Ge Meng

Design and synthesis of a new series of modified CH-diarylpyrimidines as drug-resistant HIV non-nucleoside reverse transcriptase inhibitors

This article reports the design, synthesis and antiviral evaluation of a new series of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The basic skeleton of these target 18 molecules is diarylpyrimidine featuring a substituted amino group between the pyrimidine scaffold and the aryl wing. All of the new compounds have been characterized by spectra analysis. The entire target molecules were evaluated for their in vitro anti-HIV activity with controlling group of FDA approved drugs. Most of them showed good to potent activities against wild-type (WT) HIV-1 with IC50 values in the range of 0.0175-69.21 μM. 2-(4-Cyanophenylamino)-4-(2-cyanovinylphenylhydrazonomethyl)pyrimidine (1d) displayed potent anti-HIV-1 activity against WT HIV-1 with a selectivity index (SI) of 106367 and an IC50 value of 1.75 nM, which was 47 fold lower than that of AZT. Compound 1d also showed a broad-spectrum inhibitory activity, with an IC50 value of 5.33 μM and 5.05 μM against both HIV-1 double-mutated (K103N/Y181C) strain and HIV-2 strain, respectively. The preliminary structure-activity relationship (SAR) was also investigated. The binding modes with HIV-1 RT for both the wild type and mutant type have also been discussed.

Efficient and eco-friendly preparation of 4-methyl-5-formyl-thiazole.

4-Methyl-5-formylthiazole, an intermediate for synthesizing cefditoren pivoxil, was prepared in good yield by Pd/BaSO4 catalyzed hydrogenation of 4-methylthiazole-5-carboxylic acid chloride. Detailed reaction conditions have been studied.

Zinc ion mediated synthesis of cuprous oxide crystals for non-enzymatic glucose detection

Morphology control is expected to be an effective method to enhance the electrochemical properties of materials. In this work, zinc cation-mediated growth of Cu2O crystals was achieved via an aqueous chemical route at room temperature. Thus, by simply increasing the concentration of Zn2+, concave cube-like (C-Cu2O), porous (P-Cu2O), and hierarchical (H-Cu2O) Cu2O crystals were selectively obtained. The morphologies and structures of the as-prepared Cu2O crystals were characterized by SEM, TEM, XRD and XPS. The three materials were subsequently employed as active materials for the non-enzymatic detection of glucose. The H-Cu2O-based electrode exhibited the highest sensitivity (3076 μA mM-1 cm-2) in virtue of its highest surface area, while the P-Cu2O-based electrode showed the widest linear range (up to 24 mM). The reliability of the Cu2O-based glucose sensors was proved by determining their detection limit, response time, selectivity, and stability characteristics on human serum samples. This work provides a novel strategy for the morphology-controlled Zn2+-mediated fabrication of Cu2O crystals with different glucose sensing performances depending on their structures.

Design and synthesis of a new series of cyclopropylamino-linking diarylpyrimidines as HIV non-nucleoside reverse transcriptase inhibitors

A new series of 29 diarylpyrimidine analogues featuring a cyclopropylamino group between the pyrimidine scaffold and the aryl wing have been synthesized. All of the new compounds have been characterized by spectra analysis. The target molecules were evaluated for their in vitro anti-HIV activity with FDA-approved drugs as references. Some of the compounds exhibited moderate to potent activities against wild-type HIV-1. The compound 4-((4-((cyclopropylamino)(2,5-difluorophenyl)methyl)pyrimidin-2-yl)amino)benzonitrile (1e) displayed potent anti-HIV-1 activity against WT HIV-1 with an IC50 of 0.099 μM and a selectivity index of 2302. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated.

Improved Preparation of 2,4-Thiazolidinedione

The widely utilized industrial product 2,4-thiazolidinedione (3) has been chosen as the starting material for our ongoing research on rosiglitazone,1 which is a selective PPAR-γ receptor inhibitor for the treatment of type-II diabetes.2 Based on the literature3 and our own experience, we developed an efficient one-step method to obtain 3 using conc. hydrochloric acid.4 This improved synthesis seemed to be much better than the previous methods,3 all of which shared the disadvantage that the strongly acidic waste from the reaction and solvents from the recrystallization process have to be disposed of without harm to the environment. In order to alleviate these problems, we decreased the amount of hydrochloric acid and our results show that the yield of 3 is still acceptable while the concentration of HCl has been decreased by more than one half (Table 1). This result encouraged us to do further research,5 which resulted in a green and inexpensive method to prepare 3. Herein, we report this economic and environmentally friendly synthesis of 3, starting from chloroacetic acid (1) and thiourea (2) using water as the solvent for the preparation as well as the recrystallization process.

Efficient one-pot synthesis of ethyl 2-substitued-4-methylthiazole-5-carboxylates

A new and practical one-pot procedure for the synthesis of several 2-sustituted-4-methylthiazole-5-carboxylates from commercially available starting materials is described. Under mild reaction conditions, some of the products with alkyl group on the 2-amino group or with various groups on 2-substituted phenyl ring were obtained in good yields from ethyl acetoacetate, N-bromosuccinimide, thiourea, or its N-substituted derivatives in an efficient way instead of the traditional two-step reaction.

