Stereospecific N-oxide-mediated monoprotection of trans-3,4-dihydroxypyrrolidine derivatives

We found that the syntheses of O-monosubstituted 1-N-alkyl-trans-3,4-dihydroxypyrrolidines, normally faces serious obstacles due to poorly reactive hydroxy groups as a consequence of the presence of a highly basic pyrrolidine nitrogen atom, but that they can be obtained easily in high yields by conversion of 1-N-alkyl-trans-3,4-dihydroxypyrrolidines into the corresponding N-oxides. N-Oxidation leads to the loss of the pyrrolidine nitrogen atom basicity and discrimination in the reactivity of the originally equivalent hydroxy groups by at least one order of magnitude. The reaction of N-oxide derivatives with DMTrCl or TBDPSCl then proceeds in an almost quantitative yield, rapidly, and stereospecifically on the hydroxy group which is in a cis-position to the N-oxide oxygen atom. In contrast to the TBDPS derivative, the DMTr derivative could be easily deoxygenated with triphenylphosphine in high yield. The structures of the products obtained were confirmed by 2D NMR experiments, and quantum-chemical calculations were performed to explain the reaction mechanism of the stereospecific course of the reaction.     

Asymmetric synthesis of trans-2,3-piperidinedicarboxylic acid and trans-3,4-piperidinedicarboxylic acid derivatives

Asymmetric syntheses of (2S,3S)-3-(tert-butoxycarbonyl)-2-piperidinecarboxylic acid (1b), (3R,4S)-4-(tert-butoxycarbonyl)-3-piperidinecarboxylic acid (2b), and their corresponding N-Boc and N-Cbz protected analogues 8a,b and 17a,b are described. Enantiomerically pure 1b has been synthesized in five steps starting from L-aspartic acid beta-tert-butyl ester. Tribenzylation of the starting material followed by alkylation with allyl iodide using KHMDS produces the key intermediate 5a in a 6:1 diastereomeric excess. Upon hydroboration, the alcohol 6a is oxidized, and the resulting aldehyde 7 is subjected to a ring closure via reductive amination, providing 1b in an overall yield of 38%. Optically pure 2b has been synthesized beginning with N-Cbz-beta-alanine. The synthesis involves the induction of the first stereogenic center using Evans's chemistry and sequential LDA-promoted alkylations with tert-butyl bromoacetate and allyl iodide. Further elaboration by ozonolysis and reductive amination affords 2b in an overall yield of 28%.     

Synthesis of dipeptide derivatives of 3,4-substituted 7-hydroxycoumarins

Coumarins modified with dipeptides were prepared by condensation of N-hydroxysuccinimide esters of 2-(3,4,8-substituted-2-oxo-2H-7-chromenyloxy)-and 2-(3,4-substituted-7-methyl-2-oxo-2H-5-chromenyloxy)acetic and-propionic acids with amino acids and dipeptides. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 239–242, May–June, 2008.     

A novel synthesis of cis-3,4-disubstituted cyclopentanones

A new method for the stereospecific synthesis of cis-3,4-disubstituted cyclopentanones is described.     

Facile preparation of 3-substituted 2-quinazolinones via electrogenerated base

A new series of 3,4-disubstituted quinazolin-2-ones, with potential T-type calcium channel antagonist activity, and new 4-methylene-quinazolin-2-ones, promising catalysts as N-heterocyclic olefins, have been prepared in good yield by a simple reaction between 2-aminobenzophenone, or 2-aminoacetophenone, and cyanomethyl anion electrogenerated by acetonitrile reduction at a graphite electrode, followed by the addition of different organic isocyanates and subsequent heterocyclization.     

The preparation and evaluation of 1-substituted 1,2,3,4-tetrahydro- and 3,4-dihydro-beta-carboline derivatives as potential antitumor agents

A series of 1-substituted 1,2,3,4-tetrahydro- and 3,4-dihydro-beta-carboline derivatives have been synthesized and evaluated for antitumor activity against murine P-388 and human tumor cell lines, KB-16, A-549 and HT-29. All of the compounds prepared, except for 19, showed significant cytotoxicity. Among them, compound 29 exhibited the most potent activity against all tested tumor cell lines. There was an apparent lack of correlation regarding cytotoxicity between 1,2,3,4-tetrahydro- and 3,4-dihydro-beta-carbolines. This study is the first to discover compound 29 as a potential lead for the development of future anticancer agents. The mode of inhibition for compound 29 was proposed.     

2-取代-环戊烯酮及其衍生物的简易合成

本文报道以2-氯环戊酮的加成重排反应合成2-取代环戊酮。如再引入硫硫双键,则可合成2-取代环戊烯酮。取代环戊酮和取代环戊烯酮是合成药物和合成香料的重要中间体。     

Reverse inductive effect in the series of trans-3,4-disubstituted thiolane 1,1-dioxides

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, p. 993, July, 1990.     

Si-methyl(fluoro)-substituted derivatives of trans-1, 2-disilylethylene

Conclusions The treatment of trans-l, 2-disilylethylene derivatives of type (CH₃)_3-nXnSiCH = CHSi(CH₃)₃-_mX_m, where X=Cl or OCH₃, and n, m=1-3, with 40% HF gave the corresponding fluoro derivatives (CH₃)₃-_nF_nSiCH=CHSi(CH₃)₃-_mF_m in high yields.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1911–1913, August, 1981.     

