Hequan Yao

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Name: 姚和权

Organization: China Pharmaceutical University , China

Department: State Key Laboratory of Natural Medicines

Title: NULL(PhD)

TOPICS

Physical Chemistry

Inorganic Chemistry

Chemicals
References

Accessing 1,3-Dienes via Palladium-Catalyzed Allylic Alkylation of Pronucleophiles with Skipped Enynes

Co-reporter:Shang Gao, Hao Liu, Chi Yang, Zhiyuan Fu, Hequan Yao, and Aijun Lin

Organic Letters September 15, 2017 Volume 19(Issue 18) pp:

Publication Date(Web):August 24, 2017

DOI:10.1021/acs.orglett.7b01960

An unprecedented palladium-catalyzed allylic alkylation of pronucleophiles with unactivated skipped enynes has been developed. This method provides a straightforward access to a wide array of 1,3-dienes without the need to preinstall leaving groups or employ extra oxidants. The reaction exhibited high atom economy, good functional group tolerance, excellent regioselectivities, and scalability. With D2O as cosolvent, deuterium could be incorporated in high efficiency.

Silver-Catalyzed Cascade 1,6-Addition/Cyclization of para-Quinone Methides with Propargyl Malonates: An Approach to Spiro[4.5]deca-6,9-dien-8-ones

Co-reporter:Zhenbo Yuan, Lina Liu, Rui Pan, Hequan Yao, and Aijun Lin

The Journal of Organic Chemistry August 18, 2017 Volume 82(Issue 16) pp:8743-8743

Publication Date(Web):July 18, 2017

DOI:10.1021/acs.joc.7b01400

An unprecedented silver-catalyzed cascade 1,6-addition/5-exo-dig cyclization reaction between para-quinone methides and propargyl malonates under mild reaction conditions has been described. This reaction provides an efficient method to construct versatile spiro[4.5]cyclohexadienones in moderate to excellent yields with high atom economy and scalability.

Antioxidant Properties of Novel Dimers Derived from Natural β-Elemene through Inhibiting H2O2-Induced Apoptosis

Co-reporter:Jichao Chen, Ruifan Wang, Tianyu Wang, Qilong Ding, Aliahmad Khalil, Shengtao Xu, Aijun Lin, Hequan Yao, Weijia Xie, Zheying Zhu, and Jinyi Xu

ACS Medicinal Chemistry Letters April 13, 2017 Volume 8(Issue 4) pp:443-443

Publication Date(Web):March 13, 2017

DOI:10.1021/acsmedchemlett.7b00035

A series of novel β-elemene dimer derivatives were synthesized and evaluated for their antioxidant activities. The results indicated that most of the target compounds showed more potent cytoprotective effects than positive control vitamin E. In particular, dimer D5 exhibited the strongest antioxidant activity, which was significantly superior to the active compound D1 obtained in our previous study. Besides, D5 did not produce obvious cytotoxicity in normal human umbilical vein endothelial cells (HUVECs) and increased the viability of HUVECs injured by H2O2 in a concentration-dependent manner. Further studies suggested that the cytoprotective action of D5 might be mediated, at least in part, by increasing the intracellular superoxide dismutase activity and nitric oxide secretion as well as decreasing the intracellular malonyldialdehyde content and lactate dehydrogenase release. Furthermore, D5 observably inhibited ROS generation and prevented H2O2-induced apoptosis in HUVECs possibly via inhibiting the activation of the MAPK signaling pathway.Keywords: antioxidant activity; apoptosis; dimer; MAPK pathway; β-Elemene;

Palladium-catalyzed Oxa-[4+2] Annulation of para-Quinone Methides

Co-reporter:Zhenbo Yuan;Rui Pan;He Zhang;Lina Liu;Aijun Lin

Advanced Synthesis & Catalysis 2017 Volume 359(Issue 23) pp:4244-4249

Publication Date(Web):2017/12/11

DOI:10.1002/adsc.201700978

AbstractA palladium-catalyzed oxa-[4+2] annulation of para-quinone methides with allyl carbonates bearing a nucleophilic alcohol side chain has been developed. This method provided an efficient strategy to the construction of 2-oxaspiro-cyclohexadienones via 1,6-conjugated addition-mediated allylation in moderate to good yields. Preliminary results on asymmetric derivatives promised potential in the synthesis of enantioenriched frameworks.

Tandem 1,6-addition/cyclization/vinylcyclopropane rearrangement at low temperature under metal-free conditions: an approach to spiro[4.5]cyclohexadienones

Co-reporter:Zhenbo Yuan;Kuo Gai;Youzhi Wu;Jie Wu;Aijun Lin

Chemical Communications 2017 vol. 53(Issue 24) pp:3485-3488

Publication Date(Web):2017/03/21

DOI:10.1039/C7CC00677B

A tandem 1,6-addition/cyclization/vinylcyclopropane rearrangement reaction (VCPR) of vinylogous para-quinone methides at low temperature under metal-free conditions has been disclosed for the first time. This method provides an efficient strategy for the construction of a range of spiro[4.5]cyclohexadienones in good yield, exhibiting good functional group tolerance as well as gram-scale capacity.

