Wenjun Wu

Name:

Organization: Northwest Agriculture & Forestry University

Department: College of Science

Title:

Chemicals
References

Discovery of potent and selective GIRK1/2 modulators via ‘molecular switches’ within a series of 1-(3-cyclopropyl-1-phenyl-1H-pyrazol-5-yl)ureas

Co-reporter:Wandong Wen, Wenjun Wu, C. David Weaver, Craig W. Lindsley

Bioorganic & Medicinal Chemistry Letters 2014 Volume 24(Issue 21) pp:5102-5106

Publication Date(Web):1 November 2014

DOI:10.1016/j.bmcl.2014.08.061

This Letter describes the on-going SAR efforts based on ML297, a potent, efficacious and selective GIRK1/2 activator (∼10-fold vs GIRK1/4 and inactive on GIRK2/3) via an iterative parallel synthesis approach. The chemical optimization at the 3-position of pyrazole within ML297 indicated that various functionalized 3-cyclopropyl moieties modulated GIRK pharmacology between inhibitor/activator within a series of 1-(3-cyclopropyl-1-phenyl-1H-pyrazol-5-yl)ureas. Importantly, novel ‘molecular switches’ that modulated the mode of pharmacology from inhibitor to activator was discovered on both the 3-cyclopropyl and N-phenyl moiety of the pyrazole core, providing the first highly selective GIRK1/2 activator.

Substituted indoles as selective protease activated receptor 4 (PAR-4) antagonists: Discovery and SAR of ML354

Co-reporter:Wandong Wen, Summer E. Young, Matthew T. Duvernay, Michael L. Schulte, Kellie D. Nance, Bruce J. Melancon, Julie Engers, Charles W. Locuson II, Michael R. Wood, J. Scott Daniels, Wenjun Wu, Craig W. Lindsley, Heidi E. Hamm, Shaun R. Stauffer

Bioorganic & Medicinal Chemistry Letters 2014 24(19) pp: 4708-4713

Publication Date(Web):

DOI:10.1016/j.bmcl.2014.08.021

Rhodium-Catalyzed Highly Regioselective Hydroaminomethylation of Styrenes with Tetraphosphorus Ligands

Co-reporter:Shengkun Li, Kexuan Huang, Jiwen Zhang, Wenjun Wu, and Xumu Zhang

Organic Letters 2013 Volume 15(Issue 12) pp:3078-3081

Publication Date(Web):June 3, 2013

DOI:10.1021/ol4012635

The highly linear-selective hydroaminomethylation of styrenes is very challenging. Herein, an efficient, highly chemoselective, and linear-selective hydroaminomethylation (l/b up to >99:1) of styrenes using Rh(nbd)2SbF6 with a pyrrole-based 3,3′,5,5′-substituted tetraphosphorus ligand is documented. This is in sharp contrast to other available processes leading to branched amines and provides a novel atom economic approach to 3-arylpropylamines.

Cascade Synthesis of Fenpiprane and Related Pharmaceuticals via Rhodium-Catalyzed Hydroaminomethylation

Co-reporter:Shengkun Li, Kexuan Huang, Jiwen Zhang, Wenjun Wu, and Xumu Zhang

Organic Letters 2013 Volume 15(Issue 5) pp:1036-1039

Publication Date(Web):February 14, 2013

DOI:10.1021/ol303483t

A novel rhodium catalytic system with Naphos as ligand was developed for an efficient hydroaminomethylation of 1,1-diphenylethene under relatively mild conditions. This will allow for an atom-economic and environmentally benign synthesis of fenpiprane and related pharmaceuticals.

Discovery of ‘molecular switches’ within a GIRK activator scaffold that afford selective GIRK inhibitors

Co-reporter:Wandong Wen, Wenjun Wu, Ian M. Romaine, Kristian Kaufmann, Yu Du, Gary A. Sulikowski, C. David Weaver, Craig W. Lindsley

Bioorganic & Medicinal Chemistry Letters 2013 Volume 23(Issue 16) pp:4562-4566

Publication Date(Web):15 August 2013

DOI:10.1016/j.bmcl.2013.06.023

This letter describes a multi-dimensional SAR campaign based on a potent, efficacious and selective GIRK1/2 activator (∼10-fold versus GIRK1/4 and inactive on nonGIRK 1-containing GIRKs, GIRK 2 or GIRK2/3). Further chemical optimization through an iterative parallel synthesis effort identified multiple ‘molecular switches’ that modulated the mode of pharmacology from activator to inhibitor, as well as engendering varying selectivity profiles for GIRK1/2 and GIRK1/4. Importantly, these compounds were all inactive on nonGIRK1 containing GIRK channels. However, SAR was challenging as subtle structural modifications had large effects on both mode of pharmacology and GIRK1/2 and GIRK1/4 channel selectivity.

