Yong Qin

Find an error

Name:

Organization: Sichuan University

Department: West China School of Pharmacy

Title:

TOPICS

Polymer

UV Absorbents

Chemicals
References

Studies towards Bioinspired Synthesis of Hetidine-Type C20-Diterpenoid Alkaloids

Co-reporter:Min Zhu;Xiaohuan Li;Xue Song;Zhixiu Wang;Xiaoyu Liu;Hao Song;Dan Zhang;Fengpeng Wang

Chinese Journal of Chemistry 2017 Volume 35(Issue 6) pp:991-1000

Publication Date(Web):2017/06/01

DOI:10.1002/cjoc.201600853

AbstractDetails of a biogenetically inspired strategy that led to the synthesis of the hetidine-type C20-diterpenoid alkaloid skeleton are reported in this paper. Key steps of our synthesis include a C—H oxidation to convert the atisine-type core to the ajaconine skeleton, as well as an aza-Prins cyclization that establishes the hetidine alkaloid skeleton. An unexpected heptacyclic framework bearing a unique tricyclo[3.3.1.02,7]nonane moiety has been obtained during our studies, which may represent a new type of C20-diterpenoid alkaloids yet to be discovered.

A Radical Cascade Enabling Collective Syntheses of Natural Products

Co-reporter:Xiaobei Wang, Dongliang Xia, Wenfang Qin, Ruijie Zhou, ... Yong Qin

Chem 2017 Volume 2, Issue 6(Volume 2, Issue 6) pp:

Publication Date(Web):8 June 2017

DOI:10.1016/j.chempr.2017.04.007

•Direct generation of nitrogen-centered radical from sulfonamide by photocatalysis•Radical cascade reactions with excellent selectivities•Efficient syntheses of 33 indole alkaloids and related analogs•Potential applications for the syntheses of other nitrogen-containing moleculesToday, achieving the chemical synthesis of a single natural product is rarely out of reach with sufficient manpower. However, considering the urgent demand for chemical biology studies and drug discovery, efficient preparation of a large collection of complex natural products and natural-product-like libraries with stereochemical and architectural divergence remains highly desirable. Here, we describe a visible-light-mediated radical cascade reaction that generates a nitrogen-centered radical from aniline-type sulfonamide and reverses the conventional reactivity between two electron-donating amine and enamine groups, allowing efficient syntheses of 33 complex indole alkaloids with varied architectures and divergent stereochemistry. This approach could be expanded to intermolecular reaction patterns and could be expected to facilitate the preparation of nitrogen-containing architectures, which are of great interest for the syntheses of natural products and bioactive substances.Natural products have long been important inspirations for the development of chemical methodologies, theories, and technologies, and ultimately, discoveries of new drugs and materials. Chemical syntheses have traditionally yielded individual or small groups of natural products; however, methodology development allowing the synthesis of a large collection of natural products remains scarce. Here, we report an efficient photocatalytic radical cascade method that enables access to libraries of chiral and multiple-ring-fused tetrahydrocarbolinones. The radical cascade can controllably introduce complexity and functionality into products with excellent chemo-, regio-, and diastereoselectivity. The power of this distinct method has been demonstrated by the efficient syntheses of 33 monoterpenoid indole alkaloids belonging to four families.Download high-res image (204KB)Download full-size image

Enabling syntheses of diterpenoid alkaloids and related diterpenes by an oxidative dearomatization/Diels–Alder cycloaddition strategy

Co-reporter:Xiao-Yu Liu

Natural Product Reports (1984-Present) 2017 vol. 34(Issue 9) pp:1044-1050

Publication Date(Web):2017/08/30

DOI:10.1039/C7NP00033B

Covering: 2015 to March 2017 ortho-Benzoquinones generated from dearomatization of aromatic compounds are highly reactive intermediates in organic synthesis. One of their most important applications involves the participation in Diels–Alder cycloadditions, facilitating rapid access to molecular complexity. This powerful strategy has recently been utilized in the syntheses of diverse diterpenoid alkaloids and their biogenetically relevant diterpenes, which is the subject of this Highlight.

