐catalyzed ring expansion reaction has been realized, featuring the ready availability of both the substrate and the catalyst, and the mild reaction conditions. The current method is also suitable for the synthesis of enantioenriched 4‐formyl‐β‐lactams and succinimides containing quaternary carbon centers.     

Enzymatic Synthesis of 1‐Alkyl‐2‐hydroxy‐sn‐glycero‐2,3‐cyclic‐phosphate Using a Novel Lysoplasmalogen‐Specific Phopholipase D

Many phospholipase Ds (PLDs) are known to catalyze transphosphatidylation as well as hydrolysis of phospholipids. Transphosphatidylation of lysoplasmalogen (LyPls)‐specific phospholipase D (LyPls‐PLD), which catalyzes hydrolysis of ether lysophospholipids such as LyPls and 1‐hexadecyl‐2‐hydroxy‐sn‐glycero‐3‐phosphocholine (Lyso‐PAF), still remains unclear. This study aims to reveal the transphosphatidylation activity of LyPls‐PLD, that is, the production of cyclic ether lysophospholipid. The enzymatic reaction is conducted in a buffer system, and the reaction products of a novel LyPls‐PLD from Thermocrispum sp. are investigated using mass spectrometry (MS). MS analyses demonstrate the reaction products to consist of 100% 1‐hexadecyl‐2‐hydroxy‐sn‐glycero‐2,3‐cyclic‐phosphate (cLyPA) and choline from Lyso‐PAF; however, 1‐alkenyl‐2‐hydroxy‐sn‐glycero‐2,3‐cyclic‐phosphate from 1‐O‐1′‐(Z)‐octadecenyl‐2‐hydroxy‐sn‐glycero‐3‐phosphocholine and 1‐O‐1′‐(Z)‐octadecenyl‐2‐hydroxy‐sn‐glycero‐3‐phosphoethanolamine is not produced. These results are expected to help in elucidating the catalytic mechanism of LyPls‐PLD, that is, the rate‐limiting step, and indicate LyPls‐PLD to be useful for the one‐pot synthesis of cLyPA. Practical Applications: A novel phospholipase D, LyPls‐PLD, can exclusively synthesize cLyPA from Lyso‐PAF using a one‐step enzymatic reaction without an organic solvent. cLyPA could be expected to show bioactivities similar to those of cyclic phosphatidic acid, which promotes normal cell differentiation, hyaluronic acid synthesis, antiproliferative activity in fibroblasts, and inhibitory activity toward cancer cell invasion and metastasis.     

One‐Pot Synthesis of Triazolothiadiazepine 1,1‐Dioxide Derivatives via Copper‐Catalyzed Tandem [3+2] Cycloaddition/N‐Arylation

A practical and efficient synthesis of triazolothiadiazepine‐1,1‐dioxide derivatives via copper‐catalyzed [3+2] cycloaddition, followed by N‐arylation is described. The method is also applicable to the synthesis of indoline‐ and thiophene‐fused triazolothiadiazepine 1,1‐dioxide derivatives.     

Synthesis and reactive features of a terpolymer: Poly(N‐vinyl‐2‐pyrrolidone‐co‐vinyl acetate‐co‐glycidyl methacrylate)

A polyvinyl pyrrolidone terpolymer system is described that can be chemically cross‐linked at moderate, 70–100°C, temperatures. The system has significant potential for development of durable long‐lasting pyrrolidone coatings in a wide range of applications, particularly in water filtration membrane construction where leaching is an unresolved, serious problem. The synthesis of the terpolymer, poly(N‐vinyl‐2‐pyrrolidone‐co‐vinyl acetate‐co‐glycidyl methacrylate), by free radical polymerization is described. The reactive features of this terpolymer are presented in the context of acidic anhydride curing. In a polar aprotic solvent, the terpolymer is reacted with poly(methyl vinyl ether‐co‐maleic acid) and cured thermally. Key aspects of the terpolymer synthesis and the acid anhydride cross‐linking reaction using DSC, rheology, FTIR, and a small molecule model system to study the cross‐linking chemistry are presented. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Alkylzinc‐Mediated Addition of Alkynes to N‐Tosylaldimines: Enantioselective Synthesis of (E)‐(2‐En‐3‐ynyl)‐amines

An alkylzinc‐mediated simple and efficient procedure for the catalytic enantioselective synthesis of N‐tosyl‐(E)‐(2‐en‐3‐ynyl)‐amines has been developed. The method works well with various N‐tosylaldimines and alkynes.     

