Ang Li, Ph.D.

Professor

State Key Laboratory of Bioorganic and Natural Product Chemistry

Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences

345 Lingling Road

Shanghai 200032, China

Tel: 86–21–54925466

E-mail: ali@sioc.ac.cn

Research group website: http://angligroup.sioc.ac.cn/

Research Area

Organic synthesis: total synthesis of structurally and biologically interesting natural products

Teaching

Reactions in organic synthesis

Professional Experience

2010–present Professor, State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute

of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.

2010 Research fellow, Institute of Chemical and Engineering Sciences, Singapore.

Advisor: Prof. K. C. Nicolaou.

Education

2004–2009 Ph.D., The Scripps Research Institute, California, USA

Advisor: Prof. K. C. Nicolaou

2000–2004 B.Sc., Peking University, Beijing, China

Advisor: Prof. Zhen Yang

Honors and Awards

2016 ChemComm Emerging Investigator Lectureship

2015 The National Science Fund for Distinguished Young Scholars (国家杰出青年基金)

2015 WuXi PharmaTech Life Science and Chemistry Award

2015 Roche Chinese Young Investigators Award

2013 Asian Core Program Lectureship Award

2013 Chinese Chemical Society Wei-Shan Award for Synthetic Chemistry

2013 China Pharmaceutical Association–Servier Youth Medicinal Chemist Award

2013 Thieme Chemistry Journal Award

2012 Asian Core Program Lectureship Award

2009 Eli Lilly Graduate Fellowship

2007 Chinese Government Award for Outstanding Graduate Students Abroad

2007 Bristol-Myers Squibb Graduate Fellowship in Organic Synthesis

Research Grants

2016–2020 国家杰出青年基金, ¥ 4,000,000.

2013–2015 国家自然科学基金委优秀青年基金, ¥ 1,000,000.

2013–2016 中组部青年拔尖人才支持计划, ¥ 2,400,000.

2013–2015 中科院科技创新交叉与合作团队, ¥ 1,000,000.

2013–2017 科技部973计划青年专题, "The synthesis, target identification, and mode of action of several natural

products that regulate biological events", ¥ 5,000,000.

Publications

1. P. Yang, M. Yao, J. Li, Y. Li, A. Li,* Total synthesis of rubriflordilactone B, Angew. Chem. Int. Ed. DOI:

10.1002/anie.201601915.

2. Y. Li, S. Zhu, J. Li, A. Li,* Asymmetric total syntheses of aspidodasycarpine, lonicerine, and the proposed

structure of lanciferine, J. Am. Chem. Soc. DOI: 10.1021/jacs.6b00764.

3. X. Yang, D. Wu, Z. Lu, H. Sun,* A. Li,* A mild preparation of alkynes from alkenyl triflates, Org. Biomol.

Chem. DOI: 10.1039/C6OB00345A.

4. Y. Sun, Z. Meng, P. Chen, D. Zhang, M. Baunach, C. Hertweck, A. Li,* A concise total synthesis of sespenine, a

structurally unusual indole terpenoid from Streptomyces, Org. Chem. Front. 2016, 3, 368–374.

5. M. Yang, X. Yang, H. Sun, A. Li,* Total Synthesis of Ileabethoxazole, Pseudopteroxazole, and

seco-Pseudopteroxazole, Angew. Chem. Int. Ed. 2016, 55, 2851.

6. Z. Lu, H. Li, M. Bian, A. Li,* Total Synthesis of Epoxyeujindole A, J. Am. Chem. Soc. 2015, 137, 13764–13767.

7. S. Zhou, H. Chen, Y. Luo, W. Zhang, A. Li,* Asymmetric total synthesis of mycoleptodiscin A, Angew. Chem.

Int. Ed. 2015, 54, 6878–6882.

8. X. Xiong, D. Zhang, J. Li, Y. Sun, S. Zhou, M. Yang, H. Shao,* A. Li,* Synthesis of indole terpenoid mimics via

a functionality-tolerated Eu(fod)3-catalyzed conjugate addition, Chem. Asian J. 2015, 10, 869–872.