A practical synthesis of trans-3-substituted proline derivatives through 1,4-addition

A practical four-step synthesis of 3-alkyl-, vinyl-, and aryl-substituted proline derivatives, which are important building blocks for conformationally restrained peptide analogs, was developed. The method relies on a Cu-catalyzed 1,4-addition of Grignard reagents to N-protected 2,3-dehydroproline esters, efficiently prepared in a new one-pot protocol. The 1,4-addition products are obtained with good trans-selectivity (dr 5:1 to 25:1). A nonracemic sample of N-Cbz-3-vinylproline (74% ee) was obtained using Evans oxazolidinone as a chiral auxiliary.     

Facile synthesis of 4-substituted 3,4-dihydrocoumarins via an organocatalytic double decarboxylation process

3,4-Dihydrocoumarins, considered to be valuable building blocks, have attracted considerable attention due to their various biological activities. Herein, we have documented an efficient and convenient double decarboxylation process for the synthesis of 4-substituted 3,4-dihydrocoumarin in moderate to excellent yields under mild reaction conditions (up to 98%).     

Synthesis of 3-substituted trans-2-oxadecalins and 1-substituted trans-2-oxahydrindanes

A study was carried out of the intramolecular cyclization of trans-1-methoxymethyl-2-(1-hydroxyalkyl)cyclohexanes and trans-1-methoxymethyl-2-(2-hydroxyalkyl)cyclohexanes by the action of acid chlorides of phosphorous, sulfurous and p-toluenesulfonic acids with the formation of 1-substituted trans-2-oxahydrindanes in low yields and 3-substituted trans-2-oxadecalins in high yields. A relationship has been established between the yields of the cyclization products and the nature of the halogenating agent. The cyclization does not proceed via an intermediate oxonium ion, but by means of an intermolecular electronic transition.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1865–1877, August, 1991.     

Synthesis of 1-substituted trans-2-thiahydrindanes and 3-substituted trans-2-thiadecalins

Methods of synthesis of 1-R-trans-2-thiahydrindanes and 3-R-trans-2-thiadecalins from trans-1-methoxymethyl-2-chlorocyclohexane have been developed. The order of the chromatographic elution of the isomeric sulfides formed has been found. The configurations of the compounds have been established by¹H and¹³C NMR spectroscopy. The characteristics of the intermediate and final compounds are given. The splitting of 1-R-trans-2-oxahydrindanes and 3-R-trans-2-oxadecalins by the PBr₃/conc. HBr system has been effected.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1877–1884, August, 1991.     

Synthesis and antihypertensive properties of a novel series of 3-substituted amino-s-triazolo[3,4-α]phthalazine derivatives

A novel series of 3-substituted amino-s-triazolo[3,4-a]phthalazine derivatives has been synthesized by the one-pot cyclodesulfurization reactions utilizing 1-hydrazinophthalazine, alkyl, aryl, or aralkylisothiocyanates and dicyclohexylcarbodiimide (DCCD) mixtures. The products did not exhibit any antihypertensive properties. Their pmr and mass spectral analysis is given.     

New method for preparation of α-substituted acrylonitrile derivatives

The method for the preparation of α-substituted acrylonitrile derivatives by the quaternization of the nitrogen atom of both Me₂N groups in the corresponding substituted 3-(dimethylamino)propanal dimethylhydrazones followed by the Hoffman decomposition of the resulting diiodides was developed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1707–1709, September, 1999.     

Aminoethyl derivatives of 4-substituted pyrazolo[3,4-d]pyrimidines

New 3-aminoethyl derivatives of pyrazolo[3,4-d]pyrimidine were synthesized by reduction of 3-cyanomethylpyrazolo[3,4-d]pyrimidines with hydrazine hydrate in the presence of Raney nickel in alcohol.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 846–847, June, 1972.     

NMR study of 5-substituted pyrazolo[3,4-c]pyridine derivatives

Substituted pyrazolopyridines are potent inhibitors of phosphodiesterases and cyclin-dependent kinases. In this study, NMR was used to investigate the potential N1-H and N2-H tautomerism of 5-substituted pyrazolo[3,4-c]pyridine derivatives. Six compounds were fully characterized by using (1)H, (13)C, and (15)N chemical shifts and indirect (1)H--(13)C and (1)H--(15)N coupling constants. The (1)H NMR spectra were measured over a broad range of temperatures. All of the compounds were shown to exist predominantly in the N1-H tautomeric form. Complementary quantum-chemical calculations of the chemical shieldings and indirect spin-spin couplings support the structural conclusions drawn.     

Synthesis and structure of diastereomeric trans-3,4-diamino-2,2,6,6-tetramethylpiperidine1-oxyl derivatives

The reaction of 3,4-diamino-2,2,6,6-tetramethylpiperidine-1-oxyl with (1S)-(+)-camphor-10-sulfonyl chloride gives a mixture of diastereomeric 4-monosulfonylamino derivatives. The products of their acylation have been obtained. The 3,4-bis-[(1S)-camphor-10-sulfonylamino] derivative was synthesized and resolved to individual diastereomers. For one of them thetrans relationship of the 3- and 4-substituents and the absolute (3S,4R)-configuration were established by X-ray structural analysis.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 367–372, February, 1993.