QingLong Guo

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Name: 郭青龙

Organization: China Pharmaceutical University , China

Department: Department of Chemistry

Title: (PhD)

TOPICS

Organic Chemistry

Chemicals
References

Stereoselective Synthesis of Quaternary Pyrrolidine-2,3-diones and β-Amino Acids

Co-reporter:Nataliia V. Shymanska and Joshua G. Pierce

Organic Letters June 2, 2017 Volume 19(Issue 11) pp:

Publication Date(Web):May 24, 2017

DOI:10.1021/acs.orglett.7b01185

A facile, diastereoselective synthesis of highly substituted pyrrolidine-2,3-diones is reported, along with the one-step conversion of these heterocycles to novel β-amino acids and further functionalized derivatives. This method involves an unusually mild, one-pot, three-component cyclization/allylation followed by a Claisen rearrangement to provide unusual pyrrolidinone products that are densely functionalized and contain an all-carbon quaternary stereocenter. The reported reaction sequence is operationally simple, exquisitely diastereoselective, and provides gram-scale access to valuable heterocyclic scaffolds and β-amino acids not readily accessible via existing approaches.

Direct Access to Highly Functionalized Heterocycles through the Condensation of Cyclic Imines and α-Oxoesters

Co-reporter:Alexander Q. Cusumano, Matthew W. Boudreau, and Joshua G. Pierce

The Journal of Organic Chemistry December 15, 2017 Volume 82(Issue 24) pp:13714-13714

Publication Date(Web):December 5, 2017

DOI:10.1021/acs.joc.7b02572

A facile, gram-scale preparation of 2-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-ones and 2-hydroxy-6,7,8,8a-tetrahydroindolizin-3(5H)-ones from a condensation cyclization of α-oxoesters with five- and six-membered cyclic imines, respectively, is reported. This transformation enables a concise, three-step synthesis of the natural products phenopyrrozin and p-hydroxyphenopyrrozin. Further, biologically relevant scaffolds, such as α-quaternary β-homo prolines and β-lactams, are also prepared in two- to three-steps from the versatile 2-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-one core.

How Cancer Cells Become Resistant to Cationic Lytic Peptides: It’s the Sugar!

Co-reporter:Joshua G. Pierce

Cell Chemical Biology 2017 Volume 24, Issue 2(Volume 24, Issue 2) pp:

Publication Date(Web):16 February 2017

DOI:10.1016/j.chembiol.2017.01.009

In this issue of Cell Chemical Biology, Ishikawa et al. (2017) demonstrate that the loss of cell-surface anionic saccharides can impart resistance toward anticancer peptides. This study provides the first insight into potential resistance mechanisms toward cationic lytic peptides and highlights the important, yet previously unappreciated, role cell-surface glycans can play in cellular resistance mechanisms.

Structure, synthesis and biological properties of the pentacyclic guanidinium alkaloids

Co-reporter:Yunlong Shi, Yasamin Moazami, Joshua G. Pierce

Bioorganic & Medicinal Chemistry 2017 Volume 25, Issue 11(Issue 11) pp:

Publication Date(Web):1 June 2017

DOI:10.1016/j.bmc.2017.03.015

The pentacyclic guanidinium alkaloids (PGAs) are a family of marine natural products that possess a polycyclic guanidine-containing core and a long alkyl chain tethered spermidine-derived tail that is rarely observed in other natural products. These natural products exhibit potent activities on a wide range of organisms and therefore have attracted the attention of many synthetic chemists; however, the structure-activity relationships and mechanisms of action of PGAs remain largely elusive. Herein we summarize the structure, synthesis, toxicity and mechanisms of action of PGAs and highlight their potential as chemical probes and/or therapeutic leads.Download high-res image (78KB)Download full-size image

Stereocontrolled Synthesis of (+)-Plagiogyrin A

Co-reporter:Yunlong Shi and Joshua G. Pierce

Organic Letters 2016 Volume 18(Issue 20) pp:5308-5311

Publication Date(Web):October 3, 2016

DOI:10.1021/acs.orglett.6b02629

Plagiogyrin A (1) was first isolated from the fronds of Plagiogyria matsumureana. Structurally, it features an α-ketoaldehyde functional group in its hemiacetal form, fused in a cis-substituted lactone ring. We have successfully synthesized the skeleton of this natural product by employing a stereocontrolled aldol reaction followed by the installation of the α-ketoaldehyde moiety derived from the mild oxidation of an α-diazoketone. Finally, anhydrous acidic conditions released the protected diol and provided the required cyclized hemiacetal.

Synthesis of the 5,6-Dihydroxymorpholin-3-one Fragment of Monanchocidin A

Co-reporter:Yunlong Shi and Joshua G. Pierce

Organic Letters 2015 Volume 17(Issue 4) pp:968-971

Publication Date(Web):February 2, 2015

DOI:10.1021/acs.orglett.5b00069

Monanchocidin A is a recently isolated pentacyclic guanidinium alkaloid that contains an unusual highly oxidized morpholinone fragment. Herein we report a rapid synthesis of this heterocyclic scaffold and confirm its structure. The key reaction involves an acid promoted hemiketalization/hemiaminalization of an α-hydroxyamide and α-ketoaldehyde that proceeds with exclusive regioselectivity and high diastereoselectivity to form the natural scaffold in moderate to high yield.

