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Wang, Qiu

Overview:

Research in the Wang group aims to answer fundamental questions that lie at the interface of chemistry and biology. In particular, we are interested in developing small-molecule based probes and methods to understand the cause of disease with an emphasis on identifying potential therapeutic agents towards cancer and neurodegenerative disorders.



Bioactive molecules as probes in human biology and disease. Starting from naturally occurring molecules that possess unique anti-cancer activity or neuroprotective/neurotrophic activities, our research incorporates synthetic chemistry and biological efforts to expedite discovery of novel bioactive molecules and to facilitate the study of their biological properties. Chemistry efforts will emphasize the development of modular approaches to target molecules and new methodologies to maximize synthetic efficiency. Biological studies will focus on profiling the activities of selected compounds and identifying their mode of action.
Epigenetic modifying enzymes as novel therapeutic targets. We are interested in developing small-molecule regulators of epigenetics modifications, the new frontier in understanding and treatment of disease. For example, research will be directed towards identifying small-molecule modulators of arginine methylation and uncovering their regulatory pathways. Discovery of such molecules will provide powerful tools to interrogate the physiological roles of arginine methylation and offer potential lead molecules for novel therapies to contribute to a new era of epigenetic-based drugs.
New chemical tools for biomolecule labeling and target identification. Our research also involves the development of new chemical tools to enable selective detection of the temporal and spatial small-molecule ligand-biomolecule interactions in vitro and in vivo. Towards this end, we will design and synthesize photoaffinity cross-linking tools to label methyltransferases, their substrates, and their binding partners.

Overall, the research in the Wang group involves the interplay of these three complementary areas and integrates the principles of synthetic chemistry, assay development, molecular and cell biology, genetics, and proteomics. Through this interdisciplinary approach, we will create a small-molecule toolbox for studying genes and pathways of importance to cancer and neurodegenerative disorders.

Positions:

Assistant Professor of Chemistry

Chemistry
Trinity College of Arts & Sciences

Faculty Network Member of the Duke Institute for Brain Sciences

Duke Institute for Brain Sciences
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1999

B.S. — Wuhan University (China)

Ph.D. 2005

Ph.D. — Emory University

News:

Grants:

Developing New Strategies and Chemical Probes for Molecular Imaging

Administered By
Chemistry
AwardedBy
Camille & Henry Dreyfus Foundation, Inc.
Role
Principal Investigator
Start Date
June 01, 2016
End Date
May 31, 2021

New Methods for the Synthesis and Study of Bioactive Nitrogen-Containing Molecules

Administered By
Chemistry
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
January 05, 2017
End Date
December 31, 2020

Pharmacological Sciences Training Program

Administered By
Pharmacology & Cancer Biology
AwardedBy
National Institutes of Health
Role
Participating Faculty Member
Start Date
July 01, 1975
End Date
June 30, 2020

CAREER: Harnessing nitrogen-heteroatom bonds for unsaturated carbon-carbon bond difunctionalization

Administered By
Chemistry
AwardedBy
National Science Foundation
Role
Principal Investigator
Start Date
June 01, 2015
End Date
May 31, 2020

2016 Sloan Research Fellowship

Administered By
Chemistry
AwardedBy
Alfred P. Sloan Foundation
Role
Principal Investigator
Start Date
September 15, 2016
End Date
September 14, 2018

GAANN - Department of Chemistry

Administered By
Chemistry
AwardedBy
Department of Education
Role
Mentor
Start Date
September 01, 2015
End Date
August 31, 2018

MRI: Acquisition of a Triple Quadrupole LC/MS System

Administered By
Chemistry
AwardedBy
National Science Foundation
Role
Major User
Start Date
August 01, 2015
End Date
July 31, 2018

Developing small-molecule probes for protein arginine methyltransferases

Administered By
Chemistry
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
July 01, 2015
End Date
June 30, 2018

Screening and identification of beta-arrestin biased dopamine receptor ligands for PD symptom therapy.

Administered By
Cell Biology
AwardedBy
Michael J. Fox Foundation for Parkinson's Research
Role
Co Investigator
Start Date
March 01, 2016
End Date
October 31, 2016

Facile Access to Vicinal Amino-Heteroatom Functionalities From N-X Bonds

Administered By
Chemistry
AwardedBy
American Chemical Society
Role
Principal Investigator
Start Date
January 01, 2014
End Date
August 31, 2016
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Publications:

Direct and Selective 3-Amidation of Indoles Using Electrophilic N-[(Benzenesulfonyl)oxy]amides.

Selective C-H amidation of 1H-indoles at the C3 position is reported as a direct entry to biologically important 3-aminoindoles. This transformation is achieved using novel N-[(benzenesulfonyl)oxy]amides as electrophilic nitrogen agents in the presence of ZnCl2. Interestingly, analogous reactions in the absence of ZnCl2 resulted in the formation of indole aminal products.

Authors
Ortiz, GX; Hemric, BN; Wang, Q
MLA Citation
Ortiz, GX, Hemric, BN, and Wang, Q. "Direct and Selective 3-Amidation of Indoles Using Electrophilic N-[(Benzenesulfonyl)oxy]amides." Organic letters 19.6 (March 10, 2017): 1314-1317.
PMID
28281340
Source
epmc
Published In
Organic Letters
Volume
19
Issue
6
Publish Date
2017
Start Page
1314
End Page
1317
DOI
10.1021/acs.orglett.7b00358

Emerging Developments Using Nitrogen-Heteroatom Bonds as Amination Reagents in the Synthesis of Aminoarenes.

Aminoarenes constitute valuable building blocks in organic synthesis and an essential skeleton ubiquitously found in ligands, agrochemicals, and pharmaceuticals. This Synopsis presents recent amination methods using nitrogen-heteroatom bonds as a powerful and versatile platform to rapidly synthesize diverse aminoarenes, with a focus on aryne amino functionalization and transition-metal-catalyzed arene C-H amination.

Authors
Hendrick, CE; Wang, Q
MLA Citation
Hendrick, CE, and Wang, Q. "Emerging Developments Using Nitrogen-Heteroatom Bonds as Amination Reagents in the Synthesis of Aminoarenes." The Journal of organic chemistry 82.2 (January 6, 2017): 839-847.
PMID
28058838
Source
epmc
Published In
The Journal of Organic Chemistry
Volume
82
Issue
2
Publish Date
2017
Start Page
839
End Page
847
DOI
10.1021/acs.joc.6b02792

Arylation, Vinylation, and Alkynylation of Electron-Deficient (Hetero)arenes Using Iodonium Salts.