Rh-Catalyzed Highly Enantioselective Hydrogenation of Nitroalkenes under Basic Conditions

Co-reporter:Shengkun Li;Kexuan Huang;Jiwen Zhang;Dr. Wenjun Wu;Dr. Xumu Zhang

Chemistry - A European Journal 2013 Volume 19( Issue 33) pp:10840-10844

Publication Date(Web):

DOI:10.1002/chem.201301049

Simultaneous Identification of Multiple Celangulins from the Root Bark of Celastrus angulatus Using High-performance Liquid ChromatographyDiode Array DetectorElectrospray IonisationTandem Mass Spectrometry

Co-reporter:Shaopeng Wei;Jinming Gao;Zhiqin Ji;Jiwen Zhang

Phytochemical Analysis 2012 Volume 23( Issue 1) pp:23-33

Publication Date(Web):

DOI:10.1002/pca.1321

ABSTRACT

Introduction

Celangulins are a small family of β-dihydroagarofuran sesquiterpenoids endowed with diverse polyoxygenated polyol esters and various biological properties. Since our research focuses on celangulins, the development of rapid and sensitive online analytical methods to analyse and characterise them is of great significance.

Objective

To develop an HPLC-DAD-ESI-MS/MS method capable of simple and rapid analysis of celangulins in crude extract of root bark of C. angulatus extracts.

Methodology

High-performance liquid chromatography coupled with a diode array detector and electrospray ionisation tandem mass spectrometry was established for the efficient and rapid identification of the celangulins. Chromatographic separations of celangulins were performed on a Hypersil Gold C₁₈ reverse-phase column by gradient elution with acetonitrile–water as mobile phase at a flow-rate 0.2 mL/min.

Results

ESI/MS/MS analysis of sodium adduct ion ([M + Na]⁺) of each celangulin shows that all the celangulins produced very similar fragmentation profiles, and that the characteristic fragments at m/z 245, m/z 229 and m/z 231 were defined as the diagnostic ions for celangulins. Simultaneously, 46 components in the extracts of this plant were separated, and 36 of them were characterised as celangulins by online ESI/MS/MS and by comparing their retention times, UV and MS spectra with those of authentic compounds.

Conclusion

Highly Enantioselective Hydrogenation of ,-Disubstituted Nitroalkenes

Co-reporter:Shengkun Li;Kexuan Huang;Bonan Cao;Jiwen Zhang; Wenjun Wu; Xumu Zhang

Angewandte Chemie International Edition 2012 Volume 51( Issue 34) pp:8573-8576

Publication Date(Web):

DOI:10.1002/anie.201202715

Larvicidal activity of lignans from Phryma leptostachya L. against Culex pipiens pallens

Co-reporter:Xin-min Xiao;Zhao-nong Hu;Bao-jun Shi;Shao-peng Wei;Wen-jun Wu

Parasitology Research 2012 Volume 110( Issue 3) pp:1079-1084

Publication Date(Web):2012 March

DOI:10.1007/s00436-011-2591-1

The larvicidal activity of crude petroleum ether, ethyl acetate, and methanol extracts of the whole plants of Phryma leptostachya L. was assayed for its toxicity against the early fourth instar larvae of Culex pipiens pallens. The larval mortality was observed after 24 h of exposure. Among three solvent extracts from Phyrma leptostachya L., the petroleum ether extract exhibited the best larvicidal activity. The corresponding LC50 values of petroleum ether, ethyl acetate, and methanol extracts were 3.23, 5.23, and 61.86 ppm against the early fourth instar larvae of Culex pipiens pallens. The petroleum ether extract was successively subjected to column chromatography and preparative high performance liquid chromatography, and yielded the three lignans, phrymarolin-I, haedoxane A, and haedoxane E, which were isolated and identified as new mosquito larvicidal compounds. Phrymarolin-I, haedoxane A, and haedoxane E showed high larvicidal activity, for which the lethal doses LC50 were estimated at 1.21, 0.025, and 0.15 ppm against the early fourth instar larvae of Culex pipiens pallens, respectively. The structures were elucidated by analyses of IR, UV, MS, and NMR spectral data. This is the first report on the mosquito larvicidal activity of the three compounds, phrymarolin-I, haedoxane A, and haedoxane E from Phyrma leptostachya L.