Formal total synthesis of the akuammiline alkaloid (+)-strictamine

Co-reporter:Tao Xiao;Zhi-Tao Chen;Lin-Feng Deng;Dan Zhang;Xiao-Yu Liu;Hao Song

Chemical Communications 2017 vol. 53(Issue 94) pp:12665-12667

Publication Date(Web):2017/11/23

DOI:10.1039/C7CC08153G

An asymmetric formal total synthesis of the akuammiline alkaloid (+)-strictamine is reported. The key features of the synthesis include a Friedel–Crafts cyclization to form the D-ring and the critical C7 all-carbon quaternary carbon centre, as well as an aza-1,6-conjugate addition to assemble the 2-azabicyclo[3.3.1]nonane system.

Formal Synthesis of Anticoagulant Drug Fondaparinux Sodium

Co-reporter:Xiang Dai, Wentao Liu, Qilong Zhou, Chunwei Cheng, Chao Yang, Shuqing Wang, Min Zhang, Pei Tang, Hao Song, Dan Zhang, and Yong Qin

The Journal of Organic Chemistry 2016 Volume 81(Issue 1) pp:162-184

Publication Date(Web):December 9, 2015

DOI:10.1021/acs.joc.5b02468

The practical formal synthesis of the anticoagulant drug fondaparinux sodium 1 was accomplished using an optimized modular synthetic strategy. The important pentasaccharide 2, a precursor for the synthesis of fondaparinux sodium, was synthesized on a 10 g scale in 14 collective steps with 3.5% overall yield from well-functionalized monosaccharide building blocks. The strategy involved a convergent [3 + 2] coupling approach, with excellent stereoselectivity in every step of glycosylation from the monosaccharide building blocks. Efficient routes to the syntheses of these fully functionalized building blocks were developed, minimizing oligosaccharide stage functional-group modifications. The syntheses of all building blocks avoided rigorous reaction conditions and the use of expensive reagents. In addition, common intermediates and a series of one-pot reactions were employed to enhance synthetic efficiency, improving the yield considerably. In the monosaccharide-to-oligosaccharide assembly reactions, cheaper activators (e.g., NIS/TfOH, TESOTf, and TfOH) were used to facilitate highly efficient glycosylations. Furthermore, crystallization of several monosaccharide and oligosaccharide intermediates significantly simplified purification procedures, which would be greatly beneficial to the scalable synthesis of fondaparinux sodium.

Synthetic approach to the functionalized tricyclic core of atropurpuran

Co-reporter:Huan Chen, Xiao-Huan Li, Jing Gong, Hao Song, Xiao-Yu Liu, Yong Qin

Tetrahedron 2016 Volume 72(Issue 2) pp:347-353

Publication Date(Web):14 January 2016

DOI:10.1016/j.tet.2015.11.050

A strategy for synthesizing the tricyclic fragment 5 of atropurpuran 1 is reported. Rings A and C of atropurpuran were assembled stereoselectively via two intramolecular Michael additions. The advanced tricyclic skeleton 5 shows the correct functionality and stereochemistry for atropurpuran 1, so the skeleton may serve as a key intermediate in its total synthesis.

Asymmetric Michael Addition Induced by (R)-tert-Butanesulfinamide and Syntheses of Chiral Pyrazolidinone Derivatives

Co-reporter:Hong-Xiu Huang, Hui-Jing Wang, Ling Tan, Shu-Qing Wang, Pei Tang, Hao Song, Xiao-Yu Liu, Dan Zhang, and Yong Qin

The Journal of Organic Chemistry 2016 Volume 81(Issue 21) pp:10506-10516

Publication Date(Web):July 20, 2016

DOI:10.1021/acs.joc.6b01237

A highly diastereoselective Michael addition of (R)-N-tert-butanesulfinyl imidates 8 to α,β-unsaturated pyrazolidinone 3a has been developed to afford pyrazolidinones 10 possessing three contiguous stereocenters with good to excellent yield and excellent diastereoselectivity. A two-step conversion of reduction and cyclization provides the bicyclic pyrazolopiperidine 12 in a good yield. A series of pyrazolopiperidine derivatives 18 with a quaternary carbon center at C-3a are stereoselectively synthesized via alkylation or Michael addition.