Arylation, vinylation, and alkynylation of electron-deficient arenes and heteroarenes have been achieved by chemoselective C-H zincation followed by copper-catalyzed coupling reactions using iodonium salts. This approach offers a direct and general access to a wide scope of (hetero)biaryls as well as alkenylated and alkynylated heteroarenes under mild conditions. It is particularly useful and valuable for the rapid and modular synthesis of diverse (hetero)aryl compounds, as demonstrated in the synthesis of transient receptor potential vanilloid 1 (TRPV1) antagonists and angiotensin II receptor type 1 (AT1 receptor) antagonists.

Authors
Liu, C; Wang, Q
MLA Citation
Liu, C, and Wang, Q. "Arylation, Vinylation, and Alkynylation of Electron-Deficient (Hetero)arenes Using Iodonium Salts." Organic letters (September 8, 2016).
PMID
27607758
Source
epmc
Published In
Organic Letters
Publish Date
2016

Copper-Catalyzed Amino Lactonization and Amino Oxygenation of Alkenes Using O-Benzoylhydroxylamines.

A copper-catalyzed amino lactonization of unsaturated carboxylic acids has been achieved as well as the analogous intermolecular three-component amino oxygenation of olefins. The transformation features mild conditions and a remarkably broad substrate scope, offering a novel and efficient approach to construct a wide range of amino lactones as well as 1,2-amino alcohol derivatives. Mechanistic studies suggest that the reaction proceeds via a distinctive O-benzoylhydroxylamine-promoted electrophilic amination of alkenes.

Authors
Hemric, BN; Shen, K; Wang, Q
MLA Citation
Hemric, BN, Shen, K, and Wang, Q. "Copper-Catalyzed Amino Lactonization and Amino Oxygenation of Alkenes Using O-Benzoylhydroxylamines." Journal of the American Chemical Society 138.18 (May 2016): 5813-5816.
PMID
27114046
Source
epmc
Published In
Journal of the American Chemical Society
Volume
138
Issue
18
Publish Date
2016
Start Page
5813
End Page
5816
DOI
10.1021/jacs.6b02840

Direct and cost-efficient hyperpolarization of long-lived nuclear spin states on universal (15)N2-diazirine molecular tags.

Conventional magnetic resonance (MR) faces serious sensitivity limitations which can be overcome by hyperpolarization methods, but the most common method (dynamic nuclear polarization) is complex and expensive, and applications are limited by short spin lifetimes (typically seconds) of biologically relevant molecules. We use a recently developed method, SABRE-SHEATH, to directly hyperpolarize (15)N2 magnetization and long-lived (15)N2 singlet spin order, with signal decay time constants of 5.8 and 23 minutes, respectively. We find >10,000-fold enhancements generating detectable nuclear MR signals that last for over an hour. (15)N2-diazirines represent a class of particularly promising and versatile molecular tags, and can be incorporated into a wide range of biomolecules without significantly altering molecular function.

Authors
Theis, T; Ortiz, GX; Logan, AWJ; Claytor, KE; Feng, Y; Huhn, WP; Blum, V; Malcolmson, SJ; Chekmenev, EY; Wang, Q; Warren, WS
MLA Citation
Theis, T, Ortiz, GX, Logan, AWJ, Claytor, KE, Feng, Y, Huhn, WP, Blum, V, Malcolmson, SJ, Chekmenev, EY, Wang, Q, and Warren, WS. "Direct and cost-efficient hyperpolarization of long-lived nuclear spin states on universal (15)N2-diazirine molecular tags." Science advances 2.3 (March 25, 2016): e1501438-.
Website
http://hdl.handle.net/10161/11770
PMID
27051867
Source
epmc
Published In
Science Advances
Volume
2
Issue
3
Publish Date
2016
Start Page
e1501438
DOI
10.1126/sciadv.1501438

Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines.

This paper reports a novel approach for the direct and facile synthesis of 1,2-oxyamino moieties via an intermolecular copper-catalyzed oxyamination of olefins. This strategy utilizes O-benzoylhydroxylamines as an electrophilic amine source and carboxylic acids as a nucleophilic oxygen source to achieve a modular difunctionalization of olefins. The reaction proceeded in a regioselective manner with moderate to good yields, exhibiting a broad scope of carboxylic acid, amine, and olefin substrates.

Authors
Hemric, BN; Wang, Q
MLA Citation
Hemric, BN, and Wang, Q. "Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines." Beilstein journal of organic chemistry 12 (January 7, 2016): 22-28. (letter)
PMID
26877805
Source
epmc
Published In
Beilstein journal of organic chemistry
Volume
12
Publish Date
2016
Start Page
22
End Page
28
DOI
10.3762/bjoc.12.4

Copper-catalyzed aminotrifluoromethylation of alkenes: a facile synthesis of CF 3 -containing lactams

Authors
Shen, K; Wang, Q
MLA Citation
Shen, K, and Wang, Q. "Copper-catalyzed aminotrifluoromethylation of alkenes: a facile synthesis of CF 3 -containing lactams." Org. Chem. Front. 3.2 (2016): 222-226.
Source
crossref
Published In
Organic chemistry frontiers : an international journal of organic chemistry / Royal Society of Chemistry
Volume
3
Issue
2
Publish Date
2016
Start Page
222
End Page
226
DOI
10.1039/C5QO00353A

Synthesis of o-Aminophenols via a Formal Insertion Reaction of Arynes into Hydroxyindolinones.

A novel approach toward the synthesis of sterically hindered o-aminophenols has been achieved by a formal aryne insertion into hydroxyindolinones. This transformation offers a rapid and efficient entry to diverse o-aminophenol scaffolds under mild transition-metal-free conditions. The reaction involves the addition of hydroxyindolinones to arynes followed by a chemo- and regioselective [1,3]-rearrangement. Furthermore, the reactions of N-hydroxyindoles and arynes were found to provide the C3-aryl indole products via an alternative [3,3]-rearrangement pathway.

Authors
Chen, Z; Wang, Q
MLA Citation
Chen, Z, and Wang, Q. "Synthesis of o-Aminophenols via a Formal Insertion Reaction of Arynes into Hydroxyindolinones." Organic letters 17.24 (December 8, 2015): 6130-6133.
PMID
26646410
Source
epmc
Published In
Organic Letters
Volume
17
Issue
24
Publish Date
2015
Start Page
6130
End Page
6133
DOI
10.1021/acs.orglett.5b03147

A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2.

