N1- and C6-substituted adenines: a regioselective and efficient synthesis

New and efficient methods for the synthesis of N1-substituted and C6-substitued adenines were developed from the easily accessible 5-aminoimidazole-4-carboxamidines. Condensation of these compounds with triethyl orthoformate led to the selective synthesis of the N1-substituted adenines. Regioselective preparation of C6-substituted adenines could be accomplished when the same precursors were combined with dimethylformamide diethyl acetal. These C6-substituted adenines could also be obtained from the N1-substituted adenines by Dimroth rearrangement in the presence of dimethyl amine.     

Asymmetric carbon-carbon bond formations in conjugate additions of lithiated N-Boc allylic and benzylic amines to nitroalkenes: enantioselective synthesis of substituted piperidines,pyrrolidines, and pyrimidinones

(-)-Sparteine mediated lithiations of N-Boc-allylic and benzylic amines provide configurationally stable intermediates which on conjugate additions to nitroalkenes provide highly enantioenriched enecarbamate products in good yields, and with high diastereoselectivities. Straightforward transformations of these adducts offer general routes to substituted 3,4-substituted piperidines, 3,4-substituted pyrrolidines, and 4,5-substituted pyrimidinones. Diastereoselective substitutions of intermediate lactams followed by reduction provide 3,4,5-substituted piperidines and 3,4-trisubstituted pyrrolidines. Lithiation adjacent to nitrogen of 3,4-substituted piperidines and pyrrolidines followed by diastereoselective substitution opens a route to 2,4,5- and 2,4,5,6-substituted piperidines as well as 2,3,4- and 2,3,4,5-substituted pyrrolidines. The enantiomers of the enecarbamate and 3,4-substituted piperidine products may be accessed by stannylation/transmetalation sequences as well as by further manipulation of 4-substituted piperidones. The methodology is used to synthesize both enantiomers of an aspartic peptidase inhibitor intermediate, 3-hydroxy-4-phenylpiperidine, as well as the antidepressant (+)-femoxetine.     

New and practical method for synthesis of 1- and 1,3-substituted xanthines.

[reaction: see text] A new and practical method for the synthesis of 1- and 1,3-substituted xanthines is reported. Direct base-promoted condensation of the imidazole precursor 1 with carbamates 2 gives 1-substituted 7-PMB xanthines 7 in good yields. Alkylation of these derivatives or their potassium salts proceeds under mild conditions to give functionalized 1,3-substituted 7-PMB xanthines 9 in good to excellent yields. The obtained 7-PMB-protected derivatives can be readily deprotected to give the parent 1- and 1,3-substituted xanthines.     

Selenium heterocycles. XXIX. Reaction of substituted 2-thioxo-1,3-thiaselenoles with ethyl diazoacetate,ethyl azidoformate and phenyl azide

Reaction of 5-substituted 2-thioxo-1,3-thiaselenoles with ethyl diazoacetate, phenyl azide and ethyl azidoformate afforded 2-substituted ω-carbethoxy-1,4-thiaselenafulvenes (II) , 5-substituted 2-phenylimino-1,3-thiaselenoles (IV) and 5-substituted 2-carbethoxyimino-1,3-thiaselenoles (V) , respectively. The structure of these compounds were confirmed by spectroscopic methods and chemical analysis.     

The preparation of 4-substituted pyrylium salts and their use in dienal synthesis

The unsubstituted pyrylium nucleus is shown to undergo reaction with cuprate or secondary Grignard organometallic reagents to give intermediate 4-substituted pyrans which are converted into the corresponding 4-substituted pyrylium salts (7 examples) in fair to good overall yield. The synthetic utility of the 4-substituted pyrylium heterocycles is demonstrated by their reaction with organolithium reagents to give 3,5-disubstituted dienals in a highly stereospecific manner (7 examples) via electrocyclic ring opening of the intermediate 2-substituted pyrans.     

Halogen Dance on 2-Iodobenzofuran and 2-Iodobenzothiophene and Related Reactions

When 2-iodobenzofuran was treated sequentially with lithium 2,2,6,6-tetramethylpiperidide in tetrahydrofuran at −50 °C and an aldehyde, the 2-substituted 3-iodobenzofuran resulting from the halogen dance was the only isolated product. However, from 2-iodobenzothiophene, these conditions led to mixtures in which the 2-substituted 3-iodobenzothiophene was always accompanied by the 2-substituted benzothiophene. The use of 2-bromobenzothiophene as a catalyst made it possible to significantly reduce this competitive dehalogenation. To confirm the halogen dance reaction, the products were unambiguously synthesized by using direct halogenations and deprotolithiation-trapping sequences as key steps. Our efforts to access 2,7-disubstituted and 7-substituted derivatives of benzofuran and benzothiophene have also been reported.     