9. M. Wan, M. Yao, J. Gong, P. Yang, H. Liu,* A. Li,* Synthesis of the tetracyclic core of chlorospermines, Chin.

Chem. Lett. 2015, 26, 272–276.

10. M. Yang, J. Li, A. Li,* Total synthesis of clostrubin, Nature Communications 2015, 6, 6445.

11. Z. Meng, H. Yu, L. Li, W. Tao, H. Chen, M. Wan, D. J. Edmonds, J. Zhong, A. Li,* Total synthesis and antiviral

activity of indolosesquiterpenoids from the xiamycin and oridamycin families, Nature Communications 2015, 6,

6096.

12. H. Li, Y. Sun, Q. Zhang, Y. Zhu, S.-M. Li, A. Li, C. Zhang,* Elucidating the cyclization cascades in xiamycin

biosynthesis by substrate synthesis and enzyme characterizations, Org. Lett. 2015, 17, 306–309.

13. J. Li, P. Yang, M. Yao, J. Deng, A. Li,* Total synthesis of rubriflordilactone A, J. Am. Chem. Soc. 2014, 136,

16477–16480.

14. Z. Lu, M. Yang, P. Chen, X. Xiong, A. Li,* Total synthesis of hapalindole-type natural products, Angew. Chem.

Int. Ed. 2014, 53, 13840–13844.

15. S. Zhou, D. Zhang, Y. Sun, R. Li, W. Zhang, A. Li,* Intermolecular conjugate addition of pyrroloindoline and

furoindoline radicals to α,β-unsaturated enones via photoredox catalysis, Adv. Synth. Catal. 2014, 356,

2867–2872.

16. Y. Sun, P. Chen, D. Zhang, M. Baunach, C. Hertweck, A. Li,* Bioinspired total synthesis of sespenine, Angew.

Chem. Int. Ed. 2014, 53, 9012–9016.

17. J. Deng, S. Zhou, W. Zhang, J. Li, R. Li, A. Li,* Total synthesis of taiwaniadducts B, C, and D, J. Am. Chem. Soc.

2014, 136, 8185–8188.

18. C. Wan, J. Deng, H. Liu,* M. Bian,* A. Li,* Recent advances of intermolecular Diels–Alder reaction in

bio-inspired synthesis of natural products, Sci. China Chem. 2014, 57, 926–929.

19. X. Xiong, Y. Li, Z. Lu, M. Wan, S. Wu, H. Shao,* A. Li*, Synthesis of the 6,6,5,7-tetracyclic core of

daphnilongeranin B, Chem. Commun. 2014, 50, 5294–5297.

20. H. Yu, C. Wan, J. Han,* A. Li,* A protocol for α-bromination of β-substituted enones, Acta Chim. Sinica 2013,

71, 1488.

21. Y. Sun, R. Li, W. Zhang, A. Li,* Total synthesis of indotertine A and drimentines A, F, and G, Angew. Chem. Int.

Ed. 2013, 52, 9201–9204.

22. Z. Lu, Y. Li, J. Deng, A. Li,* Total synthesis of the Daphniphyllum alkaloid daphenylline, Nature Chemistry,

2013, 5, 679–684.

23. J. Deng, R. Li, Y. Luo, J. Li, S. Zhou, Y. Li, J. Hu, A. Li,* Divergent total synthesis of taiwaniaquinones A and F

and taiwaniaquinols B and D, Org. Lett. 2013, 15, 2022–2025.

24. S. Li, J. Han,* A. Li,* Interrupted fisher indole synthesis and its applications to alkaloid synthesis, Acta Chim.

Sinica 2013, 73, 295–298.

25. M. Bian, Z. Wang, X. Xiong, Y. Sun, C. Matera, K. C. Nicolaou,* A. Li,* Total syntheses of anominine and

tubingensin A, J. Am. Chem. Soc. 2012, 134, 8078–8081.

26. J. Deng, B. Zhu, Z. Lu, H. Yu, A. Li,* Total synthesis of (–)-fusarisetin A and reassignment of the absolute

configuration of its natural counterpart, J. Am. Chem. Soc. 2012, 134, 920–923.

27. C.-C. Tseng, H. Ding, A. Li, Y. Guan, D. Y.-K. Chen, A modular synthesis of salvileucalin B structural domains,

Org. Lett. 2011, 13, 4410–4413.