Inflammatory status of RPE cells induced by A2E is essential in the development of AMD. Recent research indicated T-cell immunity was involved in the pathological progression of AMD. This study was designed to investigate how A2E suppresses immunoregulatory function of RPE cells in T-cell immunity in vitro.Mouse RPE cells or human ARPE19 cells were stimulated with A2E, and co-cultured with naïve T cells under Th1, Th2, Th17, and regulatory T cell (Treg) polarization conditions. The intracellular cytokines or transcript factors of the induced T-cells subset were detected with flow cytometer and qRT-PCR. The ROS levels were detected, and the factors and possible pathways involved in the A2E-laden RPE cells were analyzed through neutralization antibody of IL-1β and inhibitors of related pathways.The A2E reduced regulatory function of RPE cells in Treg differentiation. The A2E-laden RPE cells promoted polarization of Th1 cells in vitro, but not Th2 or Th17 differentiation. The A2E induced RPE cells to release inflammatory cytokines and ROS, but PGE2 production was inhibited. Through neutralization of IL-1β or inhibition of COX2-PGE2 pathways, A2E-laden RPE cells expressed reduced effect in inducing Th1 cells.The A2E inhibited regulatory function of RPE cells in suppressing Th1 cell immunity in vitro through production of IL-1β and inhibition of PGE2. Our data indicate that A2E could suppress immunoregulatory function of RPE cells and adaptive immunity might play a role in the immune pathogenesis of AMD.

Authors
Shi, Q; Wang, Q; Li, J; Zhou, X; Fan, H; Wang, F; Liu, H; Sun, X; Sun, X
MLA Citation
Shi, Q, Wang, Q, Li, J, Zhou, X, Fan, H, Wang, F, Liu, H, Sun, X, and Sun, X. "A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2." Investigative ophthalmology & visual science 56.13 (December 2015): 7728-7738.
PMID
26641550
Source
epmc
Published In
Investigative Ophthalmology and Visual Science
Volume
56
Issue
13
Publish Date
2015
Start Page
7728
End Page
7738
DOI
10.1167/iovs.15-17677

Synthesis of ortho-haloaminoarenes by aryne insertion of nitrogen-halide bonds.

A rapid and general access to ortho-haloaminoarenes has been developed by aryne insertion into N-chloramine, N-bromoamine, and N-iodoamine bonds via two complementary protocols harnessing fluoride-promoted 1,2-elimination of ortho-trimethylsilyl aryltriflates. Typically, electron-deficient N-chloramines effectively react with aryne intermediates generated at elevated temperature with CsF, while less stable N-haloamines are found more efficient under milder, TBAF-mediated aryne formation at room temperature. Both protocols demonstrate a good level of regioselectivity and functional group tolerance. Efforts to elucidate the mechanism of N-X insertion are also discussed. The practical value of this transformation is highlighted by rapid synthesis of novel analogues of the antipsychotic cariprazine.

Authors
Hendrick, CE; Wang, Q
MLA Citation
Hendrick, CE, and Wang, Q. "Synthesis of ortho-haloaminoarenes by aryne insertion of nitrogen-halide bonds." The Journal of organic chemistry 80.2 (January 2015): 1059-1069.
PMID
25495648
Source
epmc
Published In
The Journal of Organic Chemistry
Volume
80
Issue
2
Publish Date
2015
Start Page
1059
End Page
1069
DOI
10.1021/jo502541t

Copper-catalyzed diamination of unactivated alkenes with hydroxylamines

Authors
Shen, K; Wang, Q
MLA Citation
Shen, K, and Wang, Q. "Copper-catalyzed diamination of unactivated alkenes with hydroxylamines." Chem. Sci. 6.7 (2015): 4279-4283.
Source
crossref
Published In
Chemical Science
Volume
6
Issue
7
Publish Date
2015
Start Page
4279
End Page
4283
DOI
10.1039/C5SC00897B

Copper-Catalyzed Electrophilic Amination of Heteroaromatic and Aromatic C−H Bonds via TMPZnCl•LiCl Mediated Metalation

Authors
McDonald, S
MLA Citation
McDonald, S. "Copper-Catalyzed Electrophilic Amination of Heteroaromatic and Aromatic C−H Bonds via TMPZnCl•LiCl Mediated Metalation." Organic Syntheses 92 (2015): 356-372.
Source
crossref
Volume
92
Publish Date
2015
Start Page
356
End Page
372
DOI
10.15227/orgsyn.092.0356

α-Amination of Phosphonates: A Direct Synthesis of α-Amino Phosphonic Acids and Their Derivatives

Authors
McDonald, S; Wang, Q
MLA Citation
McDonald, S, and Wang, Q. "α-Amination of Phosphonates: A Direct Synthesis of α-Amino Phosphonic Acids and Their Derivatives." Synlett 25.16 (September 18, 2014): 2233-2238.
Source
crossref
Published In
Synlett
Volume
25
Issue
16
Publish Date
2014
Start Page
2233
End Page
2238
DOI
10.1055/s-0034-1378324

Epithelial-to-mesenchymal transition activates PERK-eIF2α and sensitizes cells to endoplasmic reticulum stress.

Epithelial-to-mesenchymal transition (EMT) promotes both tumor progression and drug resistance, yet few vulnerabilities of this state have been identified. Using selective small molecules as cellular probes, we show that induction of EMT greatly sensitizes cells to agents that perturb endoplasmic reticulum (ER) function. This sensitivity to ER perturbations is caused by the synthesis and secretion of large quantities of extracellular matrix (ECM) proteins by EMT cells. Consistent with their increased secretory output, EMT cells display a branched ER morphology and constitutively activate the PERK-eIF2α axis of the unfolded protein response (UPR). Protein kinase RNA-like ER kinase (PERK) activation is also required for EMT cells to invade and metastasize. In human tumor tissues, EMT gene expression correlates strongly with both ECM and PERK-eIF2α genes, but not with other branches of the UPR. Taken together, our findings identify a novel vulnerability of EMT cells, and demonstrate that the PERK branch of the UPR is required for their malignancy.EMT drives tumor metastasis and drug resistance, highlighting the need for therapies that target this malignant subpopulation. Our findings identify a previously unrecognized vulnerability of cancer cells that have undergone an EMT: sensitivity to ER stress. We also find that PERK-eIF2α signaling, which is required to maintain ER homeostasis, is also indispensable for EMT cells to invade and metastasize.