Highly Enantioselective Hydrogenation of ,-Disubstituted Nitroalkenes

Co-reporter:Shengkun Li;Kexuan Huang;Bonan Cao;Jiwen Zhang; Wenjun Wu; Xumu Zhang

Angewandte Chemie 2012 Volume 124( Issue 34) pp:8701-8704

Publication Date(Web):

DOI:10.1002/ange.201202715

Isolation, biological evaluation and 3D-QSAR studies of insecticidal/narcotic sesquiterpene polyol esters

Co-reporter:Shao-peng Wei;Zhi-qin Ji;Hui-xiao Zhang;Ji-wen Zhang

Journal of Molecular Modeling 2011 Volume 17( Issue 4) pp:681-693

Publication Date(Web):2011 April

DOI:10.1007/s00894-010-0765-x

For the first time, a set of (43) natural sesquiterpene polyol esters isolated from the root bark of Celastrus angulatus Maxim and Euonymus japonicus Thunb were subjected to 3D-QSAR comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies, with the aim of proposing novel sesquiterpene-based compounds with optimal narcotic or insecticidal activities. The established 3D-QSAR models exhibit reasonable statistical quality and prediction capabilities, with internal cross-validated Q2 values of ∼0.5 and external predicted R2 values of >0.9, respectively. The relative contributions of the steric/electrostatic fields of the 3D-QSAR models show that the electronic effect governs the narcotic activities of the molecules, but the hybrid effect of the electrostatic and hydrophobic interactions is more influential in the insecticidal activities of the compounds. These findings may have valuable implications for the development of novel natural insecticides.

Two New Sesquiterpene Polyol Esters from Celastrus angulatus

Co-reporter:Shao-Peng Wei;Wen-Jun Wu;Zhi-Qin Ji;Ji-Wen Zhang;Yong-Ze Guo;Jian Xue

Helvetica Chimica Acta 2010 Volume 93( Issue 9) pp:1844-1850

Publication Date(Web):

DOI:10.1002/hlca.200900473

Abstract

Two novel sesquiterpene polyol esters with a dihydro-β-agarofuran (=(3R,5aS,9R,9aS)-octahydro-2,2,5a,9-tetramethyl-2H-3,9a-methano-1-benzoxepin) skeleton, (1α,2α,4β,8α,9α)-1,2,8,12-tetrakis(acetyloxy)-9-(furoyloxy)-4-hydroxydihydro-β-agarofuran (1) and (1α,2α,6β,8α,9α)-1,2,6,8,12-pentakis(acetyloxy)-9-(benzoyloxy)dihydro-β-agarofuran (2), and the three known compounds (1α,2α,4β,6β,8α,9β)-1,2,6-tris(acetyloxy)-9-(benzoyloxy)-4-hydroxy-8,12-bis(isobutyryloxy)dihydro-β-agarofuran (3), (1α, 2α,4β,6β,8α,9β)-1,2,6,8-tetrakis(acetyloxy)-9-(furoyloxy)-4-hydroxy-12-isobutyryloxy)dihydro-β-agarofuran (4), and (1α,2α,4β,6β,8α,9β)-1,2,6-tris(acetyloxy)-9-(benzoyloxy)-4-hydroxy-8-(isobutyryloxy)-12-[(2-methylbutanoyl)oxy]dihydro-β-agarofuran (5) were isolated from the root bark of Celastrus angulatus. Their chemical structures were elucidated by analyses of their MS and NMR data.

NW-G01, a novel cyclic hexapeptide antibiotic, produced by Streptomyces alboflavus 313: II. Structural elucidation

Co-reporter:Zhengyan Guo, Zhiqin Ji, Jiwen Zhang, Jing Deng, Ling Shen, Wei Liu and Wenjun Wu

The Journal of Antibiotics 2010 63(5) pp:231-235

Publication Date(Web):April 9, 2010

DOI:10.1038/ja.2010.24

NW-G01 is a novel cyclic hexapeptide antibiotic produced by Streptomyces alboflavus 313. Its relative structure was established by HR-ESI-MS, IR, 1D and 2D NMR techniques, the absolute structure was determined using a combination of single-crystal X-ray diffraction and Marfey’s method finally. The antibiotic consists of L-valine, (3S)- and (3R)-piperazic acids, N-methyl-D-alanine and (2S,3aR,8aS)-6-chloro-3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid.

NW-G01, a novel cyclic hexadepsipeptide antibiotic, produced by Streptomyces alboflavus 313: I. Taxonomy, fermentation, isolation, physicochemical properties and antibacterial activities

Co-reporter:Zhengyan Guo, Ling Shen, Zhiqin Ji, Jiwen Zhang, Luzhi Huang and Wenjun Wu

The Journal of Antibiotics 2009 62(4) pp:201-205

Publication Date(Web):March 6, 2009

DOI:10.1038/ja.2009.15

NW-G01, a novel cyclic hexadepsipeptide antibiotic, was isolated by macroporous resin and silica gel column chromatography and HPLC from the fermentation broth of strain no. 313. The producing strain was identified as Streptomyces alboflavus on the basis of the morphological characteristics, physiological property and 16S rDNA gene sequence analysis. NW-G01 exhibited strong antibacterial activity against Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, methicillin-resistant S. aureus, and their MIC values were 3.90, 3.90, 7.81 and 7.81 μg ml−1, respectively.