Synthesis and Biological Activities of Arylspiroborates Derived from 2,3‐Dihydroxynaphthalene

A family of arylspiroborate compounds has been prepared from 2,3‐dihydroxynaphthalene and characterized fully using multinuclear NMR spectroscopy and elemental analyses. Single crystal X‐ray diffraction studies were carried out on the tetramethylammonium ( 4 ) and calcium ( 6 ) derivatives. Compound 6 represents the first structurally characterized example of a calcium arylspiroborate salt. All compounds showed modest antifungal and antimycobacterial activities. These results have revealed a new class of compounds that should be further developed to design more potent and selective antitubercular agents. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:116–123, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21072     

微波促进的非环核苷类化合物的合成

以嘌呤碱基和各种α,β-不饱和醛为原料,用三乙胺作为催化剂,在微波的促进下,通过Michael加成反应和原位还原,高效地合成了一系列非环核苷类新化合物.得到的目标化合物通过核磁共振图谱、高分辨质谱进行了确认.     

Efficient Synthesis and Antimicrobial Evaluation of Acyclic Pyrimidine Nucleosides and Their Sulfanyl Analogs

Russian Journal of Organic Chemistry - A facile synthetic approach has been proposed for a new series of uracil acyclic nucleosides and their sulfanyl analogs via reaction of pyrimidine derivatives...     

Synthesis and Biological Activity of 2′-Fluoro-D-arabinofuranosylpyrazolo[3,4-d]pyrimidine Nucleosides

Coupling of 2-fluoro-3,5-di-O-benzoyl-α-D -arabinofuranosyl bromide with 4-methoxypyrazolo[3,4-d]pyrimidine gave an α-D /β-D mixture of N¹- and N²-coupled products. All the anomers were separated and deblocked to yield the corresponding nucleosides. The β-D -anomer 7 was converted to the 4-amino derivative 11 , which was deaminated by adenosine deaminase to give the 4-oxo compound 12 . Compound 7 showed significant activity against human cytomegalovirus and hepatitis B virus, and compound 11 showed activity against human herpes virus 8. All the compounds were noncytotoxic in several human tumor-cell lines in culture.     

Synthesis and Evaluation of Four Hederagenin Glycosides as α‐Glucosidase Inhibitor

The four hederagenin glycosides 1 – 4 were efficiently synthesized through one‐pot sequential glycosylations with glycose 1‐(trichloroacetimidate)s as donors, resulting in a significantly simplified synthetic procedure without isolation of glycosylation intermediates. The activity of the synthetic hederagenin glycosides 1 – 4 against α‐glucosidase type IV was evaluated; hederagenin glycoside 4 containing an α‐L ‐rhamnopyranosyl unit showed the best activity with an IC₅₀ value of 47.9 μM .     

Synthesis of (2′S)‐2′‐Deoxy‐2′‐C‐methylpurine Nucleosides and Their Phosphoramidites

We describe the stereoselective synthesis of (2′S)‐2′‐deoxy‐2′‐C‐methyladenosine ( 12 ) and (2′S)‐2′‐deoxy‐2′‐C‐methylinosine ( 14 ) as well as their corresponding cyanoethyl phosphoramidites 16 and 19 from 6‐O‐(2,6‐dichlorophenyl)inosine as starting material. The methyl group at the 2′‐position was introduced via a Wittig reaction (→ 3 , Scheme 1) followed by a stereoselective oxidation with OsO₄ (→ 4 , Scheme 2). The primary‐alcohol moiety of 4 was tosylated (→ 5 ) and regioselectively reduced with NaBH₄ (→ 6 ). Subsequent reduction of the 2′‐alcohol moiety with Bu₃SnH yielded stereoselectively the corresponding (2′S)‐2′‐deoxy‐2′‐C‐methylnucleoside (→ 8a ).     

Synthesis and Conformational Analysis of 1′‐ and 3′‐Substituted 2‐Deoxy‐2‐fluoro‐D‐ribofuranosyl Nucleosides