28. K. C. Nicolaou, A. Li, D. J. Edmonds, G. S. Tria, S. P. Ellery, Total syntheses of platensimycin and related

natural products, J. Am. Chem. Soc. 2009, 131, 16905–16918.

29. K. C. Nicolaou, A. Li, S. P. Ellery, D. J. Edmonds, Rhodium-catalyzed asymmetric enyne cycloisomerization of

terminal alkynes and formal total synthesis of (–)-platensimycin, Angew. Chem. Int. Ed. 2009, 48, 6293–6295.

30. K. C. Nicolaou, A. F. Stepan, T. Lister, A. Li, A. Montero, G. S. Tria, C. I. Turner, Y. Tang, J. Wang, R. M.

Denton, D. J. Edmonds, Design, synthesis and biological Evaluation of platensimycin analogs with varying

degrees of molecular complexity, J. Am. Chem. Soc. 2008, 13110–13119.

31. K. C. Nicolaou, A. Li, Total syntheses and structural revision of α- and β-diversonolic esters and total syntheses

of diversonol and blennolide C, Angew. Chem. Int. Ed. 2008, 47, 6579–6582.

32. K. C. Nicolaou, Y. Tang, J. Wang, A. F. Stepan, A. Li, A. Montero, Total synthesis and antibacterial properties

of carbaplatensimycin, J. Am. Chem. Soc. 2007, 129, 14850–14851.

33. K. C. Nicolaou, D. J. Edmonds, A. Li, G. S. Tria, Asymmetric total syntheses of platensimycin, Angew. Chem.

Int. Ed. 2007, 46, 3942–3945.

34. K. C. Nicolaou, A. Li. D. J. Edmonds, Total synthesis of platensimycin, Angew. Chem. Int. Ed. 2006, 45,

7086–7090.

35. K. C. Nicolaou, R. M. Denton, A. Lenzen, D. J. Edmonds, A. Li, R. M. Milburn, S. T. Harrison, Stereocontrolled

synthesis of model core systems of lomaiviticins A and B, Angew. Chem. Int. Ed. 2006, 45, 2076–2081.

36. B. Liang, J. Liu, Y.-X. Gao, K. Wongkhan, D.-X. Shu, Y. Lan, A. Li, A. S. Batsanov, J. A. H. Howard, T. B.

Marder, J.-H. Chen, Z. Yang, Synthesis of thiourea-oxazolines, a new class of chiral S,N-heterobidentate ligands:

application in Pd-catalyzed asymmetric bis(methoxycarbonylation) of terminal olefins, Organometallics 2007, 26,

4756–4762.

37. Z. Xiong, N. Wang, M. Dai, A. Li, J. Chen, Z. Yang, Synthesis of novel palladacycles and their application in

Heck and Suzuki reactions under aerobic conditions, Org. Lett. 2004, 6, 3337–3340.

38. Y. Zhang, A. Li, Z. Yan, G. Xu, C. Liao, C. Yan, (ZrO2)0.85(REO1.5)0.15 (RE = Sc, Y) solid solutions prepared via

three Pechini-type gel routes: 1. gel formation and calcination behaviors, Journal of Solid State Chemistry 2003,

171, 434–438.

39. Y. Zhang, A. Li, Z. Yan, G. Xu, C. Liao, C. Yan, (ZrO2)0.85(REO1.5)0.15 (RE=Sc, Y) solid solutions prepared via

three Pechini-type gel routes: 2-sintering and electrical properties, Journal of Solid State Chemistry 2003, 171,

439–443.

40. Y. Zhang, A. Li, Z. Yan, C. Liao, C. Yan, Calcination time effects on the particle size, specific surface area and

morphology of rare earth oxides (III), Journal of the Chinese Rare Earth Society (Chinese Edition) 2002, 20,

170–172.

41. Y. Zhang, Z. Yan, A. Li, X, Jiang, L. Gu, C. Liao, C. Yan, Effects of precipitation conditions on specific surface

area and morphology of rare earth oxides (II), Journal of the Chinese Rare Earth Society (Chinese Edition) 2001,

19, 471–473.