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。     

5-去氮嘌呤核糖核苷类似物的设计与合成研究进展

综述了近年来有关5-去氮嘌呤核糖核苷类似物作为潜在生物活性(如抗病毒、抗肿瘤等)先导化合物的设计与合成研究进展.指出该类先导物的设计与合成主要基于以下两种途径:一是在去氮嘌呤碱基的4-位或5-位引入不同的取代基;二是在去氮嘌呤碱基的4-位或5-位引入不同取代基的同时,对核苷中的糖基进行修饰.并从这两种途径着手介绍了近年来该领域所取得的主要研究进展.     

Efficient kinetic resolution in the asymmetric hydrosilylation of imines of 3-substituted indanones and 4-substituted tetralones

Kinetic resolution of the N-methyl imines of 3-substituted indanones and 4-substituted tetralones could be accomplished by hydrosilylation with a chiral titanocene catalyst. N-Methyl imines of 4-substituted tetralones were resolved to yield, after hydrolysis of the unreacted starting materials, ketones with high ee's and the amine products with high diastereomeric and enantiomeric purity. The utility of this process was demonstrated in the synthesis of sertraline.     

The synthesis and reactions of β-substituted ethyl sulfates

The synthesis of β-substituted ethyl sulfates and their reactions with nucleophilic reagents has been studied. Amines, phenolates, carboxylates, amine oxides, carbanions, and thiophenolates reacted with ethylene sulfate in high yield, with short reaction times, and at low temperatures, to form β-substituted ethyl sulfates. The β-substituted ethyl sulfates were easily hydrolyzed and in some cases were converted into polymeric material.     

新型1,2,3-三唑类化合物的合成及抗菌构效关系

根据活性基团拼接原理, 以4-取代-苯胺为原料, 经重氮化、 关环和缩合反应合成了17个化合物1-(4-取代苯基)-5-取代苯基亚氨基-4-取代-1,2,3-三唑(7a~7c和13a~13d)和1-(4-取代苯基)-5-取代苄基氨基-4-取代-1,2,3-三唑(5a~5c, 10a~10c和14a~14d), 其中化合物5a~5c, 7b, 7c, 10a, 10c, 13b~13d和14b~14c为新化合物, 对所制备化合物的结构进行了表征. 生物活性测试结果表明, 所有化合物均表现出一定的抑菌活性, 对大肠杆菌的抑菌活性均优于氟康唑; 化合物7a和10c对金黄色葡萄球菌的抑制活性明显优于氟康唑; 而化合物13a和13d则对白色念球菌表现出良好的抑制活性, 与三氯生相当.     

Palladium-catalyzed intermolecular coupling of 3-substituted propargylic carbonates with phenols: Synthesis of 2-substituted benzofuran derivatives

We accomplished the synthesis of 2-substituted benzofuran derivatives by the palladium-catalyzed reaction of 3-substituted propargylic carbonates with phenols. The 2-substituted benzofuran derivatives were obtained through the intermolecular coupling of the 3-substituted propargylic carbonates with phenols, and sequential intramolecular cyclization reaction.     

Comparison between non-peripherally and peripherally tetra-substituted zinc (II) phthalocyanines as photosensitizers: Synthesis,spectroscopic, photochemical and photobiological properties

A series of zinc phthalocyanines tetra-α-substituted with 4-(butoxycarbonyl) phenoxy groups (1a) or 4-carboxylphenoxy groups (2a) or 4-(2-carboxyl-ethyl)phenoxy groups (3a), and the corresponding tetra-β-substituted (1–3b) analogues, have been synthesized and characterized. The effects of the position of substituents at the phthalocyanine skeleton on their spectroscopic, photochemical and photobiological properties have been revealed. When compared with the tetra-β-substituted phthalocyanines, the corresponding tetra-α-substituted analogues exhibit a less aggregating trend in the cellular growth medium, a slightly higher singlet oxygen quantum yield and higher photo-stability in DMF, and a comparable cellular uptake. As a result, the tetra-α-substituted zinc phthalocyanines exhibit a higher photocytotoxicity toward MGC803 human gastric carcinoma cells than the tetra-β-substituted counterparts. Among all these compounds, phthalocyanine 2a shows the highest photodynamic activity, which may mainly be due to its non-aggregated nature in cellular culture medium and high cellular uptake.     

