Synthesis and biological evaluation of novel C6-amino substituted 4-azasteroidal purine nucleoside analogues.

Novel C6-amino substituted purine nucleoside analogues (2-12) bearing a modified pyranose-like D ring of the 4-azasteroid moiety were efficiently synthesized through nucleophilic substitution at C6 position of the steroidal nucleoside precursors (1a, b) with versatile amines. All the synthesized new compounds were evaluated for their anticancer activity in vitro against Hela, PC-3 and MCF-7 cell lines. Among them, compounds 4b, 7b and 9b exhibited significant cytotoxicity with the IC50 values of 2.99 µM (PC-3), 2.84 µM, (PC-3) and 2.69 µM (Hela), respectively.

Synthesis and biological evaluation of novel steroidal[17,16-d][1,2,4]triazolo[1,5-a]pyrimidines.

The preparation of steroidal[17,16-d][1,2,4]triazolo[1,5-a]pyrimidines and their biological evaluation as potential anticancer agents are herein reported. These novel heterosteroids (2, 4) were prepared through the condensation reaction of 3-amino-1,2,4-triazole with 16-arylidene-17-ketosteroids (1, 3). All the synthesized compounds were evaluated for their anticancer activity in vitro against PC-3 (human prostatic carcinoma), MCF-7 (human breast carcinoma) and EC9706 (human esophageal carcinoma) cell lines. Among the screened compounds, 2i, 2n and 4f showed significant inhibitory activity against all the three human cell lines.

Synthesis of novel D-ring fused 7'-aryl-androstano[17,16-d][1,2,4] triazolo[1,5-a]pyrimidines.

The preparation of novel steroidal heterocycles containing the 7-aryl-substituted 1,2,4-triazolo[1,5-a]pyrimidine moiety fused to the 16,17-positions of the steroid nucleus is described. The Aldol reaction of 4-aza-androst-3,17-dione (1a) and dehydroepiandrosterone (DHEA, 1b) with aromatic aldehydes was catalyzed by KF/Al(2)O(3) to give the corresponding 3-oxo-4-aza-5α- and 3ß-hydroxy-5-en-16-arylidene-17-ketosteroids (2a-r). Subsequently, the intermediates 2a-r reacted with dinucleophilic 3-amino-1,2,4-triazole in presence of t-BuOK to afford the title compounds (3a-r). All the synthesized heterosteroids are new and are currently being evaluated for their biological activities.

Novel 4-azasteroidal N-glycoside analogues bearing sugar-like D ring: synthesis and anticancer activities.

A series of novel N-glycoside analogues with 4-azasteroid moiety bearing sugar-like D ring were conveniently synthesized by constructing the core dihydropyran ring embedded in 4-azasteroidal skeleton which was prepared from 4-aza-5α-androst-3,17-dione 1 in four steps. The structure of 6b were unambiguously proved by the appropriate X-ray structural analysis. Anticancer activity was found for all of the analogues with purinyl moiety against breast cancer (MCF-7), human neuroblastoma (SK-N-SH), cervical cancer cell (HeLa) and prostatic cancer (PC-3), while the analogue 7 containing 1,2,4-triazole heterocycle as the nucleobase was inactive against all of the tested cancer cell lines. The biology results showed the purinyl moiety attached to the pyran ring of 6a-d, substituent at 6'-position of purine base and introduction of a halogen atom at 2'-position of 6'-chloropurine had obviously effect on the evaluated anticancer activity.

From one to three: a serine derivate manipulated homochiral metal-organic framework.

A porous homochiral MOF was constructed from a serine derivate ligand bridged and chelated copper atom subunit, which can expand one chiral center into multitopic homochiral centers to systematically tune the heterogeneous catalytic properties.

A cascade approach to pyridines from 2-azido-2,4-dienoates and alpha-diazocarbonyl compounds.

A one-pot synthesis of substituted pyridines via a cascade reaction of 2-azido-2,4-dienoates with alpha-diazocarbonyl compounds and triphenylphosphine is reported. The process involves a Staudinger-Meyer reaction, a Wolff rearrangement, an aza-Wittig reaction, and an electrocyclic ring-closure. The procedure is general and efficient. The substrates are readily available.

Synthesis of indoles via domino reaction of N-aryl amides and ethyl diazoacetate.

A general and concise synthesis of functionalized indoles via domino reaction of N-aryl amides and ethyl diazoacetate has been developed. The methodology offers a great potential for the synthesis of biologically active and naturally occurring indole derivatives.

A tandem approach to isoquinolines from 2-azido-3-arylacrylates and alpha-diazocarbonyl compounds.

2-Azido-3-arylacrylates react with alpha-diazocarbonyl compounds and triphenylphosphine to furnish isoquinolines in 60-92% yields. The tandem process involves a Wolff rearrangement, an aza-Wittig reaction, and an electrocyclic ring closure. The procedure is efficient, rapid, and general, and the substrates are readily available.

Selective synthesis of 4-alkylidene-beta-lactams and N,N'-diarylamidines from azides and aryloxyacetyl chlorides via a ketenimine-participating one-pot cascade process.

A one-pot cascade approach to 4-alkylidene-beta-lactams and N, N'-diarylamidines from aryl azides and aryloxyacetyl chlorides has been developed. The chemical outcome of the reaction can be controlled selectively by an appropriate choice of the stoichiometric ratio of different substrates and reagents. The products should find use in pharmaceutical discovery, especially in the development of new antimicrobial agents against multidrug-resistant pathogens.