Convergent syntheses of the 9‐(3‐X‐2,3‐dideoxy‐2‐fluoro‐β‐D ‐ribofuranosyl)adenines 5 (X=N₃) and 7 (X=NH₂), as well as of their respective α‐anomers 6 and 8 , are described, using methyl 2‐azido‐5‐O‐benzoyl‐2,3‐dideoxy‐2‐fluoro‐β‐D ‐ribofuranoside ( 4 ) as glycosylating agent. Methyl 5‐O‐benzoyl‐2,3‐dideoxy‐2,3‐difluoro‐β‐D ‐ribofuranoside ( 12 ) was prepared starting from two precursors, and coupled with silylated N⁶‐benzoyladenine to afford, after deprotection, 2′,3′‐dideoxy‐2′,3′‐difluoroadenosine ( 13 ). Condensation of 1‐O‐acetyl‐3,5‐di‐O‐benzoyl‐2‐deoxy‐2‐fluoro‐β‐D ‐ribofuranose ( 14 ) with silylated N²‐palmitoylguanine gave, after chromatographic separation and deacylation, the N⁷‐β‐anomer 17 as the main product, along with 2′‐deoxy‐2′‐fluoroguanosine ( 15 ) and its N⁹‐α‐anomer 16 in a ratio of ca. 42 : 24 : 10. An in‐depth conformational analysis of a number of 2,3‐dideoxy‐2‐fluoro‐3‐X‐D ‐ribofuranosides (X=F, N₃, NH₂, H) as well as of purine and pyrimidine 2‐deoxy‐2‐fluoro‐D ‐ribofuranosyl nucleosides was performed using the PSEUROT (version 6.3) software in combination with NMR studies.     

Synthesis and Biological Evaluation of Novel 2‐Aryl Benzimidazoles as Chemotherapeutic Agents

Here, we describe the synthesis and preliminary biological evaluation of novel N‐unsubstituted and N‐methylated 2‐aryl benzimidazole derivatives that contain fluorinated or hydroxylated alkyl substituents in the 4‐N‐aryl position and different substitution patterns (H vs Br vs I) in the benzimidazole ring. For the selected compounds and for comparison purposes, the congener benzothiazoles were also tested. The cytotoxic effect of 11 benzazole derivatives was evaluated in a panel of human cancer cell lines, such as breast (MCF7), melanoma (A375), cervix (HeLa), and glioblastoma (U87). In general, the compounds exerted a moderate cytotoxic activity against all cells tested. In particular, for the A375 and HeLa cells, the N‐unsubstituted benzimidazoles 2 and 3 displayed a better cytotoxic profile than the respective N‐methylated benzimidazole congeners ( 5 and 7 ). The biodistribution of compound 2 , which has shown the highest cytotoxic activity active in the U87 glioblastoma cells (IC₅₀ = 45.2 ± 13.0), was evaluated in CD1 mice using its ¹⁸F‐labeled counterpart ( [¹⁸F]2 ). These studies showed that compound 2 can cross the blood brain barrier with a reasonable brain uptake (1.24 and 2.81%I.A./g at 5 and 60 min p.i., respectively), which is a crucial issue for systemic chemotherapy of glioblastoma. Altogether, the in vitro antitumoral activity of benzimidazole 2 against the U87 cells and the ability of its ¹⁸F‐congener to cross the blood brain barrier provide a strong rationale to consider the reported fluoroalkylated 2‐aryl benzimidazoles as lead candidates for the generation of chemotherapeutic agents, in particular, against highly aggressive brain tumors such as glioblastoma.     

New Acyclic 12‐Hydroxygeranylgeraniol‐Derived Diterpenoids from the Seeds of Carpesium triste

Five new acyclic 12‐hydroxygeranylgeraniol‐derived diterpenoids, i.e., 1 – 5 , were isolated from the seeds of Carpesium triste. The structures including the absolute configurations of the new compounds were elucidated by spectroscopic methods. All the compounds, except for 2 , were evaluated for their in vitro cytotoxic activity against cultured SMMC‐7721 (human hepatoma), HL‐60 (human promyelocytic leukemia), and L02 (human hepatocyte) cells.     

Synthesis and Biological Activity of a Series of Novel N‐Substituted β‐Lactams Derived from Natural Gallic Acid

A series of novel β‐lactams derived from natural gallic acid were conveniently synthesized via classical Staudinger ketene‐imine cycloaddition reaction. Their structures were confirmed by satisfactory analytical and spectroscopic methods. The preliminary bioassay showed that some of the target compounds exhibited obvious insecticidal activity against Heliothis armigera at the dosage of 0.2 mg/mL.     

