Diastereoselective synthesis of (2R,4R)-2-aryl-4-hydroxypyrrolidine: preparation of the side chain of novel carbapenem.

Improved synthesis of the trans-3,5-disubstituted pyrrolidin-3-ylthio side-chain of the novel carbapenem 1 was achieved via stereoselective reduction of the 1-aryl-1-butanone derivative 5 and successive intramolecular cyclization of the resulting chiral alcohol 6. The 1-aryl-1-butanone derivative 5 was obtained by a coupling reaction of protected 4-hydroxy-2-pyrrolidone with aryl-Grignard reagent.     

Lipase-catalyzed kinetic resolution of ethyl 3-aryl-3-hydroxypropionate: preparation of the side chain of a novel carbapenem,J-114,870

An optically active 3-aryl-3-hydroxypropionate 3a was prepared by lipase-catalyzed kinetic hydrolysis of a diastereomeric mixture of 3-aryl-3-(α-chloroacetoxy)propionate 6 in good conversion yield with adequate purity (>95% de). This enzymatic reaction proceeded with great efficiency as measured by reaction rate, chemical yield and stereoselectivity. The compound 3a was converted to J-114,870 1a, a novel ultra-broad spectrum carbapenem, without significant epimerization.     

Synthesis of chiral 1,5-disubstituted pyrrolidinones via electrophile-induced cyclization of 2-(3-butenyl)oxazolines derived from (1R,2S)- and (1S,2R)-norephedrine

Starting from (1R,2S)- and (1S,2R)-norephedrine, enantiomers of the corresponding 2-(3-butenyl)oxazolines were prepared in a two-step process. The cyclization of the intermediate alkenylamides with phenylselenyl bromide afforded cyclic imidates instead of the expected pyrrolidinones. The electrophile-induced cyclizations of 2-alkenyloxazolines with bromine or iodine produced diastereomeric mixtures of chiral 1,5-disubstituted pyrrolidinones. The ring closure of the all-cis (1R,2S,5R)-diastereomer 7 with NaH resulted in the tetrahydropyrrolo[2,1-b]oxazol-5-one derivative 18, which was alternatively prepared by the cyclocondensation of (1R,2S)-norephedrine with levulinic acid.     

Synthesis of a new carbapenem with a 6-methyl hydroxyacetate side chain

The synthesis of the 2-(4-pyridinylthio)-carbapen-2-em-3-carboxylic acid 1b, bearing a 6-methyl hydroxyacetate side chain, is described.     

Synthesis of alkenylquinolines and cyclization of (1-methyl-2-butenyl)quinaldines in polyphosphoric acid

The reaction of 2- and 4-alkenylanilines with paraldehyde gave 6- and 8-alkenylquinaldines. Heating 8-(1-methyl-2-butenyl)quinaldines in polyphosphoric acid leads to the formation of tricyclic compounds with isomerization of the alkenyl group.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1364–1366, October, 1990.     

Synthesis of some new 2-(3-aryl-1-phenyl-4-pyrazolyl)-benzoxazoles using hypervalent iodine mediated oxidative cyclization of Schiff's bases

Ten new 2-(3-aryl-1-phenyl-4-pyrazolyl)benzoxazoles have been synthesized by oxidative intramolecular cyclization of the corresponding Schiff's bases using iodobenzene diacetate in methanol as an oxidant.     

Synthesis and Quantification of 2-(Diethylamino)-N-(2-methylphenyl)acetamide Nitrate

Russian Journal of Organic Chemistry - A procedure for the synthesis of 2-(diethylamino)-N-(2-methylphenyl)acetamide nitrate (monomecaine) exhibiting a pronounced antiarrhythmic activity has been...     

Synthesis of 2(3H)-furanones via electrophilic cyclization

A variety of highly substituted 2(3H)-furanones are readily prepared from 3-alkynoate esters and the corresponding acids via electrophilic cyclization. Successful electrophiles in this process include I2, ICl, and PhSeCl. This highly efficient process proceeds under mild conditions, tolerates various functional groups, and generally provides substituted 2(3H)-furanones in good to excellent yields.     

Novel Synthesis of Some 1-N-(3-Fluoroadamantyl) Ureas

Some 1-N (3-fluoroadamantyl) ureas have been synthesized in good to excellent yields from 1-N- (3-fluoroadamantyl) isocyanate. The 3-fluoroadamantyl isocyanate has been prepared via the reaction of 1-N-(3-fluoroadamantyl) carboxamide with lead tetraacetate in N, N-dimethylformamide.     

Site-specific preparation of 3-fluoro-1-substituted-naphthalenes via a novel base-catalyzed cyclization reaction from (E)-monofluoroenynes

A novel cyclization reaction for the preparation of 3-fluoro-1-substituted-naphthalenes is reported. (E)-Monofluoroenynes, which are prepared by Sonogashira coupling reaction from (Z)-1-bromo-1-fluoroalkenes, undergo cyclization to afford 3-fluoro-1-substituted-naphthalenes in good to excellent yields when treated with DABCO or DBU in refluxing N-methyl-2-pyrrolidinone (NMP). [reaction: see text]     

A practical and efficient preparation of the releasable naphthosultam side chain of a novel anti-MRSA carbapenem

A practical large-scale synthesis of the naphthosultam-based side chain of the anti-MRSA antibiotic 1 has been achieved in 29% overall yield over seven steps from 1-methylnaphthalene. The synthesis was completed without the use of protecting groups, featuring a novel naphthosultam annelation, a chemoselective acid-catalyzed triflation, and the use of a novel naphthosultam dianion to effect functionalization through benzylic metalation.     