Synthesis of (all‐rac)‐α‐Tocopherol Using Fluorinated NH‐Acidic Catalysts

The synthesis of (all‐rac)‐α‐tocopherol starting from trimethylhydroquinone and isophytol using fluorinated NH‐acidic catalysts is described. Scope and limitations of this type of catalysts are discussed. Advantages of this new procedure are high yield and selectivity, no waste problem and mild reaction conditions. Best results in the synthesis of (all‐rac)‐α‐tocopherol (94% yield) using NH‐acidic compounds are obtained in polar solvents. The used catalyst could be recovered.     

Neuroprotective Effects of N‐Alkyl‐1,2,4‐oxadiazolidine‐3,5‐diones and Their Corresponding Synthetic Intermediates N‐Alkylhydroxylamines and N‐1‐Alkyl‐3‐carbonyl‐1‐hydroxyureas against in vitro Cerebral Ischemia

Herein we report the synthesis and neuroprotective effects of new N‐alkyl‐1,2,4‐oxadiazolidine‐3,5‐diones and their corresponding synthetic intermediates, N‐alkylhydroxylamines and N‐1‐alkyl‐3‐carbonyl‐1‐hydroxyureas, in an in vitro model of ischemia. We found five analogues that protect HT22 cells from death in the concentration range of 1–5 μM . Because members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the newly synthesized analogues. The results indicate that these compounds provide neuroprotection through distinct mechanisms of action.     

Silver‐Catalyzed Intramolecular Cyclization of o‐(1‐Alkynyl)benzamides: Efficient Synthesis of (1H)‐Isochromen‐1‐imines

An efficient avenue for the facile and atom‐economic synthesis of (1H)‐isochromen‐1‐imines has been developed, and a broad spectrum of substrates can participate in the process effectively to produce the desired products in good yields. Significantly, this is the first report of the synthesis of (1H)‐isochromen‐1‐imines that involves a silver(I)‐catalyzed, regiocontrolled intramolecular addition of the carbonyl group of the amide moiety towards an alkyne.     

Chemo‐enzymatic synthesis of poly(2,2,2‐trichloroethyl 10‐hydroxydecanate)‐block‐polystyrene combining enzymatic self‐condensation polymerization and ATRP

Enzymatic polymerization in a non‐natural environment is of interest as an environmentally friendly methodology as an alternative to the use of conventional chemical organometallic catalysts. Chemo‐enzymatic synthesis of the AB‐type diblock copolymer poly(2,2,2‐trichloroethyl 10‐hydroxydecanate)‐block‐polystyrene (PHD‐b‐PSt) was carried out by combining enzymatic self‐condensation polymerization (eSCP) and atom‐transfer radical polymerization (ATRP). Biocatalyst Novozyme 435 was successful in catalyzing the eSCP of a novel ω‐hydroxyester, i.e. 2,2,2‐trichloroethyl 10‐hydroxydecanate. The resulting ? CCl₃‐terminated PHD initiated the ATRP of styrene, a ‘living’/controlled radical polymerization. The analysis of the hydrolysate from the copolymer proved the presence of a block copolymer structure. In addition, the well‐defined diblock copolymer PHD‐b‐PSt self‐assembled into nanoscale micelles in aqueous solution. The chemo‐enzymatic synthesis of diblock copolymer PHD‐b‐PSt was achieved by the combination of eSCP and ATRP. The structures and composition of the block copolymer were characterized by means of NMR, infrared and gel permeation chromatography measurements. Differential scanning calorimetry analysis showed that a microphase‐separation structure was formed in the copolymer, which was caused by the crystallization of the PHD segments. As investigated with atomic force microscopy and dynamic light scattering, these micelles had a mean diameter and a spherical shape. To our knowledge, this is the first example of a chemo‐enzymatic synthesis based on eSCP and ATRP. Copyright © 2007 Society of Chemical Industry     

Palladium‐Catalyzed Dienylation of Haloalkynes using 2,3‐Butadienyl Acetates: A Facile Access to (1Z)‐1,2‐Dihalo‐ 3‐vinyl‐1,3‐dienes

A highly efficient and stereoselective method for the synthesis of (1Z)‐1,2‐dihalo‐3‐vinyl‐1,3‐dienes featuring palladium‐catalyzed coupling of haloalkynes and 2,3‐butadienyl acetates was developed. The resulting products were smoothly converted into cis‐1,2‐dihalostyrene derivatives using the Diels–Alder/aromatization sequence.     

Highly Regio‐ and Stereoselective Iodohydroxylation of Non‐ Heteroatom‐Substituted Allenes: An Efficient Synthesis of 4‐[3′‐Hydroxy‐2′‐iodoalk‐1′(Z)‐enyl]‐2(5H)‐furanone Derivatives

An efficient protocol for the highly regio‐ and stereoselective synthesis of 4‐(3′‐hydroxy‐2′‐iodoalk‐1′(Z)‐enyl)furan‐2(5H)‐one derivatives via selective iodohydroxylation of non‐heteroatom‐substituted allenes, i.e., 4‐allenyl‐2(5H)furanones, has been developed. The regio‐ and stereoselectivity of this reaction may be controlled by the electronic and steric effects of the furanone ring.     