Authors
Feng, Y-X; Sokol, ES; Del Vecchio, CA; Sanduja, S; Claessen, JHL; Proia, TA; Jin, DX; Reinhardt, F; Ploegh, HL; Wang, Q; Gupta, PB
MLA Citation
Feng, Y-X, Sokol, ES, Del Vecchio, CA, Sanduja, S, Claessen, JHL, Proia, TA, Jin, DX, Reinhardt, F, Ploegh, HL, Wang, Q, and Gupta, PB. "Epithelial-to-mesenchymal transition activates PERK-eIF2α and sensitizes cells to endoplasmic reticulum stress." Cancer discovery 4.6 (June 2014): 702-715.
PMID
24705811
Source
epmc
Published In
Cancer Discovery
Volume
4
Issue
6
Publish Date
2014
Start Page
702
End Page
715
DOI
10.1158/2159-8290.cd-13-0945

Copper-catalyzed electrophilic amination of heteroarenes and arenes by C-H zincation.

Direct amination of heteroarenes and arenes has been achieved in a one-pot CH zincation/copper-catalyzed electrophilic amination procedure. This amination method provides an efficient and rapid approach to access a diverse range of heteroaromatic and aromatic amines including those previously inaccessible using CH amination methods. The mild reaction conditions and good functional-group compatibility demonstrate its great potential for the synthesis of important and complex amines.

Authors
McDonald, SL; Hendrick, CE; Wang, Q
MLA Citation
McDonald, SL, Hendrick, CE, and Wang, Q. "Copper-catalyzed electrophilic amination of heteroarenes and arenes by C-H zincation." Angewandte Chemie (International ed. in English) 53.18 (April 2014): 4667-4670.
PMID
24668522
Source
epmc
Published In
Angewandte Chemie International Edition
Volume
53
Issue
18
Publish Date
2014
Start Page
4667
End Page
4670
DOI
10.1002/anie.201311029

Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production.

Reversible acetylation of α-tubulin is an evolutionarily conserved modification in microtubule networks. Despite its prevalence, the physiological function and regulation of microtubule acetylation remain poorly understood. Here we report that macrophages challenged by bacterial lipopolysaccharides (LPS) undergo extensive microtubule acetylation. Suppression of LPS-induced microtubule acetylation by inactivating the tubulin acetyltransferase, MEC17, profoundly inhibits the induction of anti-inflammatory interleukin-10 (IL-10), a phenotype effectively reversed by an acetylation-mimicking α-tubulin mutant. Conversely, elevating microtubule acetylation by inhibiting the tubulin deacetylase, HDAC6, or stabilizing microtubules via Taxol stimulates IL-10 hyper-induction. Supporting the anti-inflammatory function of microtubule acetylation, HDAC6 inhibition significantly protects mice from LPS toxicity. In HDAC6-deficient macrophages challenged by LPS, p38 kinase signalling becomes selectively amplified, leading to SP1-dependent IL-10 transcription. Remarkably, the augmented p38 signalling is suppressed by MEC17 inactivation. Our findings identify reversible microtubule acetylation as a kinase signalling modulator and a key component in the inflammatory response.

Authors
Wang, B; Rao, Y-H; Inoue, M; Hao, R; Lai, C-H; Chen, D; McDonald, SL; Choi, M-C; Wang, Q; Shinohara, ML; Yao, T-P
MLA Citation
Wang, B, Rao, Y-H, Inoue, M, Hao, R, Lai, C-H, Chen, D, McDonald, SL, Choi, M-C, Wang, Q, Shinohara, ML, and Yao, T-P. "Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production." Nature communications 5 (March 17, 2014): 3479-.
PMID
24632940
Source
epmc
Published In
Nature Communications
Volume
5
Publish Date
2014
Start Page
3479
DOI
10.1038/ncomms4479

Selective α-amination and α-acylation of esters and amides via dual reactivity of O-acylhydroxylamines toward zinc enolates.

Selective α-amination and α-acylation of esters and amides have been developed, employing O-acylhydroxylamines as a dually reactive aminating and acylating reagent. Treatment of zinc enolates with O-acylhydroxylamines provides solely 1,3-dicarbonyl compounds under mild conditions. Introduction of a copper catalyst into the system shifts the reactivity entirely, yielding α-amination products exclusively.

Authors
McDonald, SL; Wang, Q
MLA Citation
McDonald, SL, and Wang, Q. "Selective α-amination and α-acylation of esters and amides via dual reactivity of O-acylhydroxylamines toward zinc enolates." Chemical communications (Cambridge, England) 50.19 (March 2014): 2535-2538.
PMID
24463701
Source
epmc
Published In
Chemical Communications
Volume
50
Issue
19
Publish Date
2014
Start Page
2535
End Page
2538
DOI
10.1039/c3cc49296f

Copper-catalyzed α-amination of phosphonates and phosphine oxides: a direct approach to α-amino phosphonic acids and derivatives.

A direct approach to important α-amino phosphonic acids and its derivatives has been developed by using copper-catalyzed electrophilic amination of α-phosphonate zincates with O-acyl hydroxylamines. This amination provides the first example of CN bond formation which directly introduces acyclic and cyclic amines to the α-position of phosphonates in one step. The reaction is readily promoted at room temperature with as little as 0.5 mol % of catalyst, and demonstrates high efficiency on a broad substrate scope.

Authors
McDonald, SL; Wang, Q
MLA Citation
McDonald, SL, and Wang, Q. "Copper-catalyzed α-amination of phosphonates and phosphine oxides: a direct approach to α-amino phosphonic acids and derivatives." Angewandte Chemie (International ed. in English) 53.7 (February 2014): 1867-1871.
PMID
24474326
Source
epmc
Published In
Angewandte Chemie International Edition
Volume
53
Issue
7
Publish Date
2014
Start Page
1867
End Page
1871
DOI
10.1002/anie.201308890

One-pot synthesis of 3-azido- and 3-aminopiperidines by intramolecular cyclization of unsaturated amines.

A highly efficient one-pot synthesis of 3-azidopiperidines has been achieved by an intramolecular cyclization of unsaturated amines that allows for the nucleophilic installation of an azide moiety. This method unlocks the versatile employment of the azide functionality in the preparation and biological studies of piperidine-containing structures. This strategy has been expanded for the direct incorporation of a variety of nitrogen nucleophiles, and thus it provides a rapid and modular synthesis of 3-amino and 3-amidopiperidines of important pharmaceutical and biological relevance. Particularly noteworthy is that the regioselectivity of this transformation enables the formation of the anti-Markovnikov-type adduct, complementing Markovnikov-based olefin amino functionalization methods.