Total synthesis of (−)-depyranoversicolamide B

Co-reporter:Wen-Fang Qin, T. Xiao, D. Zhang, Lin-Feng Deng, Y. Wang and Y. Qin

Chemical Communications 2015 vol. 51(Issue 89) pp:16143-16146

Publication Date(Web):10 Sep 2015

DOI:10.1039/C5CC05877E

Starting from easily prepared (R)-C3-isoprenylated pyrroloindoline, the C3-isoprenylated indolyl diketopiperazine is prepared by an efficient reductive opening of the pyrrolo ring, and undergoes biomimetic Diels–Alder reaction to generate an anti-adduct as a sole stereoisomer. Oxidation of the indoline moiety to oxindole completes the synthesis of (−)-depyranoversicolamide B.

Ongoing Pursuit of Diterpenoid Alkaloids: A Synthetic View

Co-reporter:Dr. Xiao-Yu Liu ; Yong Qin

Asian Journal of Organic Chemistry 2015 Volume 4( Issue 10) pp:1010-1019

Publication Date(Web):

DOI:10.1002/ajoc.201500295

Abstract

The incorporation of nitrogen atoms into policyclic diterpenes has led to one of the most fascinating group of natural products with cage-like structures: diterpenoid alkaloids. Their singular architectural features and significant bioactivities made them highly pursued targets amongst the synthetic community over decades. A total of seven types of diterpenoid alkaloid molecules have been synthesized thus far, and the research in this area experienced a new climax in the past five years. With a brief overview and summary of the historic achievements, this Focus Review particularly covers the recent, post-2010 advances in the field of diterpenoid alkaloid synthesis, highlighting the utilization of innovative synthetic methods and strategies. Despite numerous achievements, there are still a number of such alkaloids with different and unique structural types waiting to be accomplished, implying that the pursuit is far from ending.

Total Syntheses of ()-Isoschizogamine and ()-2-Hydroxyisoschizogamine

Co-reporter:Xiaobei Wang;Dongliang Xia;Ling Tan;Huan Chen;Hongxiu Huang;Dr. Hao Song ;Dr. Yong Qin

Chemistry - A European Journal 2015 Volume 21( Issue 41) pp:14602-14607

Publication Date(Web):

DOI:10.1002/chem.201502869

Abstract

Total syntheses of (−)-isoschizogamine and (−)-2-hydroxyisoschizogamine are described. The synthesis employs two asymmetric Michael additions to establish chiral centers at C7 and the quaternary carbon C20. Regioselective reduction of the methylthioiminium cation rather than the enamine generates an isoschizogamine-type pentacyclic skeleton. Acidic hydrolysis of the isoschizogamine-type intermediate in the absence of oxygen provides natural (−)-isoschizogamine. Conducting the reaction in the presence of oxygen leads to a multistep oxidative hydrolysis cascade that affords unnatural (−)-2-hydroxyisoschizogamine.

Total Synthesis of ()-LundurineA and Determination of its Absolute Configuration

Co-reporter:Shuaijiang Jin;Jing Gong ; Yong Qin

Angewandte Chemie 2015 Volume 127( Issue 7) pp:2256-2259

Publication Date(Web):

DOI:10.1002/ange.201409963

Abstract

A 15-step total synthesis of (−)-lundurine A (1) from easily accessible (S)-pyrrolidinone 18 is reported. A Simmons-Smith reaction allows the efficient, simultaneous assembly of the cyclopropyl C ring, the six-membered D ring, the seven-membered E ring, and the quaternary carbon stereocenters at C2 and C7. The absolute configuration of natural (−)-lundurine A was deduced to be 2R,7R,20R based on the stepwise construction of the stereocenters during the total synthesis.