3-乙酰氨基苯乙酮的合成

苯乙酮经硝化、还原及酰化反应得到新型镇静催眠药佐匹配（Zaleplon)的重要中间体3－乙酰氨基苯乙酮。     

Practical synthesis of 1-aryl-6-(hydroxymethyl)-2-ketopiperazines via a 6-exo amide-epoxide cyclization

[reaction: see text] Chiral 1-aryl-6-(hydroxymethyl)-2-ketopiperazines can be prepared via an operationally simple, 6-exo epoxide ring-opening cyclization to form the ketopiperazine C6-N1 bond in high yields and with excellent enantiomeric purity.     

Studies on the Synthesis and Dynamic NMR Properties of 2-(Benzylidene amino)-N-[(R)-2-hydroxy-2-methyl-1-phenylpropyl]acetamide

An efficient method was employed for the preparation of 2-(benzylideneamino)-N-[(R)-2-hydroxy-2-methyl-1-phenylpropyl] acetamide utilizing optically pure (R)-5,5-dimethyl-4-phenyloxazolidin-2-one. This product showed interesting dynamic NMR properties for the methylene protons adjacent to the azomethine group (ΔG^? = 15.1 ± 0.1 kcal mol^-1).     

Alpha-N-acetylmannosamine (ManNAc) synthesis via rhodium(II)-catalyzed oxidative cyclization of glucal 3-carbamates

[reaction: see text] Glucal 3-carbamates 1 and 7 underwent oxidative cyclization with iodobenzene diacetate or iodosobenzene in the presence of Rh2(OAc)4, providing mannosamine 2-N,3-O-oxazolidinones. With iodosobenzene, incorporation of 4-penten-1-ol provided a readily separable anomeric mixture of n-pentenyl glycosides, with the anomers exhibiting pronounced differences in reactivity as glycosyl donors. N-acylation of the sugar oxazolidinones led to alpha-selective glycosyl donors for the elaboration of various 2-mannosamine frameworks. Alternatively, the anomeric n-pentenyl glycosides of N-Cbz 2-mannosamine oxazolidinones were converted separately to oxazolidinone-opened derivatives 28alpha and 28beta. These served as stereoconvergent glycosyl donors, and the alpha-linked products were readily advanced to a variety of N-acetylmannosamine (ManNAc) frameworks, using an intramolecular O-->N acetyl transfer as the final step.     

On the mechanism of the Leuckart reaction. Enantiospecific preparation of (1R,2R)- and (1S,2S)-N-(3,3-dimethyl-2-formylamino-1-norbornyl)acetamide

The Leuckart reaction of 2-norbornanone and (1R)-N-(3,3-dimethyl-2-oxo-1-norbornyl)acetamide ent-1b furnishes the expected N-(2-norbornyl)formamides 11 and ent-10 in good yield. Surprisingly, under the same reaction conditions, the (1R)-N-(7,7-dimethyl-2-oxo-1-norbornyl)acetamide 1a gives only 10, the enantiomeric form of the product obtained from ent-1b. An explanation of these results is given and a reaction mechanism, based on an unprecedented intramolecular transamidation, is proposed.     

Synthesis of novel tricyclic pyrimidine-fused 5,6-dihydrobenzodiazepines via a Pictet-Spengler-like cyclization

Novel pyrimidine-fused 5,6-dihydrobenzodiazepines were prepared via a Pictet-Spengler-like cyclization. It was based on the intramolecular electrophilic substitution of the phenyl ring of 5-amino-6-chloro-4-(N-methylanilino)pyrimidine 1 by the iminium intermediate formed with an aldehyde in one pot. The products may be further transformed by subsequent nucleophilic substitution of the chloro atom. This strategy may provide an efficient method to access a library of compounds based on privileged substructures that are of interest in drug discovery.     

From penicillin to penem and carbapenem. V Synthesis ofcarbapenam skeleton by (3 + 2) cyclization

The carbapenam derivatives were prepared by the new type of (3+2) cyclization²⁾ of 4-iodomethyl-2-azetidinones (1 and 6) and 2-thiosubstituted dimethylfumarate derivatives (2, R= CH₃, C₆H₅).     

Synthesis of unsymmetrical arylthiophenes and bithienyls via oxidative cyclization of 1,3-butadiene-1-thiols

Oxidative cyclization of 2-mercapto-5-aryl-2,4-pentadienoic acids with iodine produced the respective 5-aryl-2-thenoic acids. The method was also suitable for the synthesis of unsymmetrical substituted 2,2′-bithienyls, and 2,3′-bithienyls. The synthesis of 5-carboxy-2′-bromo-5′-phenyl-2,3′-bithienyl from benzal-acetone demonstrated that oxidative cyclization of 1,3-butadiene-1-thiols is a useful procedure for preparing 5′-aryl-2,3′-bithienyls from simple carbonyl compounds. Preferential ring bromination of 2-phenyl-4-methyl-thiophene with N-bromosuccinimide and a radical catalyst was also observed.     

Synthesis of pyridin-2(1H)-one derivatives via enamine cyclization

The nucleophilic vinylic substitution reaction of the aliphatic enaminone 3-dimethylamino-2-formyl acrylonitrile 1 with the nucleophiles malononitrile and ethyl cyanoacetate produced the two unusual reaction adducts 3a and 3b in good to moderate yield under milder reaction conditions. Upon reaction with aromatic amines, these adducts yielded enamines 4 and 5, which eventually cyclized in the presence of base to produce the novel pyridin-2(1H)-one derivatives 8 and 9.