Synthesis and some reactions of oxazolidines containing functional groups

A number of hitherto unknown 2-substituted 3-furfuryloxazolidines and 2-substituted 3-tetrahydrofurfuryloxazolidines are synthesized. The reaction of hydroxyethyloxazolidine with esters, and of 5-(phenylaminomethyl)-3-phenyloxazolidine with ethylene chlorohydrin are investigated.     

Heterocyclization of o-(arylethynyl)arylhydrazines as a new procedure for the synthesis of substituted 1H- and 2H-indazoles and indoles

Procedures for the preparation of 3-substituted 1H- and 2H-indazoles and 2-substituted indoles were developed based on cross-coupling of o-iodoarylhydrazines with copper acetylenides in pyridine or dimethylformamide. An alternative procedure for the synthesis of 3-substituted 1H-indazoles involves cyclocondensation of (2-chloroaryl)acetylenes with hydrazine hydrate in butanol.     

Synthesis and some reactions of oxazolidines containing functional groups

A number of hitherto unknown 2-substituted 3-furfuryloxazolidines and 2-substituted 3-tetrahydrofurfuryloxazolidines are synthesized. The reaction of hydroxyethyloxazolidine with esters, and of 5-(phenylaminomethyl)-3-phenyloxazolidine with ethylene chlorohydrin are investigated.     

Palladium-catalyzed reaction of o-alkynyltrifluoroacetanilides with 1-bromoalkynes. An approach to 2-substituted 3-alkynylindoles and 2-substituted 3-acylindoles

The palladium-catalyzed reaction of o-alkynyltrifluoroacetanilides with 1-bromoalkynes affords free N-H 2-substituted 3-alkynylindoles in satisfactory to high yield. 2-Substituted 3-alkynylindoles revealed useful intermediates for the regioselective synthesis of 2-substituted 3-acylindoles. The latter can be prepared from o-alkynyltrifluoroacetanilides and 1-bromoalkynes via a one-pot cyclization-hydration protocol, omitting the isolation of 2-substituted 3-alkynylindoles.     

A Theoretical Study on the Tautomerism of C-Carboxylic and Methoxycarbonyl Substituted Azoles

DFT calculations (B3LYP/6-31+G^**) have been carried out on 106 tautomers and conformers of NH-azoles bearing CO₂H and CO₂CH₃ groups. The following azoles systems have been studied: 2-substituted pyrroles, 2-substituted indoles, 2-substituted imidazoles, 2-substituted benzimidazoles, 4(5)-substituted imidazoles, 3(5)-substituted pyrazoles, 3-substituted indazoles (1H and 2H), 3,4(5)-substituted-1,2,3(5)-triazoles, 2,3(5)-substituted-1,2(3),4-triazoles, 4(5)-1,2,3,4(5)-tetrazoles. In the case of pyrazole, 3,5-disubstituted derivatives have also been computed, including four dimers.Dedicated to our friend Professor Vladimir I. Minkin on his 70th anniversary.     

Synthesis and spectral data of pyrido[2,3-e]-as-triazines

The pyrido[2,3-e]-as-triazine and its 3-phenyl derivatives were prepared via cyclisation with polyphosphoric acid of suitable 3-substituted 2-aminopyridines obtained by reduction of the corresponding 2-nitropyridines. The 3-substituted 2-nitropyridines were obtained by action of hydrazine or benzoylhydrazide with the appropriate 3-halo-2-nitropyridines; only 3-fluoro-2-nitropyridine leads to the 3-substituted 2-nitropyridines. This experimental results are in agreements with the CNDO and MNDO calculations.     

A flexible method for the synthesis of 2-substituted 1,2,5,6-tetrahydropyridines and piperidines from chloro-containing propargylamines

A general approach for the stereoselective synthesis of 2-substituted 1,2,5,6-tetrahydropyridines and piperidines is described. The addition of 4-chloro-1-butyne to Ellman sulfinimines to produce chloro-containing propargylamines, reduction with Lindlar catalyst, and cyclization using LHMDS provides efficient, stereoselective access to diverse 2-substituted 1,2,5,6-tetrahydropyridines. For substrates incompatible with the LHMDS cyclization reaction conditions removal of the sulfinamide moiety and cyclization with Cs₂CO₃ allows the preparation of the corresponding 2-substituted 1,2,5,6-tetrahydropyridines. This method can be extended to the synthesis of 2-substituted piperidines through reduction of the chloro-containing propargylamine with PtO₂.