Total Synthesis of Lignan Lactone (–)-Hinokinin

Co-reporter:Qi-Long Zhou;Hui-Jing Wang;Pei Tang;Hao Song

Natural Products and Bioprospecting 2015 Volume 5( Issue 5) pp:255-261

Publication Date(Web):2015 October

DOI:10.1007/s13659-015-0073-3

This research paper is aimed at studying the total synthesis of pharmacologically active lignan (–)-hinokinin. The synthesis features a three-step cascade reaction involving highly stereoselective Michael addition, anion-oxidative hydroxylation, and oxygen anion cyclization to construct the pivotal butyrolactonimidate intermediate.

One-Pot Synthesis of Multisubstituted Butyrolactonimidates: Total Synthesis of (−)-Nephrosteranic Acid

Co-reporter:Huijing Wang, Pei Tang, Qilong Zhou, Dan Zhang, Zhitao Chen, Hongxiu Huang, and Yong Qin

The Journal of Organic Chemistry 2015 Volume 80(Issue 5) pp:2494-2502

Publication Date(Web):February 11, 2015

DOI:10.1021/jo5029166

Multisubstituted chiral butyrolactonimidates have been synthesized via a one-pot, three-step cascade reaction in which (R)-N-tert-butanesulfinyl imidates and α,β-unsaturated diesters undergo highly stereoselective Michael addition, anion-oxidative hydroxylation, and cyclization. The synthesized butyrolactonimidates are versatile intermediates for preparation of substituted butyrolactones and furans. The usefulness of this cascade reaction is demonstrated through the concise total synthesis of natural product (−)-nephrosteranic acid.

Total Synthesis of ()-LundurineA and Determination of its Absolute Configuration

Co-reporter:Shuaijiang Jin;Jing Gong ; Yong Qin

Angewandte Chemie International Edition 2015 Volume 54( Issue 7) pp:2228-2231

Publication Date(Web):

DOI:10.1002/anie.201409963

Abstract

Total Syntheses of Ainsliadimer B and Gochnatiolides A and B

Co-reporter:Dongliang Xia;Yu Du;Zhi Yi;Hao Song;Dr. Yong Qin

Chemistry - A European Journal 2013 Volume 19( Issue 14) pp:4423-4427

Publication Date(Web):

DOI:10.1002/chem.201204292

Silver-promoted Friedel–Crafts reaction: concise total synthesis of (−)-ardeemin, (−)-acetylardeemin and (−)-formylardeemin

Co-reporter:Y. Wang, C. Kong, Y. Du, H. Song, D. Zhang and Y. Qin

Organic & Biomolecular Chemistry 2012 vol. 10(Issue 14) pp:2793-2797

Publication Date(Web):02 Mar 2012

DOI:10.1039/C2OB00014H

Total syntheses of multidrug resistant inhibitors (−)-acetylardeemin 2a, (−)-ardeemin 2b, and (−)-formylardeemin 3 have been achieved within 10 steps starting from bromopyrroloinoline 13. The key step involves direct alkylation of 13 with prenyl tributylstannane 11 to yield 12via a silver-promoted asymmetric Friedel–Crafts reaction. Highly efficient installation of the isoprenyl group allowed excellent overall yield. Moreover, the substrate scope of the asymmetric Friedel–Crafts reaction of 13 was expanded to include a variety of arenes 14 to afford natural product-like library analogues 15.