Palladium-catalyzed allylic alkylation with internal alkynes to construct C–C and C–N bonds in water

Co-reporter:Shang Gao;Hao Liu;Zijun Wu;Aijun Lin

Green Chemistry (1999-Present) 2017 vol. 19(Issue 8) pp:1861-1865

Publication Date(Web):2017/04/20

DOI:10.1039/C7GC00666G

A palladium-catalyzed system enabled efficient allylic alkylation with alkynes in water has been developed. This reaction presents an environmentally friendly strategy for constructing lots of allylic compounds with indolinones, ketones, amines as well as electron-rich aromatic compounds as nucleophiles. Moreover, the in situ formed arylallene intermediate adopting alkynes as starting materials omits the need for leaving groups and extra oxidants, showing high atom economy. The versatility of the developed reaction also lends itself to the incorporation of deuteriums by simply replacing H2O with D2O.

Pd(II)-Catalyzed oxidative dearomatization of indoles: substrate-controlled synthesis of indolines and indolones

Co-reporter:Xinxin Fang;Shang Gao;Zijun Wu;Aijun Lin

Organic Chemistry Frontiers 2017 vol. 4(Issue 2) pp:292-296

Publication Date(Web):2017/02/01

DOI:10.1039/C6QO00698A

A Pd(II)-catalyzed oxidative Wacker-type cyclization/dearomatization of 2,3-disubstituted indoles with molecular oxygen as the oxidant has been developed. This strategy provides straightforward access to diverse fused indolines bearing C2-oxygenated quaternary stereocenters with good functional group tolerance and high atom economy. Meanwhile, a Pd(II)-catalyzed oxidation/dearomatization of 2-substituted indoles is also presented, which enables the facile synthesis of indolones.

Design, synthesis and biological evaluation of novel nitric oxide-donating protoberberine derivatives as antitumor agents

Co-reporter:Jichao Chen, Tianyu Wang, Shengtao Xu, Aijun Lin, Hequan Yao, Weijia Xie, Zheying Zhu, Jinyi Xu

European Journal of Medicinal Chemistry 2017 Volume 132(Volume 132) pp:

Publication Date(Web):26 May 2017

DOI:10.1016/j.ejmech.2017.03.027

•Eighteen novel NO-donating protoberberine derivatives were synthesized.•Most compounds showed significantly enhanced in vitro anti-proliferative activity.•15a exhibited good selectivity between tumor cells and normal liver LO-2 cells.•The antitumor activity of 15a in HepG2 cells was diminished by an NO scavenger.•15a effectively inhibited liver tumor growth in an in vivo mouse model.A novel class of NO-donating protoberberine derivatives were synthesized and initially evaluated for their anti-hepatocellular carcinoma activities. Most of the compounds exhibited more potent activity against HepG2 cells than parent compounds berberine and palmatine. In particular, compound 15a exerted the strongest activity with an IC50 value of 1.36 μM. Moreover, most compounds released moderate levels of NO in vitro, and the antitumor activity of 15a in HepG2 cells was remarkably diminished by an NO scavenger. Interestingly, compound 15a displayed a broad-spectrum antitumor efficacy and possessed good selectivity between tumor cells (HepG2, SMMC-7721, HCT-116, HL-60) and normal liver LO-2 cells. The mechanism studies revealed that 15a blocked the G2 phase of the cell cycle and induced apoptosis of HepG2 cells by mitochondrial depolarization. Furthermore, 15a inhibited tumor growth in H22 liver cancer xenograft mouse model by 62.5% (w/w), which was significantly superior to parent compound palmatine (41.6%, w/w). Overall, the current study may provide a new approach for the discovery of novel antitumor agents.Download high-res image (207KB)Download full-size image

Novel hybrids of natural β-elemene bearing isopropanolamine moieties: Synthesis, enhanced anticancer profile, and improved aqueous solubility

Co-reporter:Jichao Chen, Tianyu Wang, Shengtao Xu, Aijun Lin, Hequan Yao, Weijia Xie, Zheying Zhu, Jinyi Xu

Fitoterapia 2017 Volume 120(Volume 120) pp:

Publication Date(Web):1 July 2017

DOI:10.1016/j.fitote.2017.05.002

A series of novel β-elemene isopropanolamine derivatives were synthesized and evaluated for their antitumor activity. The results indicated that all of the compounds showed stronger antiproliferative activities than β-elemene as well as improved aqueous solubility. In particular dimer 6q showed the strongest cytotoxicity against four tumor cell lines (SGC-7901, HeLa, U87 and A549) with IC50 values ranging from 4.37 to 10.20 μM. Moreover, combination of 6q with cisplatin exhibited a synergistic effect on these cell lines with IC50 values ranging from 1.21 to 2.94 μM, and reversed the resistance of A549/DPP cells with an IC50 value of 2.52 μM. The mechanism study revealed that 6q caused cell cycle arrest at the G2 phase and induced apoptosis of SGC-7901 cells through a mitochondrial-dependent apoptotic pathway. Further in vivo study in H22 liver cancer xenograft mouse model validated the antitumor activity of 6q with a tumor inhibitory ratio (TIR) of 60.3%, which was higher than that of β-elemene (TIR, 49.1%) at a dose of 60 mg/kg. Altogether, the potent antitumor activity of 6q in vitro and in vivo warranted further preclinical investigation for potential anticancer chemotherapy.Download high-res image (85KB)Download full-size image