Synthesis and Biological Evaluation of New Ibuprofen‐1,3,4‐oxadiazole‐1,2,3‐triazole Hybrids

A new hybrid polydentate template comprising distinctive pharmacophoric groups, namely, ibuprofen, 1,3,4‐oxadiazole, and 1,2,3‐triazole linked through a thioether bridge was achieved by one‐pot synthesis by exploring multicomponent Cu‐catalyzed “click chemistry” approach. The target structures were characterized by NMR, IR, and LC‐Mass. The X‐ray analysis of 2‐(1‐(4‐isobutylphenyl)ethyl)‐5‐(((1‐(3‐nitrophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐1,3,4‐oxadiazole ( 8a ) confirmed the assigned structure. The in vitro antibacterial and anticancer activity of these compounds revealed that 2‐(1‐(4‐isobutylphenyl)ethyl)‐5‐(((1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐1,3,4‐oxadiazole ( 8b ) demonstrated more potent antibacterial activity against Gram‐negative strains (Escherichia coli and Pseudomonas aeruginosa) and 2‐(((1‐(2,4‐dimethylphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐5‐(1‐(4 isobutylphenyl)ethyl)‐1,3,4‐oxadiazole ( 8e ) exhibited anticancer activity with IC₅₀ of 27.50 and 31.03 μg/mL against HeLa and MCF‐7 cell lines, respectively.     

Nucleosides XIII. Facile Synthesis of 4‐Amino‐1‐(2‐deoxy‐β‐D‐ribofuranosyl)quinazolin‐2‐one as a 2′‐Deoxycytidine Analog for Oligonucleotide Synthesis

4‐Amino‐1‐(2‐deoxy‐β‐D‐ribofuranosyl)quinazolin‐2‐one (4) was prepared by Barton deoxygenation from 4‐amino‐1‐(β‐D‐ribofuranosyl)quinazolin‐2‐one (3) as a 2′‐deoxycytidine analog.     

Synthesis,Antiplatelet Aggregation Activity Evaluation and 3D‐QSAR of a Series of Novel 6‐Alkylamino(Alkoxyl)‐2‐Propylthio‐8‐Azapurine Nucleosides

A series of novel 6‐alkylamino(alkoxyl)‐2‐propylthio‐8‐azapurine nucleosides were synthesized by an improved route, and the human antiplatelet aggregation activities of these new compounds were evaluated. A self‐organizing molecular field analysis method was used to study the three‐dimensional quantitative structure–activity relationship of these novel nucleosides. The results of the antiplatelet aggregation activity evaluation and analysis of the self‐organizing molecular field analysis models through shape and electrostatic grids may provide a basis for the development of new and potent antiplatelet agents.     

Design,Synthesis, and Biological Evaluation of 3,5‐Disubstituted 2‐Pyrazineamide Derivatives as Antitubercular Agents

A novel series of 3,5‐disubstituted‐2‐pyrazineamide derivatives ( 5a–5o ) were synthesized and studied for their potential as antitubercular agents. Among them, the compounds 5a , 5g , and 5m showed the good minimal inhibitory concentration of 20, 25, and 25 μg/mL, respectively. The compound 5a displayed excellent minimum inhibitory concentration of 10 μg/mL and is four times more potent compared with the standard drug, rifampicin concentration. In silico docking studies revealed that the compounds 5a and 5c can bind strongly in the active site of 2FUM enzyme and prevent enzyme–substrate interactions. In addition, in silico docking studies were calculated, and based on the data obtained, compound 5a displayed excellent drug‐like properties.     

New Heterocyclic Compounds Derived from 4,6‐Diamino‐3‐cyano‐2‐methylthiopyridine and their Biological Activity

Treatment of 4,6‐diamino‐3‐cyano‐2‐methylthiopyridine ( 1 ) with aqueous KOH or hydrazine hydrate afforded the corresponding nicotinamide 2 and pyrazolo[3,4‐b]pyridine 3 , respectively. Reaction of compound 1 with bromine, sulfuryl chloride, formaldehyde, or aromatic diazonium salts gave 5‐bromopyridine 4 , 5‐chloropyridine 5 , dipyridylmethane 6 , and azo dyes 7 , 8 , 9 , 10 , respectively. Compound 1 reacted with diketones to yield the corresponding butenylamino derivative 11 and amides 12 , 13 , 14 , 15 , respectively. Treatment of butanamide 13 with diazonium salts or a mixture of urea and aromatic aldehyde in the presence of drops of HCl as a catalyst yielded the corresponding arylhydrazones 16 , 17 , 18 , 19 , pyrimidines 20 , 21 , 22 , 23 , 24 , and 1,8‐naphthyridine 25 , respectively. The potency of the results as anti‐inflammatory and antifungal agents have been evaluated. The compounds have been characterized based on their spectral and elemental analysis.