An Eco-friendly Preparation of 2-Iminothiazolidin-4-ones Derivatives

Functionalized 2-thiazolidin-4-ones are important heterocyclic compounds owing to their biological activities,1,2 such as anti-tuberculosis,3 anti-convulsant,4 fungistatic,5 bacteriostatic,6 antimicrobial,7 antiviral,8 anti-cancer,9 and immunomodulation properties.10 2-Iminothiazolidin-4-one (3a) and 3-ethyl-2-(ethylimino)thiazolidin-4-one (3b) are two important basic structures in this category. The active methylene group (CH2) at the 5-position of 3 might provide opportunities for structure modifications, viz. via Knoevenagel condensation with various aldehydes to give 5-substituted derivatives. Compounds 3 have thus been used as important intermediates for synthesis of many biologically active compounds, such as rosiglatazone,11 picoglatazone,12 etc. Conventional synthesis of 2-iminothiazolidin-4-ones (3) involved cyclization from thioureas with chloroacetic acid derivatives via using various catalysts,13,14 which include mineral acid15 and organic or inorganic bases such as sodium acetate,6,16–18 sodium hydride,10 triethylamine,9 and pyridine.10 Chloroacetic acid may be replaced by its esters,19 acid chloride,9,10 acylamides10,20 or 2-mecaptoacetic acid.21 All these methods share shortcomings and are not suitable for large-scale green manufacture.22 In order to solve this problem, we have developed an environmentally friendly method to synthesize 3 based on our experiences.15 Chloroacetic acid ionizes in water into protons which catalyze the reaction, thus making it a self-catalyzed reaction. The improved simple procedure involves heating the thioureas and chloroacetic acid in water and recrystallizing the products from water. The process offers an eco-friendly preparing of 3 for industrial purposes (Scheme 1).

An Improved Two-step Preparation of 2,4-Dimethylpyrrole

2,4-Dimethylpyrrole (1) is a very important intermediate in the synthesis of fluorescent molecules (such as BODIPY),1,2 the new tyrosine kinase inhibitor (such as sunitinib),3–5 anti-inflammatory/analgesic agent6 and so forth. The traditional synthetic methods of 1 usually involved several steps including the construction of the pyrroles skeleton by the Knorr reaction using 1,3-diketones,7 and by oximation of either acetoacetic esters or malonates via a dissolving-zinc reduction and subsequent hydrolysis, acidification and decarboxylation (Scheme 1).8,9

Synthesis of 1‐[(2‐Hydroxyethoxy)Methyl]‐6‐(5,6,7,8‐Tetrahydronaphthylmethyl‐1)Thymine as Novel Inhibitor against Drug‐Resistant HIV Mutants

Abstract Synthesis of two new 1‐[(2‐hydroxyethoxy)methyl]‐6‐(5,6,7,8‐tetrahydronaphthylmethyl‐1)thymine derivatives 10a–b, as potent inhibitors against a mutant type of HIV, starting from thymine, is described. In the preparation of the corresponding 10a–b from compounds 9a–b, the three‐step reaction via deprotection, hydrogenolysis, and hydrogenation was carried out in a one‐pot procedure.

A PRACTICAL SYNTHESIS OF (3aα, 6aα)-1,3-DIBENZYL HEXAHYDRO-1H-THIENO[3,4-d]IMIDAZOL-2(3H)-ONE

During the course of our investigation on the synthesis of d-biotin, which is utilized as a nutritional supplement for humans and animals,’.? (3aa, 6aa)1,3-dibenzylhexahydro1 H-thieno[3,4dJimidazol-2(3H)-one (4) was required as a key intermediate, which had previously been prepared by Lavielle et af.’ In our hand, however, this procedure resulted in little product (ca. 5% overall yield). Herein we present a modified, simple method for the synthesis of 4 with an overall yield of 77% from the known 1,3-dibenzyl-2-imidazolidone-4,5-cis-dicarboxylic acid ( 1)4 as shown in the scheme. Selective reduction of 1 with Zn(BH,), generated in sihi by reaction of KBH, with ZnCI,, in anhydrous THF at reflux for 10 h afforded cleanly the corresponding diol 2 in 92% yield. Since the mesylate of 2 used in Lavielle’s procedure was poorly soluble in EtOH, it was decided to use the dichloride 3. However, attempted chlorination of the hydroxyl groups in 3 with SOCl,, PCI,, POCl, was unsuccessful. The corresponding dichloride 3 was ultimately obtained in 9 I % yield using Vilsmeier reagent (chloromethylenedimethylammonium chloride), which was conveniently prepared by reaction of PCl, with anhydrous DMF.’ Treatment of 3 with Na,S*9H,O in a diphase system (CHCI,-H,O) with a catalytic amount of triethylbenzylammonium chloride (TEBAC) as a phasetransfer catalyst at reflux for 6h afforded the desired 4 as white crystals in 92% yield. It is worth mentioning that the reaction time was longer (14 h) and the yield of 4 decreased to 64% when no phase-transfer catalyst was employed.