Palladium-Catalyzed Dearomative Allylic Alkylation of Indoles with Alkynes To Synthesize Indolenines with C3-Quarternary Centers

Co-reporter:Shang Gao, Zijun Wu, Xinxin Fang, Aijun Lin, and Hequan Yao

Organic Letters 2016 Volume 18(Issue 15) pp:3906-3909

Publication Date(Web):July 21, 2016

DOI:10.1021/acs.orglett.6b01947

A palladium-catalyzed dearomative allylic alkylation of indoles with alkynes to construct indolenines with C3-quarternary centers was reported. The in situ formed arylallene intermediate omitted the need to install leaving groups on the allylic compounds and employ extra oxidants to oxidize the allylic C–H bonds. The reaction exhibited good functional group tolerance and high atom economy. Moreover, the reaction was further expanded to synthesize pyrroloindolines and furanoindolines.

Rh(III)-Catalyzed Cascade Annulation/C–H Activation of o-Ethynylanilines with Diazo Compounds: One-Pot Synthesis of Benzo[a]carbazoles via 1,4-Rhodium Migration

Co-reporter:Songjin Guo, Kai Yuan, Meng Gu, Aijun Lin, and Hequan Yao

Organic Letters 2016 Volume 18(Issue 20) pp:5236-5239

Publication Date(Web):October 5, 2016

DOI:10.1021/acs.orglett.6b02534

A Rh(III)-catalyzed cascade annulation/C–H activation of o-ethynylanilines with diazo compounds has been developed. This concise method allows for the rapid formation of a number of benzo[a]carbazoles in high yields, exhibiting good functional group tolerance and scalability. The key to the success of this approach involves one C–N bond and two C–C bond formation, and an aryl-to-aryl 1,4-rhodium migration.

[3 + 2] Cycloaddition Reaction of in Situ Formed Azaoxyallyl Cations with Aldehydes: An Approach to Oxazolidin-4-ones

Co-reporter:Kaifan Zhang, Chi Yang, Hequan Yao, and Aijun Lin

Organic Letters 2016 Volume 18(Issue 18) pp:4618-4621

Publication Date(Web):August 29, 2016

DOI:10.1021/acs.orglett.6b02254

A novel [3 + 2] cycloaddition reaction between in situ formed azaoxyallyl cations and aldehydes has been developed. This concise method allows the rapid formation of a number of oxazolidin-4-ones in high yields with good functional group tolerance at room temperature. Further transformation and late-stage modifications of drug molecules could also be achieved in good yields, highlighting the potential utility of the reaction.

Controllable Rh(III)-Catalyzed Annulation between Salicylaldehydes and Diazo Compounds: Divergent Synthesis of Chromones and Benzofurans

Co-reporter:Peng Sun, Shang Gao, Chi Yang, Songjin Guo, Aijun Lin, and Hequan Yao

Organic Letters 2016 Volume 18(Issue 24) pp:6464-6467

Publication Date(Web):December 1, 2016

DOI:10.1021/acs.orglett.6b03355

A Rh(III)-catalyzed annulation between salicylaldehydes and diazo compounds with controllable chemoselectivity is described. AgNTf2 favored benzofurans via a tandem C–H activation/decarbonylation/annulation process, while AcOH led to chromones through a C–H activation/annulation pathway. The reaction exhibited good functional group tolerance and scalability. Moreover, only a single regioisomer of benzofuran was obtained due to the in situ decarbonylation orientation effect.

Bifunctional Organo/Metal Cooperatively Catalyzed [3 + 2] Annulation of para-Quinone Methides with Vinylcyclopropanes: Approach to Spiro[4.5]deca-6,9-diene-8-ones

Co-reporter:Zhenbo Yuan, Weiwei Wei, Aijun Lin, and Hequan Yao

Organic Letters 2016 Volume 18(Issue 14) pp:3370-3373

Publication Date(Web):July 5, 2016

DOI:10.1021/acs.orglett.6b01512

A novel [3 + 2] annulation between para-quinone methides and vinylcyclopropanes for the synthesis of spiro[4.5]deca-6,9-diene-8-ones has been described. The palladium and phosphine–thiourea cooperative catalysis system played an important role in high yields and diastereoselectivities. The reaction exhibited good functional group tolerance and scalability.

Pd(II)-catalyzed intramolecular oxidative Heck dearomative reaction: approach to thiazole-fused pyrrolidinones with a C2-azaquarternary center

Co-reporter:Shang Gao, Chi Yang, Yue Huang, Lei Zhao, Xiaoming Wu, Hequan Yao and Aijun Lin

Organic & Biomolecular Chemistry 2016 vol. 14(Issue 3) pp:840-843

Publication Date(Web):23 Nov 2015

DOI:10.1039/C5OB01970B

A Pd(II)-catalyzed intramolecular oxidative Heck dearomative reaction for the construction of thiazole-fused pyrrolidinones with a C2-azaquarternary center and C3-exo-double bond has been achieved for the first time. The reaction exhibited good functional group tolerance and gram-scale capacity.