Authors
Ortiz, GX; Kang, B; Wang, Q
MLA Citation
Ortiz, GX, Kang, B, and Wang, Q. "One-pot synthesis of 3-azido- and 3-aminopiperidines by intramolecular cyclization of unsaturated amines." J Org Chem 79.2 (January 17, 2014): 571-581.
PMID
24359462
Source
pubmed
Published In
The Journal of Organic Chemistry
Volume
79
Issue
2
Publish Date
2014
Start Page
571
End Page
581
DOI
10.1021/jo4022666

Insertion of arynes into N-halo bonds: a direct approach to o-haloaminoarenes.

A new approach to access o-haloaminoarenes has been achieved by insertion of arynes into a nitrogen-halide bond (N-X). This transition-metal-free transformation displays a broad substrate scope of arynes, good compatibility with functional groups, and high regioselectivity. Representative transformations of the o-haloaminoarenes are described to highlight their utility for rapid access to diversely functionalized aminoarene derivatives.

Authors
Hendrick, CE; McDonald, SL; Wang, Q
MLA Citation
Hendrick, CE, McDonald, SL, and Wang, Q. "Insertion of arynes into N-halo bonds: a direct approach to o-haloaminoarenes." Org Lett 15.13 (July 5, 2013): 3444-3447.
PMID
23796022
Source
pubmed
Published In
Organic Letters
Volume
15
Issue
13
Publish Date
2013
Start Page
3444
End Page
3447
DOI
10.1021/ol401518c

Storage of hydrogen spin polarization in long-lived 13C2 singlet order and implications for hyperpolarized magnetic resonance imaging.

Hyperpolarized magnetic resonance imaging (MRI) is a powerful technique enabling real-time monitoring of metabolites at concentration levels not accessible by standard MRI techniques. A considerable challenge this technique faces is the T1 decay of the hyperpolarization upon injection into the system under study. Here we show that A(n)A'(n)XX' spin systems such as (13)C2-1,2-diphenylacetylene ((13)C2-DPA) sustain long-lived polarization for both (13)C and (1)H spins with decay constants of almost 4.5 min at high magnetic fields of up to 16.44 T without spin-locking; the T1 of proton polarization is only 3.8 s. Therefore, storage of the proton polarization in a (13)C2-singlet state causes a 69-fold extension of the spin lifetime. Notably, this extension is demonstrated with proton-only pulse sequences, which can be readily implemented on standard clinical scanners.

Authors
Feng, Y; Theis, T; Liang, X; Wang, Q; Zhou, P; Warren, WS
MLA Citation
Feng, Y, Theis, T, Liang, X, Wang, Q, Zhou, P, and Warren, WS. "Storage of hydrogen spin polarization in long-lived 13C2 singlet order and implications for hyperpolarized magnetic resonance imaging." Journal of the American Chemical Society 135.26 (July 2013): 9632-9635.
PMID
23781874
Source
epmc
Published In
Journal of the American Chemical Society
Volume
135
Issue
26
Publish Date
2013
Start Page
9632
End Page
9635
DOI
10.1021/ja404936p

Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells.

The histone methyltransferase G9a is overexpressed in a variety of cancer types, including pancreatic adenocarcinoma, and promotes tumor invasiveness and metastasis. We recently reported the discovery of BRD4770, a small-molecule inhibitor of G9a that induces senescence in PANC-1 cells. We observed that the cytotoxic effects of BRD4770 were dependent on genetic background, with cell lines lacking functional p53 being relatively resistant to compound treatment. To understand the mechanism of genetic selectivity, we used two complementary screening approaches to identify enhancers of BRD4770. The natural product and putative BH3 mimetic gossypol enhanced the cytotoxicity of BRD4770 in a synergistic manner in p53-mutant PANC-1 cells but not in immortalized non-tumorigenic pancreatic cells. The combination of gossypol and BRD4770 increased LC3-II levels and the autophagosome number in PANC-1 cells, and the compound combination appears to act in a BNIP3 (B-cell lymphoma 2 19-kDa interacting protein)-dependent manner, suggesting that these compounds act together to induce autophagy-related cell death in pancreatic cancer cells.

Authors
Yuan, Y; Tang, AJ; Castoreno, AB; Kuo, S-Y; Wang, Q; Kuballa, P; Xavier, R; Shamji, AF; Schreiber, SL; Wagner, BK
MLA Citation
Yuan, Y, Tang, AJ, Castoreno, AB, Kuo, S-Y, Wang, Q, Kuballa, P, Xavier, R, Shamji, AF, Schreiber, SL, and Wagner, BK. "Gossypol and an HMT G9a inhibitor act in synergy to induce cell death in pancreatic cancer cells." Cell death & disease 4 (June 27, 2013): e690-.
PMID
23807219
Source
epmc
Published In
Cell Death and Disease
Volume
4
Publish Date
2013
Start Page
e690
DOI
10.1038/cddis.2013.191

An efficient synthesis of fluorinated azaheterocycles by aminocyclization of alkenes.

A general and efficient approach to important fluorinated azaheterocycles has been developed by incorporating nucleophilic fluorination into alkene difunctionalization. This intramolecular aminofluorination transformation of alkenes has been achieved via the aminocyclization of reactive unsaturated N-iodoamines, which can be generated in situ from either unsaturated N-chloramines or their amine precursors in a one-pot protocol.

Authors
Huang, H-T; Lacy, TC; Błachut, B; Ortiz, GX; Wang, Q
MLA Citation
Huang, H-T, Lacy, TC, Błachut, B, Ortiz, GX, and Wang, Q. "An efficient synthesis of fluorinated azaheterocycles by aminocyclization of alkenes." Org Lett 15.8 (April 19, 2013): 1818-1821.
PMID
23544433
Source
pubmed
Published In
Organic Letters
Volume
15
Issue
8
Publish Date
2013
Start Page
1818
End Page
1821
DOI
10.1021/ol4003866

A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma

Post-translational modifications of histones alter chromatin structure and play key roles in gene expression and specification of cell states. Small molecules that target chromatin-modifying enzymes selectively are useful as probes and have promise as therapeutics, although very few are currently available. G9a (also named euchromatin histone methyltransferase 2 (EHMT2)) catalyzes methylation of lysine 9 on histone H3 (H3K9), a modification linked to aberrant silencing of tumor-suppressor genes, among others. Here, we report the discovery of a novel histone methyltransferase inhibitor, BRD4770. This compound reduced cellular levels of di- and trimethylated H3K9 without inducing apoptosis, induced senescence, and inhibited both anchorage-dependent and -independent proliferation in the pancreatic cancer cell line PANC-1. ATM-pathway activation, caused by either genetic or small-molecule inhibition of G9a, may mediate BRD4770-induced cell senescence. BRD4770 may be a useful tool to study G9a and its role in senescence and cancer cell biology. © 2012 American Chemical Society.