Synthesis of 1,4,2-Oxathiazoles via Oxidative Cyclization of Thiohydroximic Acids

Co-reporter:Bérénice C. Lemercier and Joshua G. Pierce

Organic Letters 2015 Volume 17(Issue 18) pp:4542-4545

Publication Date(Web):September 2, 2015

DOI:10.1021/acs.orglett.5b02256

An oxidative formation of 1,4,2-oxathiazoles from readily available thiohydroximic acids is reported. A variety of alkyl, aryl, and heteroaryl substituents are well tolerated for both the thiohydroximic acid and activating fragments, and the reaction has been demonstrated on gram-scale. This reaction represents the only method currently available to prepare a diverse set of oxathiazoles and expands the chemistry of C–H oxidation via appended N–OH functional groups. Finally, we also demonstrate the rapid preparation of a 1,4,2-oxathiazole analog of an anticancer lead molecule.

Synthesis and biological evaluation of a series of fatty acid amides from Echinacea

Co-reporter:Yasamin Moazami, Travis V. Gulledge, Scott M. Laster, Joshua G. Pierce

Bioorganic & Medicinal Chemistry Letters 2015 Volume 25(Issue 16) pp:3091-3094

Publication Date(Web):15 August 2015

DOI:10.1016/j.bmcl.2015.06.024

Alkylamides are lipophilic constituents of Echinacea and possess numerous biological activities. Although significant effort has been focused on the study of crude Echinacea extracts, very little is known regarding the activities of the individual constituents that make up these herbal treatments. Herein we explore the SAR of simple alkylamides found in Echinacea extracts with respect to their ability to decrease the production of the pro-inflammatory mediator TNF-α. Our results have revealed the key structural requirements for activity and provide lead compounds for further investigation of these poorly understood molecules.

Rapid synthesis and antimicrobial activity of novel 4-oxazolidinone heterocycles

Co-reporter:Nataliia V. Shymanska, Il Hwan An, Sebastián Guevara-Zuluaga, Joshua G. Pierce

Bioorganic & Medicinal Chemistry Letters 2015 Volume 25(Issue 21) pp:4887-4889

Publication Date(Web):1 November 2015

DOI:10.1016/j.bmcl.2015.06.003

The synoxazolidinone family of marine natural products bear an unusual 4-oxazolidinone heterocyclic core and promising antimicrobial activity against several strains of pathogenic bacteria. As part of our research program directed at the synthesis and chemical biology of this family of natural products we have developed a one-step method for the generation of variously substituted 4-oxazolidinone scaffolds from readily available materials. These studies revealed the importance of an electron deficient aromatic ring for antimicrobial activity and serve as the basis for future SAR studies around the 4-oxazolidinone core.

Synthesis of Thiazolines by Copper Catalyzed Aminobromination of Thiohydroximic Acids

Co-reporter:Bérénice C. Lemercier and Joshua G. Pierce

Organic Letters 2014 Volume 16(Issue 7) pp:2074-2076

Publication Date(Web):March 19, 2014

DOI:10.1021/ol500588v

A copper catalyzed aminobromination of alkene tethered thiohydroximic acids is described, providing a rapid approach to unnatural thiazoline scaffolds not readily available via existing methods. Moderate to high yields of bromothiazolines are obtained with alkyl- and aryl-substituted thiohydroximic acid building blocks containing mono-, di-, and trisubstituted alkenes. The reaction provides high levels of 5-exo selectivity, and terminally monosubstituted alkenes result in predominant syn-diastereoselectivity.

A Rapid Synthesis of 4-Oxazolidinones: Total Synthesis of SynoxazolidinonesA and B

Co-reporter:Nataliia V. Shymanska;Il Hwan An ; Joshua G. Pierce

Angewandte Chemie International Edition 2014 Volume 53( Issue 21) pp:5401-5404

Publication Date(Web):

DOI:10.1002/anie.201402310

Abstract

A five-step total synthesis of the marine natural product synoxazolidinone A was achieved through a diastereoselective imine acylation/cyclization cascade. Synoxazolidinone B and a series of analogues were also prepared to explore the potential of these 4-oxazolidinone natural products as antimicrobial agents. These studies confirmed the importance of the chlorine substituent for antimicrobial activity and revealed simplified dichloro derivatives that are equally potent against several bacterial strains.

A Rapid Synthesis of 4-Oxazolidinones: Total Synthesis of SynoxazolidinonesA and B

Co-reporter:Nataliia V. Shymanska;Il Hwan An ; Joshua G. Pierce

Angewandte Chemie 2014 Volume 126( Issue 21) pp:5505-5508

Publication Date(Web):

DOI:10.1002/ange.201402310

Abstract

Synthesis of Thiohydroxamic Acids and Thiohydroximic Acid Derivatives

Co-reporter:Bérénice C. Lemercier and Joshua G. Pierce

The Journal of Organic Chemistry 2014 Volume 79(Issue 5) pp:2321-2330

Publication Date(Web):February 20, 2014

DOI:10.1021/jo500080x

An improved and expanded preparation of thiohydroxamic acids is reported along with a one-pot conversion of these compounds to novel thiohydroximic acid derivatives. A variety of aryl, heteroaryl, and alkyl substituents are well tolerated to provide a rapid approach to alkene-functionalized thiohydroximic acids that serve as potentially useful building blocks for organic synthesis.