Rhodium-Catalyzed Hydroacylation of para-Quinone Methides with Salicylaldehydes: An Approach to α,α-Diaryl-2-Hydroxy Acetophenones

Co-reporter:Chi Yang, Shang Gao, Hequan Yao, and Aijun Lin

The Journal of Organic Chemistry 2016 Volume 81(Issue 23) pp:11956-11964

Publication Date(Web):October 28, 2016

DOI:10.1021/acs.joc.6b01859

A rhodium-catalyzed hydroacylation of para-quinone methides (p-QMs) with salicylaldehydes has been disclosed. This method allows for the construction of α,α-diaryl-2-hydroxy acetophenones through tandem C–H activation/C–C bond formation/aromatization process. Moreover, this unprecedented hydroacylation of trisubstituted alkenes exhibits good yields with broad functional group tolerance as well as gram-scale capacity.

Rh(III)-Catalyzed Redox-Neutral Annulation of Primary Benzamides with Diazo Compounds: Approach to Isoquinolinones

Co-reporter:Youzhi Wu, Peng Sun, Kaifan Zhang, Tie Yang, Hequan Yao, and Aijun Lin

The Journal of Organic Chemistry 2016 Volume 81(Issue 5) pp:2166-2173

Publication Date(Web):January 28, 2016

DOI:10.1021/acs.joc.5b02824

Reported herein is a Rh-catalyzed redox-neutral annulation of primary benzamides with diazo compounds, representing an efficient and economic protocol to isoquinolinones. The procedure exhibited good functional group tolerability, scalability, and regioselectivity, obviating the need for oxidants, and only environmentally benign N2 and H2O were released. Further utilization of the method provided an alternative route to functionalized isoquinolines.

Synthesis of spiro[2.5]octa-4,7-dien-6-one with consecutive quaternary centers via 1,6-conjugate addition induced dearomatization of para-quinone methides

Co-reporter:Kuo Gai, Xinxin Fang, Xuanyi Li, Jinyi Xu, Xiaoming Wu, Aijun Lin and Hequan Yao

Chemical Communications 2015 vol. 51(Issue 87) pp:15831-15834

Publication Date(Web):04 Sep 2015

DOI:10.1039/C5CC06287J

An efficient one-pot approach for the synthesis of spiro[2.5]octa-4,7-dien-6-ones by employing para-quinone methides has been developed. The reaction proceeded smoothly in high yields under mild conditions without the use of metals. Moreover, all products obtained herein contained two or three consecutive quaternary centers.

Palladium-catalyzed oxidative cross-coupling of azole-4-carboxylates with indoles: an approach to the synthesis of pimprinine

Co-reporter:Haipin Zhou, Kuo Gai, Aijun Lin, Jinyi Xu, Xiaoming Wu and Hequan Yao

Organic & Biomolecular Chemistry 2015 vol. 13(Issue 4) pp:1243-1248

Publication Date(Web):14 Nov 2014

DOI:10.1039/C4OB01844C

An efficient and straightforward method for the production of 5-(3-indolyl)azoles incorporating the privileged structures indoles and azoles via palladium-catalyzed double C–H bond cleavage under mild conditions was disclosed. As expected, this protocol provided an easy method for the synthesis of indole alkaloids pimprinine and WS-30581 A in moderate yields.

Design, synthesis and antitumor activity of triterpenoid pyrazine derivatives from 23-hydroxybetulinic acid

Co-reporter:Hengyuan Zhang, Yiwei Wang, Peiqing Zhu, Jie Liu, Shengtao Xu, Hequan Yao, Jieyun Jiang, Wencai Ye, Xiaoming Wu, Jinyi Xu

European Journal of Medicinal Chemistry 2015 Volume 97() pp:235-244

Publication Date(Web):5 June 2015

DOI:10.1016/j.ejmech.2015.04.057

•A series of pyrazine-fused 23-hydroxybetulinic acid derivatives was synthesized.•All of the synthesized compounds showed significant anti-proliferative activity.•Compound 12a caused G1 phase arrest and apoptosis on B16 cancer cells.•Compound 12a significantly inhibited the tumor growth in vivo.Pyrazine-fused 23-hydroxybetulinic acid was synthesized by introducing a pyrazine ring between C-2 and C-3 position and further modifications were carried out by substitution of C-28 carboxyl group by ester and amide linkage to enhance the antitumor activity. The biological screening results showed that all of the derivatives exhibited more significant antiproliferative activity than the parent compound. In particular compound 12a exhibited the most potent activity with IC50 values of 3.53 μM, 4.42 μM and 5.13 μM against cell lines SF-763, B16 and Hela, respectively. In the preliminary mechanism study, 12a caused cell arrest in G1 phase and significantly induced apoptosis of B16 cells in a dose-dependent manner. Furthermore, the in vivo antitumor activity of 12a was validated (tumor inhibitory ratio of 55.6% and 62.7%, respectively) in mice with H22 liver cancer and B16 melanoma.Compound 12a caused cell arrest in G1 phase and significantly induced apoptosis of B16 cells in a dose-dependent manner.