Authors
Yuan, Y; Wang, Q; Paulk, J; Kubicek, S; Kemp, MM; Adams, DJ; Shamji, AF; Wagner, BK; Schreiber, SL
MLA Citation
Yuan, Y, Wang, Q, Paulk, J, Kubicek, S, Kemp, MM, Adams, DJ, Shamji, AF, Wagner, BK, and Schreiber, SL. "A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma." ACS Chemical Biology 7.7 (2012): 1152-1157.
PMID
22536950
Source
scival
Published In
ACS Chemical Biology
Volume
7
Issue
7
Publish Date
2012
Start Page
1152
End Page
1157
DOI
10.1021/cb300139y

A novel HDAC inhibitor with a hydroxy-pyrimidine scaffold

Histone deacetylases (HDACs) are enzymes involved in many important biological functions. They have been linked to a variety of cancers, psychiatric disorders, and other diseases. Since small molecules can serve as probes to study the relevant biological roles of HDACs, novel scaffolds are necessary to develop more efficient, selective drug candidates. Screening libraries of molecules may yield structurally diverse probes that bind these enzymes and modulate their functions in cells. Here we report a small molecule with a novel hydroxy-pyrimidine scaffold that inhibits multiple HDAC enzymes and modulates acetylation levels in cells. Analogs were synthesized in an effort to evaluate structure-activity relationships. © 2011 Elsevier Ltd. All rights reserved.

Authors
Kemp, MM; Wang, Q; Fuller, JH; West, N; Martinez, NM; Morse, EM; Weïwer, M; Schreiber, SL; Bradner, JE; Koehler, AN
MLA Citation
Kemp, MM, Wang, Q, Fuller, JH, West, N, Martinez, NM, Morse, EM, Weïwer, M, Schreiber, SL, Bradner, JE, and Koehler, AN. "A novel HDAC inhibitor with a hydroxy-pyrimidine scaffold." Bioorganic and Medicinal Chemistry Letters 21.14 (2011): 4164-4169.
PMID
21696956
Source
scival
Published In
Bioorganic & Medicinal Chemistry Letters
Volume
21
Issue
14
Publish Date
2011
Start Page
4164
End Page
4169
DOI
10.1016/j.bmcl.2011.05.098

Copper-mediated amidation of heterocyclic and aromatic C-H bonds

A copper-mediated aerobic coupling reaction enables direct amidation of heterocycles or aromatics having weakly acidic C-H bonds with a variety of nitrogen nucleophiles. These reactions provide efficient access to many biologically important skeletons, including ones with the potential to serve as inhibitors of HMTs. © 2009 American Chemical Society.

Authors
Wang, Q; Schreiber, SL
MLA Citation
Wang, Q, and Schreiber, SL. "Copper-mediated amidation of heterocyclic and aromatic C-H bonds." Organic Letters 11.22 (2009): 5178-5180.
PMID
19860425
Source
scival
Published In
Organic Letters
Volume
11
Issue
22
Publish Date
2009
Start Page
5178
End Page
5180
DOI
10.1021/ol902079g

“A robust platform for the synthesis of new tetracycline antibiotics

Authors
Sun, C; Wang, Q; Brubaker, JD; Wright, PM; Lerner, CD; Noson, K; Charest, M; Siegel, DR; Wang, Y-M; Myers, AG
MLA Citation
Sun, C, Wang, Q, Brubaker, JD, Wright, PM, Lerner, CD, Noson, K, Charest, M, Siegel, DR, Wang, Y-M, and Myers, AG. "“A robust platform for the synthesis of new tetracycline antibiotics." J. Am. Chem. Soc 130 (2008): 17913-. (Academic Article)
PMID
19053822
Source
manual
Published In
J. Am. Chem. Soc
Issue
130
Publish Date
2008
Start Page
17913

Synthesis of the tetracyclic framework of the erythrina alkaloids using a [4 + 2]-cycloaddition/Rh(I)-catalyzed cascade of 2-imidofurans

Several 2-imido substituted furans were found to undergo a rapid intramolecular [4 + 2]-cycloaddition to deliver oxabicyclo adducts in good to excellent yields. By using a Rh(I)-catalyzed ring opening of the resulting oxabicyclic adduct, it was possible to prepare several highly functionalized tetrahydro-1H-indol-2(3H)-one derivatives which were then used to prepare several erythrina alkaloids. By taking advantage of the Rh(I)-catalyzed reaction, it was possible to convert tert-butyl 3-oxo-5-carbomethoxy-10-oxa-2- azatricyclo[5.2.1.01,5]dec-8-ene-2-carboxylate into the ring opened boronate by reaction with phenylboronic acid. Treatment of the boronate with pinacol/acetic acid afforded the corresponding diol which was used in a successful synthesis of racemic 3-demethoxyerythratidinone. During the course of these studies, several novel rearrangement reactions were encountered while attempting to induce an acid-initiated Pictet Spengler cyclization of a key lactam intermediate. The IMDAF/Rh(I)-catalyzed ring opening cascade sequence was also applied to the total synthesis of (±)-erysotramidine as well as the lycorine type alkaloid (±)-epi-zephyranthine. © 2006 American Chemical Society.

Authors
Padwa, A; Wang, Q
MLA Citation
Padwa, A, and Wang, Q. "Synthesis of the tetracyclic framework of the erythrina alkaloids using a [4 + 2]-cycloaddition/Rh(I)-catalyzed cascade of 2-imidofurans." Journal of Organic Chemistry 71.19 (2006): 7391-7402.
PMID
16958534
Source
scival
Published In
The Journal of Organic Chemistry
Volume
71
Issue
19
Publish Date
2006
Start Page
7391
End Page
7402
DOI
10.1021/jo061269p

Synthesis of the Erythrina alkaloid 3-demethoxyerythratidinone. Novel acid-induced rearrangements of its precursors

A new strategy for the synthesis of 3-demethoxyerythratidinone has been developed and is based on an extraordinarily facile intramolecular Diels-Alder reaction of a 2-imido-substituted furan. During the course of the synthesis, several novel acid-induced rearrangement reactions were encountered. © 2006 American Chemical Society.