Asymmetric Synthesis of 2‐Substituted Dihydrobenzofurans and 3‐Hydroxydihydrobenzopyrans through the Enantioselective Epoxidation of O‐Silyl‐Protected ortho‐Allylphenols

The Shi‐type epoxidation of O‐tert‐butyldiphenylsilyl (TBDPS) protected o‐allylphenols serves as an efficient strategy to construct the dihydrobenzofurans and dihydrobenzopyrans in up to 97% ee. This methodology led to the enantioselective synthesis of (+)‐marmesin, (−)‐(3′R)‐decursinol, and (+)‐lomatin.     

Single‐step synthesis of a radically polymerizable 1,1′‐bi‐2‐naphthol derivative for asymmetric catalysis

A new polymerizable 1,1′‐bi‐2‐naphthol derivative for polymer‐supported catalytic asymmetric synthesis is presented. The synthesis is conducted within a single reaction step, which is a major advantage over other approaches presented in the literature. The ligand‐bearing polymer is prepared through copolymerization with N‐isopropylacrylamide. Preliminary experiments on the utility in catalytic asymmetric alkylation reactions reveal the accessibility and activity of the polymer‐attached catalysts. The stereoselectivity of the reaction is found to be somewhat lower than for reactions performed in the presence of free 1,1′‐bi‐2‐naphthol, and thus requires further optimization. The enantiomeric excess of the reaction products was determined via ¹H NMR spectroscopy after chiral derivatization with (R)‐α‐methylbenzyl isocyanate. © 2015 Society of Chemical Industry     

Synthesis of ethyl propionate catalyzed by poly(N‐AEAAm‐co‐AAc)‐cl‐MBAm hydrogel‐immobilized lipase of Bacillus coagulans MTCC‐6375

A purified alkaline thermotolerant bacterial lipase of Bacillus coagulans MTCC‐6375 was efficiently immobilized onto poly(N‐AEAAm‐co‐AAc‐cl‐MBAm)‐hydrogel at pH 8.5 and at temperature 55°C in 16 h. The hydrogel‐bound matrix possessed 1.04 U/g (matrix) lipase activity with a specific activity of 1.8 U/mg of protein. The immobilized lipase resulted in formation of 52.5 mM of ethyl propionate (52% conversion) at 55°C in 9 h in n‐nonane. Ethanol and propionic acid when used in a ratio of 300 : 100 mM, respectively, in n‐nonane along with 10 mg of hydrogel‐bound lipase resulted in optimal synthesis of ethyl propionate (82.5 mM). Addition of molecular sieves (3 Å, 0.7 g/reaction volume) further enhanced the conversion rate to 82.4% resulting in 83.5 mM of ethyl propionate. Incubation temperature below or above 55°C had a marked effect on the synthesis of ethyl propionate. However, esterification performed in n‐heptane at 65°C resulted in 87.5 mM of ethyl propionate with a conversation rate of 89.3%. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Generation of 11‐Fluoro‐11H‐indeno[1,2‐c]quinolines via a Palladium‐Catalyzed Three‐Component Reaction of 2‐Alkynylbromobenzenes, 2‐Alkynylanilines,and N‐Fluorobenzenesulfonimide

A novel and efficient synthesis of 11‐fluoro‐11H‐indeno[1,2‐c]quinolines has been developed via a palladium‐catalyzed three‐component reaction of 2‐alkynylbromobenzenes, 2‐alkynylanilines, and N‐fluorobenzenesulfonimide. The reaction works well with high selectivity. Additionally, the diversity and complexity could be easily introduced via a simple operation from readily available starting materials. In the meantime, a fluorine atom could be incorporated into the scaffold during the reaction process.     

A Desymmetrization Approach to the Enantiopure syn/anti‐1,5‐Diols via Hydrolytic Kinetic Resolution (HKR) of Functionalized meso‐Bis‐Epoxides: Further Elaboration to syn/syn‐1,3,5‐Triols and Application to the Formal Synthesis of Cryptocarya Diacetate

A new approach has been developed for the synthesis of enantiopure syn/anti‐1,5‐diols by desymmetrization of functionalized meso‐bis‐epoxides using hydrolytic kinetic resolution (HKR). The usage of this protocol was demonstrated by converting syn‐1,5‐diols into syn/syn‐1,3,5‐triols and its subseqent application to the formal synthesis of cryptocarya diacetate.