Synthesis and Biological Evaluation of Oxygen-containing Heterocyclic Ring-fused 23-Hydroxybetulinic Acid Derivatives as Antitumor Agents

Co-reporter:Hengyuan Zhang;Fangzheng Li;Peiqing Zhu;Jie Liu;Jieyun Jiang;Wencai Ye;Xiaoming Wu;Jinyi Xu

Chemical Biology & Drug Design 2015 Volume 86( Issue 4) pp:424-431

Publication Date(Web):

DOI:10.1111/cbdd.12543

A collection of isoxazole and oxadiazole substituted 23-hydroxybetulinic acid (HBA) derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited more potent antiproliferative activity than patent compound 23-hydroxybetulinic acid, especially 13e and 14a were about four- to sevenfold more potent against all tested cancer cell lines than 23-hydroxybetulinic acid. Furthermore, the in vivo antitumor activity of 13e and 14a was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure–activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.

1,6-Conjugated Addition-Mediated [2+1] Annulation: Approach to Spiro[2.5]octa-4,7-dien-6-one

Co-reporter:Zhenbo Yuan, Xinxin Fang, Xuanyi Li, Jie Wu, Hequan Yao, and Aijun Lin

The Journal of Organic Chemistry 2015 Volume 80(Issue 21) pp:11123-11130

Publication Date(Web):October 6, 2015

DOI:10.1021/acs.joc.5b01793

A formal 1,6-conjugated addition-mediated [2+1] annulation to synthesize spiro[2.5]octa-4,7-dien-6-one with p-quinone methides and sulfur ylides has been described. This domino-type process was highly diastereoselective and exhibited good functional group tolerance and scalability without the use of metals and bases.

Solvent-Controlled C2/C5-Regiodivergent Alkenylation of Pyrroles

Co-reporter:Youla Su;Shang Gao;Yue Huang;Dr. Aijun Lin;Dr. Hequan Yao

Chemistry - A European Journal 2015 Volume 21( Issue 44) pp:15820-15825

Publication Date(Web):

DOI:10.1002/chem.201502418

Abstract

A solvent-controlled C2/C5-selective alkenylation of 3,4-disubstituted pyrroles has been developed. The C3 substituent of pyrroles proved crucial to the regioselectivity. Substrates bearing directing groups at the C3 position exhibited excellent C2-selectivities in chelation-assisted CH activation in toluene or 1,4-dioxane. However, a DMSO/DMF solvent system could override the chelation effect of weak directing groups, such as carboxylate and carbonyl groups, favoring instead regioselectivity towards the more electron-rich C5 position. A series of 3-carboxylate and 3-carbonyl pyrroles were tested and showed moderate to good yields with good regioselectivities for both C2- and C5-alkenylation process.

Solvent-Controlled Switchable C–H Alkenylation of 4-Aryl-1H-pyrrole-3-carboxylates: Application to the Total Synthesis of (±)-Rhazinilam

Co-reporter:Youla Su, Haipin Zhou, Jiaxuan Chen, Jinyi Xu, Xiaoming Wu, Aijun Lin, and Hequan Yao

Organic Letters 2014 Volume 16(Issue 18) pp:4884-4887

Publication Date(Web):September 7, 2014

DOI:10.1021/ol5023933

A solvent-controlled switchable C–H alkenylation of 4-aryl-1H-pyrrole-3-carboxylates via a Pd(OAc)2 catalyzed oxidative Heck reaction was first realized. The corresponding C2 and C5 alkenylation products were obtained in good yields with high regioselectivities, respectively. The selective C5-alkenylation was successfully applied to the total synthesis of (±)-rhazinilam.

Synthesis and antitumor activity of novel 3-oxo-23-hydroxybetulinic acid derivatives

Co-reporter:Hengyuan Zhang, Peiqing Zhu, Jie Liu, Xue Yang, Shengtao Xu, Hequan Yao, Jieyun Jiang, Wencai Ye, Xiaoming Wu, Jinyi Xu

European Journal of Medicinal Chemistry 2014 Volume 87() pp:159-167

Publication Date(Web):24 November 2014

DOI:10.1016/j.ejmech.2014.09.058

•A series of 3-oxo-23-hydroxybetulinic acid derivatives was synthesized.•Most of the derivatives showed improved antitumor activity than parent compound.•Compound 10e displayed significant in vitro and in vivo antitumor activity.A series of novel derivatives of 3-oxo-23-hydroxybetulinic acid was designed, synthesized, and evaluated for their antiproliferative activity against a panel of cancer cell lines (HL-60, BEL-7402, SF-763, HeLa, B16 and A375). The results indicated that majority of the derivatives exhibited more significant antitumor activity than the parent compound. In particular compound 10e showed the most potent activity with IC50 values of 5.85, 6.23 and 7.22 μM against B16, SF-763 and BEL-7402 cells, respectively. Furthermore, 10e inhibited tumor growth by 51.8% and 62.7% (w/w) in H22 and B16 xenograft mouse models, comparable to cyclophosphamide and 5-fluorouracil, respectively.Compound 10e displayed significant antitumor activity against mice bearing H22 liver cancer and B16 melanoma.