Authors
Wang, Q; Padwa, A
MLA Citation
Wang, Q, and Padwa, A. "Synthesis of the Erythrina alkaloid 3-demethoxyerythratidinone. Novel acid-induced rearrangements of its precursors." Organic Letters 8.4 (2006): 601-604.
PMID
16468721
Source
scival
Published In
Organic Letters
Volume
8
Issue
4
Publish Date
2006
Start Page
601
End Page
604
DOI
10.1021/ol0527330

Rhodium(I)-catalyzed nucleophilic ring-opening reactions of oxabicyclo adducts derived from the [4 + 2]-cycloaddition of 2-imido-substituted furans

A series of 2-imido-substituted furans containing tethered unsaturation were prepared by the addition of the lithium carbamate of furan-2-ylcarbamic acid tert-butyl ester to a solution of the mixed anhydride of an appropriately substituted 3-butenoic acid. The initially formed imido furans undergo a rapid intramolecular [4 + 2]-cycloaddition at room temperature to deliver the Diels-Alder cycloadducts in good to excellent yield. Isolation of the highly labile oxabicyclic adduct is believed to be a consequence of the lower reaction temperatures employed as well as the presence of the extra carbonyl group, which diminishes the basicity of the nitrogen atom, thereby retarding the ring cleavage/rearrangement reaction generally encountered with related systems. By using a Rh(I)-catalyzed ring opening of the oxabicyclic adduct with various nucleophilic reagents, it was possible to prepare highly functionalized hexahydro-1H-indol-2(3H)-one derivatives in good yield. The major stereoisomer obtained possesses a π-relationship between the nucleophile and hydroxyl group in the ring-opened product. The stereochemistry was unequivocally established by X-ray crystallographic analysis. Coordination of Rh(I) to the alkenyl π-bond followed by a nitrogen-assisted cleavage of the carbon-oxygen bond occurs to furnish a π-allyl rhodium-(III) species. Addition of the nucleophile then occurs from the least hindered terminus of the resulting π-allyl rhodium(III) complex. Proton exchange followed by rhodium(I) decomplexation ultimately leads to the cis-diastereomer. © 2006 American Chemical Society.

Authors
Padwa, A; Wang, Q
MLA Citation
Padwa, A, and Wang, Q. "Rhodium(I)-catalyzed nucleophilic ring-opening reactions of oxabicyclo adducts derived from the [4 + 2]-cycloaddition of 2-imido-substituted furans." Journal of Organic Chemistry 71.8 (2006): 3210-3220.
PMID
16599620
Source
scival
Published In
The Journal of Organic Chemistry
Volume
71
Issue
8
Publish Date
2006
Start Page
3210
End Page
3220
DOI
10.1021/jo060238r

Additive Pummerer reaction of heteroaromatic sulfilimines with carbon nucleophiles

The additive Pummerer reaction of several heteroaromatic sulfilimines has been investigated. The overall process involves the reaction of the sulfilimine with TFAA to produce a transient N-tosyl-N-trifluoroacetyl sulfonium ion. Nucleophilic attack at the adjacent vinyl carbon results in the ejection of the sulfonamide group and the resulting thionium ion loses a proton to give the observed product. © 2005 Elsevier Ltd. All rights reserved.

Authors
Padwa, A; Nara, S; Wang, Q
MLA Citation
Padwa, A, Nara, S, and Wang, Q. "Additive Pummerer reaction of heteroaromatic sulfilimines with carbon nucleophiles." Tetrahedron Letters 47.4 (2006): 595-597.
Source
scival
Published In
Tetrahedron Letters
Volume
47
Issue
4
Publish Date
2006
Start Page
595
End Page
597
DOI
10.1016/j.tetlet.2005.11.026

Dichloroketene-induced cyclizations of vinyl sulfilimines: Application of the method in the synthesis of (±)-desoxyeseroline

The reactions of several aryl-, furanyl-, and vinyl-substituted sulfilimines with dichloroketene proceeded at 25 °C to yield thioalkyl-substituted γ-lactams. The overall process involves nucleophilic addition of the nitrogen atom of the sulfilimine onto the highly electrophilic dichloroketene to first generate a zwitterionic intermediate. A subsequent [3,3]-sigmatropic rearrangement is followed by intramolecular trapping of the Pummerer cation by the amido anion to furnish the observed γ-lactam product. Incorporation of donor groups on the aromatic ring of the sulfonyl functionality had little effect when aryl-substituted sulfilimines were used but exhibited a major effect on the efficiency of the reaction with furanyl-substituted systems. The placement of an electron donor group (i.e., OMe) on the sulfonyl aryl group enhances the nucleophilicity of the amido anion contained within the sulfonium ion intermediate and facilitates the rate of the 3,3-sigmatropic rearrangement. Styryl-substituted sulfilimines cyclize in a stereospecific manner and produce a 3:2-mixture of γ-lactams and the isomeric imino-lactone system. The heavily functionalized γ-lactams are easily converted to a variety of nitrogen containing substrates. The vinyl sulfilimine cyclization method was applied to the total synthesis of the Calabar alkaloid (±)-desoxyeseroline. © 2005 American Chemical Society.

Authors
Padwa, A; Nara, S; Wang, Q
MLA Citation
Padwa, A, Nara, S, and Wang, Q. "Dichloroketene-induced cyclizations of vinyl sulfilimines: Application of the method in the synthesis of (±)-desoxyeseroline." Journal of Organic Chemistry 70.21 (2005): 8538-8549.
PMID
16209605
Source
scival
Published In
The Journal of Organic Chemistry
Volume
70
Issue
21
Publish Date
2005
Start Page
8538
End Page
8549
DOI
10.1021/jo051550o

A new synthesis of γ-lactams based on the reaction of vinyl sulfilimines with dichloroketene

(Chemical Equation Presented) The reactions of several aryl-, furanyl-, and vinyl substituted sulfilimines with dichloroketene proceeded at 25°C to yield thioalkyl substituted γ-lactams which, in turn, were converted to a variety of nitrogen-containing substrates. © 2005 American Chemical Society.