Biomimetic Total Synthesis of (+)-Gelsemine

Co-reporter:Xuan Zhou;Tao Xiao;Yusuke Iwama;Dr. Yong Qin

Angewandte Chemie International Edition 2012 Volume 51( Issue 20) pp:4909-4912

Publication Date(Web):

DOI:10.1002/anie.201201736

Biomimetic Total Synthesis of (+)-Gelsemine

Co-reporter:Xuan Zhou;Tao Xiao;Yusuke Iwama;Dr. Yong Qin

Angewandte Chemie 2012 Volume 124( Issue 20) pp:4993-4996

Publication Date(Web):

DOI:10.1002/ange.201201736

Total Synthesis of Indoline Alkaloids: A Cyclopropanation Strategy

Co-reporter:Dan Zhang, Hao Song, and Yong Qin

Accounts of Chemical Research 2011 Volume 44(Issue 6) pp:447

Publication Date(Web):April 14, 2011

DOI:10.1021/ar200004w

Indoline alkaloids constitute a large class of natural products; their diverse and complex structures contribute to potent biological activities in a range of molecules. Designing an appropriate strategy for the total synthesis of indoline alkaloids is a difficult task that depends on being able to efficiently assemble the core architectures. The best strategies allow access to a variety of different indoline alkaloid structures in a minimum of steps. The cyclopropanation of simple olefins and the subsequent synthetic transformation of the resulting cyclopropyl intermediates has been intensively studied in recent decades. In contrast, the cyclopropanation of enamines, especially for the construction of complex nitrogen-containing ring systems, remained relatively unexplored. Previous success with the cyclopropanation of simple indoles to form stable indolylcyclopropanocarboxylates encouraged us to explore the assembly of indoline alkaloid skeletons with cyclopropanation as a key reaction. Theoretically, indolylcyclopropanocarboxylates are doubly activated by a vicinally substituted amino group and carboxyl group; that is, they are typical donor−acceptor cyclopropanes. Accordingly, they tend to yield an active iminium intermediate, which can undergo inter- and intramolecular nucleophilic reactions to form the core structure of indoline alkaloids with an expanded ring system. In this Account, we summarize our efforts to develop a cascade or stepwise reaction of cyclopropanation/ring-opening/iminium cyclization (the CRI reaction) on tryptamine derivatives for assembling indoline alkaloid skeletons.With the CRI approach, three types of indoline alkaloid skeletons have been efficiently constructed: (i) hexahydropyrrolo[2,3-b]indoline (type I), (ii) tetrahydro-9a,4a-iminoethano-9H-carbazole (type II), and (iii) tetrahydroquinolino[2,3-b]indoline (type III). The effects of substituents on tryptamine derivatives were carefully investigated for inter- and intramolecular CRI reactions during construction of type I and type II skeletons. These results provided a basis for the further design and synthesis of complex natural products containing nitrogen.The usefulness of the CRI reaction is well demonstrated by our total synthesis of structurally intriguing indoline alkaloids such as N-acetylardeemin, minfiensine, vincorine, and communesin F. In addition, we highlight advances by other groups in construction of the three types of skeletons as well as their total syntheses of these indoline alkaloids. Discussion of the total syntheses of these indoline alkaloids focuses on comparing the individual synthetic strategies for forming the ring systems embedded in the final products.We also describe the total synthesis of perophoramidine, which has the same type III skeleton as communesin F. The observation of a retro Diels−Alder reaction during our synthesis of communesin F inspired the hetero Diels−Alder reaction on which our total synthesis of perophoramidine was based.

Synthesis of 3-substituted 8,9-didehydroazepino[4,5-b]indolines via ring expansion reaction of pyrroloindolines

Co-reporter:Fu-Sheng Wang, Dan Zhang, Chen Kong, Yong Qin

Tetrahedron Letters 2011 Volume 52(Issue 26) pp:3295-3297

Publication Date(Web):29 June 2011

DOI:10.1016/j.tetlet.2011.04.061

An unexpected ring expansion reaction was observed to give the 3-substituted 8,9-didehydroazepinoindolines when 3-substituted pyrroloindolines reacted with electron-deficient acetylenes in the presence of catalytic amount of CuI. The ring expansion reaction proceeded via a three-step one-pot cascade pathway of aza-Michael-addition/ring-opening/iminium-cyclization.