Construction of indoloquinolinones via Pd(II)-catalyzed tandem CC/CN bond formation: application to the total synthesis of isocryptolepine

Co-reporter:Xuebing Chen, Peng Sun, Jinyi Xu, Xiaoming Wu, Lingyi Kong, Hequan Yao, Aijun Lin

Tetrahedron Letters 2014 Volume 55(Issue 51) pp:7114-7117

Publication Date(Web):17 December 2014

DOI:10.1016/j.tetlet.2014.11.008

Construction of indoloquinolinone skeleton via Pd-catalyzed tandem CC/CN bond formation has been achieved in moderate to good yields. The method was applied toward the total synthesis of the bioactive natural product isocryptolepine in good overall yields.

Facile construction of pyrrolophenanthridone skeleton via a one-pot intramolecular Heck reaction and oxidation

Co-reporter:Wei Cong, Lei Zhao, Xiaoming Wu, Jinyi Xu, Hequan Yao

Tetrahedron 2014 70(2) pp: 312-317

Publication Date(Web):

DOI:10.1016/j.tet.2013.11.053

Design, synthesis, and biological evaluation of 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives as potential antihypertensive candidates

Co-reporter:Jie Liu, Qin Liu, Xue Yang, Shengtao Xu, Hengyuan Zhang, Renren Bai, Hequan Yao, Jieyun Jiang, Mingqin Shen, Xiaoming Wu, Jinyi Xu

Bioorganic & Medicinal Chemistry 2013 Volume 21(Issue 24) pp:7742-7751

Publication Date(Web):15 December 2013

DOI:10.1016/j.bmc.2013.10.017

A series of novel 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives were designed and synthesized to develop new angiotensin II subtype 2 (AT2) receptor agonists as novel antihypertensive candidates. It was found that 14f (IC50 = 0.4 nM) and 15e (IC50 = 5.0 nM) displayed potent AT2 receptor affinity and selectivity in binding assays. Biological evaluation in vivo suggested that 14f is obviously superior to that of reference drug losartan in RHRs, and meanwhile, 14f has no significant impact on heart rate. The interesting activities of these compounds may make them promising candidates as antihypertensive agents.A series of novel 1,2,4-triazole bearing 5-substituted biphenyl-2-sulfonamide derivatives were designed and synthesized to develop new angiotensin II subtype 2 (AT2) receptor agonists as novel antihypertensive candidates. It was found that 14f (IC50 = 0.4 nM) and 15e (IC50 = 5.0 nM) displayed potent AT2 receptor affinity and selectivity in binding assays. Biological evaluation in vivo suggested that 14f is obviously superior to that of reference drug losartan in RHRs, and meanwhile, 14f has no significant impact on heart rate. The interesting activities of these compounds may make them promising candidates as antihypertensive agents.

Aryl–aryl coupling via palladium-catalyzed C–P/C–H bond cleavage

Co-reporter:Ziyuan Li, Haipin Zhou, Jinyi Xu, Xiaoming Wu, Hequan Yao

Tetrahedron 2013 69(15) pp: 3281-3286

Publication Date(Web):

DOI:10.1016/j.tet.2013.02.001

Direct C3-alkenylation of pyridin-4(1H)-one via oxidative Heck coupling

Co-reporter:Guangling Zhang, Ziyuan Li, Yue Huang, Jinyi Xu, Xiaoming Wu, Hequan Yao

Tetrahedron 2013 69(3) pp: 1115-1119

Publication Date(Web):

DOI:10.1016/j.tet.2012.11.061

Efficient Construction of Fused Indolines with a 2-Quaternary Center via an Intramolecular Heck Reaction with a Low Catalyst Loading

Co-reporter:Lei Zhao, Ziyuan Li, Lin Chang, Jinyi Xu, Hequan Yao, and Xiaoming Wu

Organic Letters 2012 Volume 14(Issue 8) pp:2066-2069

Publication Date(Web):March 30, 2012

DOI:10.1021/ol300584m

An efficient construction of fused indolines with a 2-quaternary center through a palladium-catalyzed intramolecular Heck reaction of N-(2(2-halobenzoxyl)-2,3-disubstituted indoles is disclosed. This protocol provided a straightforward access to diverse fused indolines with good functional group tolerance.

Pd(II)-catalyzed direct C5-arylation of azole-4-carboxylates through double C–H bond cleavage

Co-reporter:Ziyuan Li, Ling Ma, Jinyi Xu, Lingyi Kong, Xiaoming Wu and Hequan Yao

Chemical Communications 2012 vol. 48(Issue 31) pp:3763-3765

Publication Date(Web):21 Feb 2012

DOI:10.1039/C2CC00081D

The first palladium-catalyzed direct C5-arylation of azole-4-carboxylates with simple unactivated arenes through double C–H bond cleavage is realized. This protocol provided a straightforward access to diverse 5-arylsubstituted azole-4-carboxylic derivatives with good functional group tolerance.