Copper-catalyzed multicomponent reaction: facile access to novel phosphorus amidines.

The synthesis of a novel class of phosphorus amidines via a copper-catalyzed multicomponent reaction of sulfonyl azides, alkynes and iminophosphoranes is described. The protocol is efficient and general.

Facile access to pyrazolines via domino reaction of the Huisgen zwitterions with aziridines.

A novel, efficient, and general domino reaction of 2-acylaziridines with the Huisgen zwitterions to furnish 2-pyrazoline rings is described. A possible mechanism for the domino sequence is proposed.

Copper-catalyzed multicomponent reaction: facile access to functionalized 5-arylidene-2-imino-3-pyrrolines.

The synthesis of a novel class of 2-imino-5-arylidene-3-pyrrolines via a copper-catalyzed multicomponent reaction of sulfonyl azides with alkynes and aziridines is described. The protocol is efficient and general.

Domino reaction of 3-(2-formylphenoxy)propenoates and amines: a novel synthesis of 1,4-dihydropyridines from salicaldehydes, ethyl propiolate, and amines.

A novel synthesis of Hantzsch-type N-substituted 1,4-dihydropyridines from salicaldehydes, ethyl propiolate, and amines has been developed. Salicaldehydes were treated with ethyl propiolate in the presence of N-methylmorpholine to give ethyl 3-(2-formylphenoxy)propenoates. Three equivalents of ethyl 3-(2-formylphenoxy)propenoates reacted with 1 equiv of amines under trifluoroacetic acid (TFA) catalyst to furnish the corresponding N-substituted 1,4-dihydropyridines in good to excellent yields, recovering the starting material salicaldehydes. A possible mechanism for the domino process was proposed. Furthermore, the products can be easily derived via further transformations and three of them exhibited strong fluorescence (Phif = 0.36-0.63).

Cascade approach to substituted 6-aryl-phenanthridines from aromatic aldehydes, anilines, and benzenediazonium-2-carboxylate.

Aromatic aldehydes reacted with anilines and benzenediazonium-2-carboxylate to afford 6-aryl-phenanthridines. The reaction furnishes a rapid and direct construction of substituted phenanthridine rings from readily available starting materials via a one-pot cascade process.

Synthesis of a benzyl-protected analog of arenarioside, a trisaccharide phenylpropanoid glycoside.

A benzyl-protected analog of the phenylpropanoid glycoside arenarioside, (4-benzyloxyphenyl)ethyl alpha-L-rhamnopyranosyl-(1-->3)-4-O-[(E)-3,4-di-O-benzyl-caffeoyl]-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranoside (22), was synthesized through two different routes from D-glucose. This is the first approach on the synthesis of a trisaccharide phenylpropanoid glycoside, although the benzyl-protecting group in the backbone of the arenarioside analog could not be removed by conventional debenzylation procedures.

Novel and efficient synthesis of iminocoumarins via copper-catalyzed multicomponent reaction.

A variety of substituted iminocoumarins are prepared in good to excellent yields via a copper-catalyzed multicomponenet reaction of sulfonyl azides, terminal alkynes, and salicylaldehydes or o-hydroxylacetophenones. The method is general, mild, versatile, and efficient. A plausible mechanism for the domino process is proposed.

A highly selective cascade approach to diverse aromatic ring systems from simple aromatic aldehydes and propiolates.

[reaction: see text] A new triethylamine-catalyzed cascade reaction of aromatic aldehydes with propiolates has been developed. This serial multi-bond-forming process furnishes diverse polycyclic aromatic hydrocarbons, including naphthalenes, phenanthrenes, benzofurans, and 2,3,9,9a-tetrahydronaphtha[2,3-b]furans. The chemical outcome of the process depends on the reaction temperature and can be tailored selectively by an appropriate choice of experimental conditions.

Parallel synthesis of strongly fluorescent polysubstituted 2,6-dicyanoanilines via microwave-promoted multicomponent reaction.

[reaction: see text] A facile parallel synthesis of polysubstituted 2,6-dicyanoanilines via microwave-promoted three-component reaction of aldehydes, ketones, and propanedinitrile in solution and also on polymer support has been developed. The screening for optical properties identified two new compounds with high fluorescence quantum yields.

Microwave-assisted amination from aryl triflates without base and catalyst.

[reaction: see text] Aryl triflates are effectively converted to the corresponding anilines under microwave irradiation in 1-methyl-2-pyridone (NMP) without base and catalyst. Aryl triflates substituted with both electron-poor and electron-rich groups give good to excellent yields. It is noteworthy that the halogenated aryl triflates can chemoselectively react with amines to afford halogenated anilines.

Design, synthesis and antitumor activities of novel 7-arylseleno-7-deoxydaunomycinone derivatives.

7-Arylseleno-7-deoxydaunomycinone derivatives 3a-e and 7-thiophenyl-7-deoxydaunomycinones (7 and 8) were synthesized and the antitumor activities of them were evaluated against human stomach cancer SGC-7901 and human leukaemia HL60. The cytotoxic assay show that seleno daunomycinone derivatives are much better inhibitory activity than thiodaunomycinone and the structure-activity relationship was discussed. 7-Deoxydaunomycinone 4 was obtained when selenophenols were used in excess and the possible mechanism was proposed.