Funding

2016–2020 The National Science Fund for Distinguished Young Scholars, 4,000,000 RMB.

2013–2017 973 Program for Young Scientists, 4,920,000 RMB.

2013–2015 Chinese Academy of Sciences Multidisciplinary Research Team, 1,000,000 RMB.

2013–2016 中组部Young Scientist Plan, 2,400,000 RMB.

2013–2015 National Natural Science Foundation Fund for Excellent Young Scholars, 1,000, 000 RMB.

Academic Activities

2016– Editorial board, Chin. Chem. Lett.

Invited Lectures

1 Divergent Total Synthesis of Natural Products, The 1st Natural Product Synthesis Symposium for Young

Chemists, Shanghai, China, 06/19/2012.

2. Divergent Total Synthesis of Indole Terpenoids, The 8th Sino-US Chemistry Professor Conference, Kunming,

China, 07/02/2012.

3. Total Synthesis of Fusarisetin A, The 4th Young Investigators Workshop of the Organic Division of EuCheMs,

Vienna, Austria, 08/25/2012.

4. Total Synthesis of Daphenylline via 6π Electrocyclization, The 1st International Symposium on the Natural

Product Synthesis and Process Methods for Drug Manufacture, Chongqing, China, 09/27/2012.

5. Total Synthesis of Daphenylline, New Horizons in Natural Product Synthesis Symposium, Nottingham, UK,

11/22/2012.

6. 6π Electrocyclization in Natural Product Synthesis, The 7th International Conference on Cutting-Edge Organic

Chemistry in Asia, Singapore, 12/12/2012.

7. To Travel and to Arrive: A Fascinating Journey of Natural Product Synthesis, The 2nd Natural Product Synthesis

Symposium for Young Chemists, Beijing, China, 06/18/2013.

8. Total Synthesis of the Daphniphyllum Alkaloid Daphenylline, The 8th National Conference on Chemical Biology

of China, Shanghai, China, 09/17/2013.

9. Synthesizing Natural Products with 6π Electrocyclization, 2013 Shanghai International Conference on

Traditional Chinese Medicine and Natural Medicine, Shanghai, China, 10/17/2013.

10. Bioinspired Aza-Prins Cyclization in Syntheses of Indole Natural Products, The 8th National Organic Chemistry

Conference, Chongqing, China, 10/19/2013.

11. 6π Electrocyclization for Synthesizing Natural Products, 2013 Roche and Royal Society of Chemistry

Symposium, Shanghai, China, 10/24/2013.

12. Total Synthesis of Polycyclic Natural Products Using 6π Electrocyclization, 2013 National Medicinal

Symposium, Jinan, China, 11/01/2013.

13. Aza-Prins Cyclization in Natural Product Synthesis, The 3rd Junior International Conference on Cutting-Edge

Organic Chemistry in Asia, Chiba, Japan, 11/23/2013.

14. Total Synthesis of Taiwaniaquinoids, The 3rd Phase Asian Core Program Startup Symposium, Hsinchu,

04/20/2014.

15. Total Synthesis of Sespenine: A Bioinspired Aza-Prins Approach, The 10th Sino-US Chemistry Professor

Conference, Jinan, China, 06/16/2014.

16 The Detours in Bioinspired Natural Product Synthesis, The 3rd Natural Product Synthesis Symposium for Young

Chemists, Lanzhou, China, 08/17/2014.

17 The 6π Electrocyclization in Natural Product Synthesis, The 2nd International Symposium on Natural Product

Synthesis and Innovative Process Methods for Drug Manufacture, Nanjing, 09/23/2014.

18 The Prins-Type Cyclization in Indole Terpenoid Synthesis, The 9th Syngenta International Conference,

10/10/2014.

19 Total Synthesis of Indole Terpenoids, The 11th National Synthetic Organic Chemistry Symposium, Shanghai,

China, 10/19/2014.

20 Electrocyclization/Aromatization as a Powerful Strategy in Natural Product Synthesis, The 13th International

Symposium for Chinese Organic Chemists, Xiamen, China, 12/21/2014.

21 Total Synthesis of Indole Terpenoids, The 2nd Organic Chemistry Frontiers International Symposium, Hangzhou,

04/21/2015.