Concise total syntheses of Marinoquinolines A–C

Co-reporter:Lijun Ni, Ziyuan Li, Fan Wu, Jinyi Xu, Xiaoming Wu, Lingyi Kong, Hequan Yao

Tetrahedron Letters 2012 Volume 53(Issue 10) pp:1271-1274

Publication Date(Web):7 March 2012

DOI:10.1016/j.tetlet.2011.12.124

The first concise total syntheses of pyrroloquinoline natural products, Marinoquinolines A–C, have been achieved in six linear steps from commercially available starting materials. The key steps were a reaction between (p-tolylsulfonyl)methylisocyanide (TosMIC) and α, β-unsaturated ester under basic condition to prepare the pyrrole moiety and Morgen-Walls reaction to construct quinoline ring.

Highly efficient oxidation of 2-imidazoline-5-carboxylic derivatives to imidazole-5-carboxylic derivatives by dioxygen

Co-reporter:Yue Huang, Xiaodong Zu, Fan Wu, Jinyi Xu, Xiaoming Wu, Hequan Yao

Tetrahedron 2012 68(14) pp: 3123-3128

Publication Date(Web):

DOI:10.1016/j.tet.2012.01.025

Oxidation of 1-benzyldihydroisoquinolines or 1-benzyltetrahydroisoquinolines with dioxygen to 1-benzoylisoquinolines

Co-reporter:Haifeng Gan, Yunyu Lu, Yue Huang, Lijun Ni, Jinyi Xu, Hequan Yao, Xiaoming Wu

Tetrahedron Letters 2011 Volume 52(Issue 12) pp:1320-1324

Publication Date(Web):23 March 2011

DOI:10.1016/j.tetlet.2011.01.058

An environmental-benign methodology to synthesize 1-benzoylisoquinolines from 1-benzyl-3, 4-dihydroisoquinolines or 1-benzyl-1,2,3,4-tetrahydroisoquinolines using dioxygen as an oxidant was developed. This methodology in combination with Bischler-Napieralski reaction leads to a facile synthesis of 1-benzoylisoquinolines from phenylacetic acids and phenylethanamines.

First total synthesis of tenuifolin via PIFA mediated oxidative biaryl coupling

Co-reporter:Changhua Tang, Ziyuan Li, Yiyun Wang, Jinyi Xu, Lingyi Kong, Hequan Yao, Xiaoming Wu

Tetrahedron Letters 2011 Volume 52(Issue 26) pp:3275-3278

Publication Date(Web):29 June 2011

DOI:10.1016/j.tetlet.2011.04.069

The first total synthesis of a sesquiterpenoid, tenuifolin, was achieved in seven linear steps. Phenyliodine(III) bis(trifluoacetate) (PIFA) mediated oxidative biaryl coupling was employed as a key step to construct the central seven-membered ring with a double bond. The double bond formation was also exploited.

Palladium(II)-catalyzed oxidative Heck coupling of thiazole-4-carboxylates

Co-reporter:Ziyuan Li, Ling Ma, Changhua Tang, Jinyi Xu, Xiaoming Wu, Hequan Yao

Tetrahedron Letters 2011 Volume 52(Issue 43) pp:5643-5647

Publication Date(Web):26 October 2011

DOI:10.1016/j.tetlet.2011.08.088

Oxidative Heck coupling of thiazole-4-carboxylates via palladium(II)-catalyzed C–H bond activation has been achieved in moderate to good yields. No ligand, and no acidic additive were used in the reaction. The results showed that this protocol tolerated a series of substitutions on the thiazole ring. A preliminary attempt of direct arylation with p-xylene via Pd(II)-catalyzed C–H bond activation has also been done.

Copper(II)-catalyzed oxidation of 4-carboxythiazolines and 4-carboxyoxazolines to 4-carboxythiazoles and 4-carboxyoxazoles

Co-reporter:Yiyun Wang, Ziyuan Li, Yue Huang, Changhua Tang, Xiaoming Wu, Jinyi Xu, Hequan Yao

Tetrahedron 2011 67(38) pp: 7406-7411

Publication Date(Web):

DOI:10.1016/j.tet.2011.07.016

Efficient palladium(II)-catalyzed homocoupling of thiazole-4-carboxylic or oxazole-4-carboxylic derivatives

Co-reporter:Ziyuan Li, Yiyun Wang, Yue Huang, Changhua Tang, Jinyi Xu, Xiaoming Wu, Hequan Yao

Tetrahedron 2011 67(31) pp: 5550-5555

Publication Date(Web):

DOI:10.1016/j.tet.2011.05.123

Environmental-benign oxidation of 2-oxazolines to oxazoles by dioxygen as the sole oxidant

Co-reporter:Yue Huang, Lijun Ni, Haifeng Gan, Yu He, Jinyi Xu, Xiaoming Wu, Hequan Yao

Tetrahedron 2011 67(11) pp: 2066-2071

Publication Date(Web):