Authors
Wang, Q; Nara, S; Padwa, A
MLA Citation
Wang, Q, Nara, S, and Padwa, A. "A new synthesis of γ-lactams based on the reaction of vinyl sulfilimines with dichloroketene." Organic Letters 7.5 (2005): 839-841.
PMID
15727454
Source
scival
Published In
Organic Letters
Volume
7
Issue
5
Publish Date
2005
Start Page
839
End Page
841
DOI
10.1021/ol047453j

Rh(I)-catalyzed ring opening of an IMDAF-derived oxabicyclo cycloadduct as the key step in the synthesis of (±)-epi-zephyranthine

A new strategy for epi-zephyranthine has been developed that is based in part on an extraordinarily facile intramolecular Diels-Alder reaction of a 2-imido-substituted furan. By using a Rh(I)-catalyzed ring opening of the resulting oxabicyclic adduct, the cis-diol stereochemistry of epi-zephyranthine was established.

Authors
Wang, Q; Padwa, A
MLA Citation
Wang, Q, and Padwa, A. "Rh(I)-catalyzed ring opening of an IMDAF-derived oxabicyclo cycloadduct as the key step in the synthesis of (±)-epi-zephyranthine." Organic Letters 6.13 (2004): 2189-2192.
PMID
15200317
Source
scival
Published In
Organic Letters
Volume
6
Issue
13
Publish Date
2004
Start Page
2189
End Page
2192
DOI
10.1021/ol049348f

A new strategy toward indole alkaloids involving an intramolecular cycloaddition/rearrangement cascade

The intramolecular Diels-Alder reaction between an amidofuran moiety tethered onto an indole component was examined as a strategy for the synthesis of Aspidosperma alkaloids. Furanyl carbamate 23 was acylated using the mixed anhydride 26 to provide amidofuran 22 in 68% yield. Further N-acylation of this indole furnished 27 in 88% yield. Cyclization precursors were prepared by removing the carbamate moiety followed by N-alkylation with the appropriate alkyl halides. Large substituent groups on the amido nitrogen atom causes the reactive s-trans conformation of the amidofuran to be more highly populated, thereby facilitating the Diels-Alder cycloaddition. The reaction requires the presence of an electron-withdrawing substituent on the indole nitrogen in order for the cycloaddition to proceed. Treatment of N-allyl-bromoenamide 48 with n-Bu3SnH/ AIBN preferentially led to the 6-endo trig cyclization product 50, with the best yield (91%) being obtained under high dilution conditions. The initially generated cyclohexenyl radical derived from 48 produces the pentacyclic heterocycle 50 by either a direct 6-endo trig cyclization or, alternatively, by a vinyl radical rearrangement pathway.

Authors
Padwa, A; Brodney, MA; Lynch, SM; Rashatasakhon, P; Wang, Q; Zhang, H
MLA Citation
Padwa, A, Brodney, MA, Lynch, SM, Rashatasakhon, P, Wang, Q, and Zhang, H. "A new strategy toward indole alkaloids involving an intramolecular cycloaddition/rearrangement cascade." Journal of Organic Chemistry 69.11 (2004): 3735-3745.
PMID
15153003
Source
scival
Published In
Journal of Organic Chemistry
Volume
69
Issue
11
Publish Date
2004
Start Page
3735
End Page
3745

Tandem Pummerer/Mannich Cyclization Cascade of α-Sulfinylamides as a Method to Prepare Aza-Heterocycles.

Authors
Padwa, A; Heidelbaugh, TM; Kuethe, JT; McClure, MS; Wang, Q
MLA Citation
Padwa, A, Heidelbaugh, TM, Kuethe, JT, McClure, MS, and Wang, Q. "Tandem Pummerer/Mannich Cyclization Cascade of α-Sulfinylamides as a Method to Prepare Aza-Heterocycles." ChemInform 34.4 (January 28, 2003).
Source
crossref
Published In
ChemInform
Volume
34
Issue
4
Publish Date
2003
DOI
10.1002/chin.200304040

Tandem pummerer/mannich cyclization cascade of α-sulfinylamides as a method to prepare aza-heterocycles

A series of α-sulfinylenamides was conveniently prepared by the condensation of a primary amine with a ketone, followed by reaction of the resulting imine with ethylsulfenylacetyl chloride and subsequent oxidation with sodium periodate. When treated with p-TsOH, cyclization occurred to produce fused isoquinoline lactams by a mechanism that involves an initial Pummerer reaction followed by a subsequent cyclization of the resulting N-acyliminium ion onto the tethered aromatic ring. The isolation of a single diastereomer was rationalized in terms of a Nazarov-type 4π-electrocyclic reaction followed by π-cyclization onto the least hindered side of the N-acyliminium ion. Another method that was used to generate the α-acylthionium ion intermediate involved the reaction of bis(ethylsulfenylacetyl)acetamides with dimethyl(methyl)thiosulfonium tetrafluoroborate (DMTSF). Treatment of several bis-ethylsulfenylenamides with DMTSF delivered novel spiroheterocycles as single diastereomers in good yield by a related process. The convergency and stereochemical control associated with this cascade sequence make it particularly suited for the assembly of natural product scaffolds. Some preliminary studies were directed toward both mesembrine and deethylibophyllidine. When the model Z-enamido sulfoxide 33 was heated with p-TsOH, a 80% yield of tosylate 34 was obtained as a single diastereomer. In this case, the carbocation intermediate derived from cyclization onto the terminal π-bond was trapped with p-TsOH from the least hindered face, opposite the angular carbomethoxy and methyl groups. Related cyclization cascades were also found to occur with systems containing tethered indole rings.

Authors
Padwa, A; Heidelbaugh, TM; Kuethe, JT; McClure, MS; Wang, Q
MLA Citation
Padwa, A, Heidelbaugh, TM, Kuethe, JT, McClure, MS, and Wang, Q. "Tandem pummerer/mannich cyclization cascade of α-sulfinylamides as a method to prepare aza-heterocycles." Journal of Organic Chemistry 67.17 (2002): 5928-5937.
PMID
12182624
Source
scival
Published In
The Journal of Organic Chemistry
Volume
67
Issue
17
Publish Date
2002
Start Page
5928
End Page
5937
DOI
10.1021/jo020083x

DOS-Derived Small-Molecule Probes in Chemical Biology

Authors
Wang, Q; Nicholas, H; Du, L
MLA Citation
Wang, Q, Nicholas, H, and Du, L. "DOS-Derived Small-Molecule Probes in Chemical Biology." Diversity-Oriented Synthesis: Basics and Applications in Organic Synthesis, Drug Discovery, and Chemical Biology. Ed. A Trabocchi. (Chapter)
Source
manual
DOI
10.1002/9781118618110.ch18
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