Tieming Cheng

Novel bioactive isoquinoline alkaloids from Carduus crispus

Four novel isoquinoline alkaloids crispine B–E (2–5), along with a new natural isoquinoline alkaloid, crispine A (1), were isolated from Carduus crispus, and the structures were elucidated on the basis of spectroscopic data. Crispine A and B are alkaloids with pyrrolo-[2,1-a]isoquinoline skeleton and crispine C–E are isoquinoline alkaloids with guanidinyl group. All compounds were evaluated for their cytotoxic activity ad compound 2 showed certain cytotoxic activity against some human-cancer lines in vitro.

Design, synthesis and biological evaluation of tripeptide boronic acid proteasome inhibitors

A series of tripeptide boronate proteasome inhibitors were designed and synthesized on the basis of our previously built tripeptide aldehyde 3D-QSAR models. All the synthesized compounds were evaluated for their proteasome-inhibitory activities in an isolated 20S rabbit proteasome, and selected compounds were evaluated for their antitumor activities in vitro against four human cancer cell lines. Biological results showed bulky and negative substituents at P(2) position improved the proteasome-inhibitory potency obviously, which completely conformed to the theoretical models, while those at P(3) position thoroughly deviated from the 3D-QSAR model. Most of the screened compounds showed less than 1 nM inhibitory potency and high selectivity against 20S proteasome, of which 7f is the most potent (IC(50)=0.079 nM) and twofold more active than bortezomib (IC(50)=0.161 nM). Cell viability indicated hydrophilic 4-hydroxyphenyl substituent at P(2) or P(3) position was not favorable to the cellular activities. Especially for the two hematologic cancer cell lines, HL-60 and U266, 7f inhibited them at the level of less than 10 nM and was more potent than the control bortezomib. It is being considered a promising new lead to be developed for the treatment of various cancers.

Y(OTf)3-catalyzed novel Mannich reaction of N-alkoxycarbonylpyrroles, formaldehyde and primary amine hydrochlorides

Abstract A novel Mannich reaction between N- alkoxycarbonylpyrroles, formaldehyde and primary amine hydrochlorides is catalyzed by Y(OTf) 3 to afford a monoaminoalkylation product in good yield in aqueous media.

An Efficient One-Pot Synthesis of 2-Hydroxyalkyl Dithiocarbamates

Abstract In the presence of anhydrous potassium phosphate, epoxides reacted with carbon disulfide and primary or secondary amines in acetone to give the corresponding 2-hydroxyalkyl dithiocarbamates regioselectively in moderate to good yield.

Copper-mediated synthesis of N-fused heterocycles via Csp–S coupling reaction and 5-endo-dig cyclization sequence

A novel method was developed for the preparation of N-fused heterocycles via a Csp–S coupling reaction and a sequence of 5-endo-dig cyclization. This method involves the reaction of –NHC(S)NH-containing compounds and alkynes in the presence of CuCl and N,N′-dicyclohexylimidazolium chloride.

Unique spirocyclopiperazinium salt I: synthesis and structure–Activity relationship of spirocyclopiperazinium salts as analgesics

Based on the structure of compound 3, two series of spirocyclopiperazinium derivatives 7a-n and 10a-h were synthesized and evaluated for their in vivo analgesic and sedative activities. Compounds 7f and 10c were discovered to exhibit excellent analgesic activity. Structure-activity relationships revealed that anion of the quaternary salt affected the analgesic and sedative activity significantly; the allyl group is a most effective group among the compounds 7a-n; the electron-released substitute on the aromatic ring is favorable to increase the analgesic activity.

An efficient dipeptide-catalyzed direct asymmetric aldol reaction of equimolar reactants in solid media

The direct asymmetric aldol reactions of equivalent molar amounts of aldehydes and ketones were carried out at -20 degrees C over alkaline Al(2)O(3) with 20 mol % of Pro-Trp as catalyst and 20 mol % of N-methylmorpholine or 1,4-diazabicyclo[2.2.2]octane as additive. After simple and environmentally friendly work-up, moderate to high isolated yields (up to 95%), good diastereoselectivities (>99:1), and enantioselectivities (up to 98% ee) have been achieved for the reactions of different kinds of ketones with various aldehydes. The catalytic system could be reused without decrease of activity by addition of 10 mol % catalyst and base in the catalytic system.

Unique spirocyclopiperazinium salt. Part 2: synthesis and structure–activity relationship of dispirocyclopiperazinium salts as analgesics

Three series of spirocyclopiperazinium derivatives 5a-d, 6a-f and 17a-d were synthesized and evaluated for their in vivo analgesic activities. Compounds 5a, 17a and 17b exhibited excellent analgesic activity. Two important structure-activity relationships were observed from this study: (1) the quaternary ammonium functionality is a critical pharmacophore for analgesic activity; (2) it is important to adjust the lipophilic property of compounds to improve analgesic activity.

An Efficient Synthesis of Formylmethyl Piperidine-1-carbodithioate Diethyl Acetal and Analogs

Abstract The formylmethyl piperidine-1-carbodithioate diethyl acetal and its analogs were prepared from the reaction of different amines with carbon disulfide and bromoaldehyde acetal in the presence of anhydrous potassium phosphate under mild condition in excellent yield.

Novel Dithiocarbamic Acid Esters Derived from 6‐Aminomethyl‐4‐anilinoquinazolines and 6‐Aminomethyl‐4‐anilino‐3‐cyanoquinolines as Potent EGFR Inhibitors

Two series of dithiocarbamic acid esters, 4‐anilinoquinazoline‐6‐ylmethylcarbamodithioic acid esters and 3‐cyano‐4‐anilinoquinolin‐6‐ylmethylcarbamodithioic acid esters, were designed and synthesized. The effect of the synthesized compounds on cell proliferation was evaluated by MTT assay against three human cancer cell lines: MDA‐MB‐468, SK‐BR‐3 and HCT‐116. Most of the compounds are equally or more potent than the positive control lapatinib. Three compounds (14d, 14h and 14i) were identified as dual inhibitors of the EGFR and ErbB‐2 kinases and two compounds (14b and 14c) were identified as multi‐target kinase inhibitors, and they are very worthy of further study. Installation of the dithiocarbamic acid ester group at the 6‐position of 4‐anilinoquinazoline or 3‐cyano‐4‐anilinoquinoline could improve the inhibitory activity. Different dithiocarbamic acid ester groups significantly affect the activities.