An Efficient Synthesis of a ()-Physostigmine's Library for Identifying Potential Anti-Alzheimer's Agents

Co-reporter:Yi Wu;Fusheng Wang;Hao Song

Helvetica Chimica Acta 2011 Volume 94( Issue 8) pp:1496-1505

Publication Date(Web):

DOI:10.1002/hlca.201100020

Abstract

An efficient route for the synthesis of (−)-physostigmine analogs 1a–1g and 2a–2k is described. Analogs 1a–1g were synthesized via copper(I)-catalyzed cycloaddition between the optically pure azide 10 and a variety of alkynes. Similarly, analogs 2a–2k were prepared through ‘three-component Huisgen cycloaddition’ using various amines, propargyl bromine, and 10 in H₂O. Facile preparation of 10via MacMillan's organocatalysis has made it possible to generate a great diversity of natural product-like compounds that can be screened for anti-Alzheimer's effects.

Total Synthesis of (+)-Perophoramidine and Determination of the Absolute Configuration

Co-reporter:Haoxing Wu ; Fei Xue ; Xue Xiao

Journal of the American Chemical Society 2010 Volume 132(Issue 40) pp:14052-14054

Publication Date(Web):September 21, 2010

DOI:10.1021/ja1070043

The first asymmetric total synthesis of (+)-perophoramidine has been achieved in 17 steps with ∼11% overall yield. The key step relies on an asymmetric biomimetic Diels−Alder reaction between the in situ-generated chiral diene T-24 and the substituted tryptamine 23 to assemble the core structure 27a in a highly efficient way. An acid-catalyzed thermodynamic equilibrium results in C═N double-bond migration of the amidine moiety in 37, which guarantees a regioselective methylation on N1 at the end of the synthesis. The absolute configuration of (+)-perophoramidine was determined by X-ray crystallographic analysis of the chiral intermediate 32 and comparison of the rotation of synthetic (+)-perophoramidine with that of the natural product.

Synthesis and biological evaluation of novel 3′-N-tert-butylsulfonyl analogues of docetaxel

Co-reporter:Bowen Ke, Yong Qin, Fengyan Zhao, Yi Qu

Bioorganic & Medicinal Chemistry Letters 2008 Volume 18(Issue 17) pp:4783-4785

Publication Date(Web):1 September 2008

DOI:10.1016/j.bmcl.2008.07.101

Novel 3′-N-tert-butylsulfonyl analogues 10a–c of docetaxel were synthesized and their biological evaluation in cytotoxicity in vitro against several human tumor cell lines were presented. The biologically tested results showed that N-oxide pyridyl substituted10b–c had potent cytotoxicities against human tumor cell lines Eca-109, SKOV3, SMMC-7721, HCT-8, PC3, MCF-7, HeLa and KB.The synthesis of three novel 3′-N-tert-butylsulfonyl analogues of docetaxel 10a–c with potent cytotoxicity against several human tumor cell lines is reported.

Efficient Assembly of an Indole Alkaloid Skeleton by Cyclopropanation: Concise Total Synthesis of ()-Minfiensine

Co-reporter:Liqun Shen;Min Zhang;Yi Wu Dr.

Angewandte Chemie 2008 Volume 120( Issue 19) pp:3674-3677

Publication Date(Web):

DOI:10.1002/ange.200800566

Efficient Assembly of an Indole Alkaloid Skeleton by Cyclopropanation: Concise Total Synthesis of ()-Minfiensine

Co-reporter:Liqun Shen;Min Zhang;Yi Wu Dr.

Angewandte Chemie International Edition 2008 Volume 47( Issue 19) pp:3618-3621

Publication Date(Web):

DOI:10.1002/anie.200800566

Silver-promoted Friedel–Crafts reaction: concise total synthesis of (−)-ardeemin, (−)-acetylardeemin and (−)-formylardeemin

Co-reporter:Y. Wang, C. Kong, Y. Du, H. Song, D. Zhang and Y. Qin