DOI:10.1016/j.tet.2011.01.050

Synthesis of 3-Benzoyl Acrylates/Acrylamides via Dehydrogenation of 3-Benzoyl Propionates/Propionamides Using IBX/p-TsOH

Co-reporter:Ziyuan Li;Yiyun Wang;Changhua Tang;Jinyi Xu;Xiaoming Wu

Chinese Journal of Chemistry 2010 Volume 28( Issue 7) pp:1301-1305

Publication Date(Web):

DOI:10.1002/cjoc.201090225

Abstract

Dehydrogenation by IBX/p-TsOH is applied to the conversion of 3-benzoyl propionates/propionamides to 3-benzoyl acrylates/acrylamides in moderate to excellent yields. The reaction time for the dehydrogenation of 3-benzoyl propionamides was remarkably shorter than that for the dehydrogenation of esters.

Oxidation of 4-carboxylate thiazolines to 4-carboxylate thiazoles by molecular oxygen

Co-reporter:Yue Huang, Haifeng Gan, Shang Li, Jinyi Xu, Xiaoming Wu, Hequan Yao

Tetrahedron Letters 2010 Volume 51(Issue 13) pp:1751-1753

Publication Date(Web):31 March 2010

DOI:10.1016/j.tetlet.2010.01.091

A facile and environment-benign oxidation by molecular oxygen was applied for the conversion of 4-carboxylate thiazolines to 4-carboxylate thiazoles. The substituent effect on thiazoline ring was investigated. It was found that electron-poor group on the thiazoline ring could facilitate the oxidation.

Stereoselective Synthesis of Tetrahydropyran D-Ring of Methyl Sartortuoate

Co-reporter:Hequan Yao;Yuan Gao;Peng Liu;Xingxiang Xu

Chinese Journal of Chemistry 2009 Volume 27( Issue 10) pp:2025-2030

Publication Date(Web):

DOI:10.1002/cjoc.200990340

Abstract

A stereoselective synthesis of functionalized tetrahydropyran D-ring of methyl sartortuoate (1) was achieved starting from geraniol in a high yield. Sharpless asymmetric kinetic resolution, asymmetric dihydroxylation as well as asymmetric epoxidation were applied as key steps to establish all the four stereocenters of the D-ring.

Organocatalyzed Asymmetric 1,6-Conjugate Addition of para-Quinone Methides with Dicyanoolefins

Co-reporter:Xuanyi Li; Xiuyan Xu; Weiwei Wei; Aijun Lin

Organic Letters () pp:

Publication Date(Web):January 13, 2016

DOI:10.1021/acs.orglett.5b03471

A chiral thiourea catalyzed asymmetric 1,6-conjugate addition of para-quinone methides with dicyanoolefins has been developed. The reaction provided an efficient approach to the synthesis of chiral diarylmethine skeletons in good yields (up to 99% yield) with high diastereo- and enantioselectivity (>20:1 dr and up to 99.5:0.5 er), also on a gram scale. The preliminary mechanistic study showed that the remote stereocontrol was achieved through intermolecular hydrogen-bond interaction between the chiral thiourea catalyst and the para-quinone methides directly for the first time.

Cu(I)-Catalyzed oxidative homo-coupling of thiazoline-4-carboxylates: synthesis of 4,4′-bithiazoline derivatives

Co-reporter:Xinxin Fang, Kaifan Zhang, Hequan Yao and Yue Huang

Organic & Biomolecular Chemistry 2016 - vol. 14(Issue 34) pp:NaN8034-8034

Publication Date(Web):2016/08/01

DOI:10.1039/C6OB01471B

Cu(I)-Catalyzed oxidative homo-coupling of thiazoline-4-carboxylates with good functional group tolerance has been developed. The methodology presented an efficient method to directly construct vicinal carbon-hetero quaternary centers existing in numerous functional molecules and could be applied to the synthesis of 4,4′-bithiazoles which are difficult to prepare by direct C–H activation.

Tandem 1,6-addition/cyclization/vinylcyclopropane rearrangement at low temperature under metal-free conditions: an approach to spiro[4.5]cyclohexadienones

Co-reporter:Zhenbo Yuan, Kuo Gai, Youzhi Wu, Jie Wu, Aijun Lin and Hequan Yao

Chemical Communications 2017 - vol. 53(Issue 24) pp:NaN3488-3488

Publication Date(Web):2017/02/21

DOI:10.1039/C7CC00677B

Pd(II)-Catalyzed oxidative dearomatization of indoles: substrate-controlled synthesis of indolines and indolones

Co-reporter:Xinxin Fang, Shang Gao, Zijun Wu, Hequan Yao and Aijun Lin

Inorganic Chemistry Frontiers 2017 - vol. 4(Issue 2) pp:NaN296-296

Publication Date(Web):2016/12/01

DOI:10.1039/C6QO00698A

Synthesis of spiro[2.5]octa-4,7-dien-6-one with consecutive quaternary centers via 1,6-conjugate addition induced dearomatization of para-quinone methides

Co-reporter:Kuo Gai, Xinxin Fang, Xuanyi Li, Jinyi Xu, Xiaoming Wu, Aijun Lin and Hequan Yao