23 The Development of Electrocyclization/Aromatization Strategies in Natural Product Synthesis, The 8th

Sino-German Frontiers of Science Symposium, Potsdam, Germany, 05/29/2015.

25 Synthesis of Natural Products with Multisubstituted Arenes, The 2nd Element Organic Chemistry Symposium,

Tianjin, China, 07/11/2015

26 The Detours in Bioinspired Synthesis of Natural Products, The 9th National Organic Chemistry Conference,

Changchun, China, 07/30/2015.

27 Constructing Multisubstituted Arenes of Natural Products, 2015 Pharmaron Symposium, Beijing, China,

09/12/2015.

28 Prins Cyclization in Natural Product Synthesis, NSFC-RSC International Symposium on Emerging Frontiers in

Organic Synthesis, Shanghai, China, 10/09/2015.

29 Total Synthesis of Indole Diterpenoids, The 12th National Synthetic Organic Chemistry Symposium, Guilin,

China, 10/19/2015.

30 Assembling Multisubstituted Arenes of Natural Products, The 3rd Roche and RSC Chemistry Symposium on

Leading Science for Drug Discovery, Shanghai, China, 10/24/2015.

31 Synthesizing Multisubstituted Arenes of Natural Products, The 15th Tateshina Conference on Organic Chemistry,

Chino, Japan, 11/06/2015.

32 Studies of Natural Product Synthesis, Chinese Chemical Society 2015 Young Chemist Symposium, Fuzhou,

China, 12/26/2015.

Research Statement: Total Synthesis of Natural Products

Ang Li′s research at Shanghai Institute of Organic Chemistry (SIOC) has been focused on the synthesis of

structurally and biologically interesting natural products. His group has accomplished total syntheses of > 50

natural products (> 10 classes, Figure 1). Below was summarized the strategic applications of 6π

electrocyclization/aromatization, Prins cyclization, and Diels−Alder cycloaddition by his group.

1. The 6π electrocyclization/aromatization strategy.

The synthesis of multisubstituted arenes remains a challenge in natural product synthesis. The

conventional substitution methods, such as cross coupling and Friedel−Crafts reactions, are limited by the

availability and electronic properties of substrates; the positional selectivity is another issue. The advantages of

electrocyclization includes: a) the strong driving force; b) flexible and convergent approaches to triene

precursors; c) no functionalization (e.g. halogenation or metallation) required for the new C−C bond formation;

d) the separation of stereochemistry and connectivity problems. Importantly, the torquoselectivity of

electrocyclization is inconsequential in the case of arene synthesis. Thus, we exploit 6π

electrocyclization/aromatization strategy in the following syntheses of natural products possessing

multisubstituted arenes (Figure 2).

Total synthesis of daphenylline (Nat. Chem. 2013, 5, 679). The Daphniphyllum alkaloids are a large class

of natural products isolated from a genus of evergreen plants widely used in Chinese herbal medicine. They

display a remarkable range of biological activities, including anticancer, antioxidant, and vasorelaxation

properties as well as elevation of nerve growth factor. Daphenylline is a structurally unique member among the

predominately aliphatic Daphniphyllum alkaloids, and contains a tetrasubstituted arene moiety mounted on a

sterically compact hexacyclic scaffold. The Li group accomplished the first total synthesis of daphenylline. A

gold-catalyzed 6-exo-dig cyclization reaction and a subsequent intramolecular Michael addition reaction were

exploited to construct the bridged 6,6,5-tricyclic motif of the natural product at an early stage, and the aromatic

moiety was forged through a photoinduced olefin isomerization/6π-electrocyclization cascade followed by an

oxidative aromatization process. In addition, the gold catalyzed cyclization was exploited in our total syntheses

of aspidodasycarpine, lonicerine, and the proposed structure of lanciferine (J. Am. Chem. Soc. DOI:

10.1021/jacs.6b00764) very recently.

Total synthesis of indolosesquiterpenoids from the xiamycin and oridamycin families (Nat. Commun.

2015, 6, 6096). Xiamycin A is a representative member of an indolosesquiterpenoid family from Streptomyces.

The Li group employed a one-pot 6π electrocyclization/aromatization reaction as the key step of its total

synthesis. Oridamycins A and B were constructed through a similar strategy. The C23 hydroxy of the latter was

introduced by sp3 C−H bond oxidation at a late stage. Evaluation of the antiviral activity of these compounds

revealed that xiamycin A is a potent agent against herpes simplex virus–1 in vitro.

Total synthesis of clostrubin (Nat. Commun. 2015, 6, 6445). Clostrubin is an anaerobic

bacterium-derived polyphenol which displays potent antibiotic activities against drug-resistant bacteria. The Li

group accomplished the first total synthesis of clostrubin in 9 steps (the longest linear sequence). A

desymmetrization strategy was devised based on its inherent structural feature. A photoinduced 6π

electrocyclization followed by spontaneous aromatization constructed the hexasubstituted ring at a late stage.

Total synthesis of tubingensin A (J. Am. Chem. Soc. 2012, 134, 8078). The fungus-derived indole

diterpenoid tubingensin A possesses a multisubstituted carbazole motif. The Li group used a CuOTf-promoted

6-electrocyclization/aromatization sequence to build its pentacyclic scaffold and achieved the first total

synthesis.

Total synthesis of rubriflordilactone A (J. Am. Chem. Soc. 2014, 136, 16477). The Li group achieved the

first and asymmetric total synthesis of rubriflordilactone A, a Schisandraceae triterpenoid, in a convergent

manner. Two fragments were cross-coupled to give a functionalized cis-triene. A

6π-electrocyclization/aromatization sequence assembled the pentasubstituted arene, and a formal vinylogous

Mukaiyama aldol reaction introduced the butenolide side chain.

Total Synthesis of Ileabethoxazole, Pseudopteroxazole, and seco-Pseudopteroxazole (Angew. Chem.

Int. Ed. 2016, 55, 2851). The total syntheses of ileabethoxazole, pseudopteroxazole, and

seco-pseudopteroxazole, three antituberculosis diterpenoids that had been isolated from Pseudopterogorgia

elisabethae, were accomplished in a collective fashion. A cascade alkyne carbopalladation/Stille reaction was

exploited to construct a triene precursor with suitable geometry. A fully substituted arene was then assembled

through a key 6π electrocyclization/aromatization sequence, and served as an advanced common intermediate.

Two radical cyclizations led to the formation of the five- and six-membered rings of ileabethoxazole and

pseudopteroxazole, respectively, with the desired stereochemistry, and a straightforward side-chain elongation

delivered seco-pseudopteroxazole.

Total Synthesis of Rubriflordilactone B (Angew. Chem. Int. Ed. DOI: 10.1002/anie.201601915). We

accomplished the first and asymmetric total synthesis of rubriflordilactone B, a heptacyclic Schisandraceae

bisnortriterpenoid possessing a tetrasubstituted arene moiety. The left-hand fragment was accessed through a

chiral pool-based route, which was linked to the right-hand fragment via a Sonogashira coupling. The cis

geometry of electrocyclization substrates were established by hydrogenation or hydrosilylation of the alkyne.

An electrocyclization-aromatization sequence built the multisubstituted arene at a final stage. The

hydrosilylation approach was of significant advantage in terms of reaction scale and reproducibility and

intermediate stability.

2. The Prins cyclization strategy.

Prins reaction is undoubtedly a powerful reaction due to its strong thermodynamic driving force. However,

its applications have long been restricted because of following reactions: a) the substrates of intermolecular

Prins reaction easily decompose under the strongly acidic conditions required for activating the electrophile; b)

lack of directing groups on non-functionalized olefin substrates results in multiple competitive reaction

pathways of carbocation intermediates, giving a mixture of alcohols, halides, and olefins as products. The Li

group has focused the attention to Prins cyclization for 6-membered ring formation. Understanding the

reactivity of carbocation intermediates benefits the control of their reaction modes and pathways and thus

provides useful tools for complex indole terpenoid syntheses (Figure 3).

Total synthesis of indotetine A and drimentines A, F, and G (Angew. Chem. Int. Ed. 2013, 52, 9201).

The Li group employed an intermolecular radical conjugate addition via visible-light photoredox catalysis to

accomplish the first total syntheses of drimentines A, F, and G. A bioinspired aza-Prins cyclization was

exploited to convert drimentine F to indotertine A.

Total synthesis of sespenine (Angew. Chem. Int. Ed. 2014, 53, 9012). The first total synthesis of sespenine,

a structurally unusual indole sesquiterpenoid, was accomplished. A bioinspired aza-Prins/Friedel–Crafts/retro

Friedel–Crafts cascade reaction assembled its bridged tetrahydroquinoline core. Further investigations on the

aza-Prins cyclization implied that the C3 configuration of the hydroxyindolenine intermediate was crucial to the

biosynthesis of sespenine and its congener xiamycin A.

Total synthesis of hapalindole-type natural products (Angew. Chem. Int. Ed. 2014, 53, 13840). A

unified and bioinspired oxidative cyclization strategy was used in the first total syntheses of naturally occurring

12-epi-hapalindole Q isonitrile, hapalonamide H, deschloro 12-epi-fischerindole I nitrile, and deschloro

12-epi-fischerindole W nitrile, as well as the structural revision of the latter. Hapalindoles H and Q were also

synthesized. The cyclization was indeed an intramolecular Prins reaction of conjugated iminium ion generated

in situ by benzylic oxidation.

Total synthesis of epoxyeujindole A (J. Am. Chem. Soc. 2015, 137, 13764). The total synthesis of

epoxyeujindole A was accomplished for the first time. The synthesis features a late-stage cationic cyclization

strategy, which took advantage of an electron-rich olefinic substrate. The heavily substituted A ring was

constructed through a Suzuki−Miyaura coupling and a cationic cyclization, and the bridged fused B ring was

formed through a Prins reaction. The synthesis showcased the power of Prins reaction at the late of complex

molecule synthesis.

3. The Diels−Alder cycloaddition strategy.

Although Diels−Alder cycloaddition was initially discovered in an intermolecular manner, intramolecular

Diels−Alder reaction has attracted more attentions in both areas of methodology development and complex

molecule synthesis. Intermolecular Diels−Alder reaction is often used for preparing cyclic building blocks,

rather than works as a key step of putting complex and functionalized fragments together at a very late stage.

The Li group has taken full advantage of the power of Diels−Alder cycloaddition from the both aspects, to

synthesize natural products with congested 6-membered ring systems (Figure 4).

Total synthesis of (–)-fusarisetin A and reassignment of the absolute configuration of its natural

counterpart (J. Am. Chem. Soc. 2012, 134, 920). The first total synthesis of (–)-fusarisetin A, the enantiomer of

naturally occurring acinar morphogenesis inhibitor (+)-fusarisetin A, was accomplished in 13 steps, leading to

the reassignment of the absolute configuration of the natural product. The synthesis featured a Lewis

acid-promoted intramolecular Diels−Alder reaction, a palladium-catalyzed OC allylic rearrangement, a

chemoselective Wacker oxidation, and a Dieckmann condensation/hemi-ketalization cascade. The

stereochemical outcome of the Diels−Alder reaction was well controlled by the equatorial methyl in the

transition state.

Total synthesis of taiwaniadducts B, C, and D (J. Am. Chem. Soc. 2014, 136, 8185). The first total

syntheses of taiwaniadducts B, C, and D were accomplished. Two diterpenoid segments were prepared with

high enantiopurity, both through Ir-catalyzed asymmetric polyene cyclization. A sterically demanding

intermolecular Diels−Alder reaction promoted by Er(fod)3 assembled the scaffold of taiwaniadducts B and C. A

carbonyl-ene cyclization forged the cage motif of taiwaniadduct D at a late stage, providing over 200 mg of this

compound. During these studies, the Li group exploited the Ir-catalyzed polyene cyclization in the first total

synthesis of mycoleptodiscin A (Angew. Chem. Int. Ed. 2015, 54, 6878). The tetracyclic core was built with an

excellent level of enantiopurity, and a Cu mediated C−N bond formation was responsible for the late stage

pyrrole construction.

Appendix

Figure 1. Natural products synthesized by the Li group.

Figure 2. Natural products synthesized with the 6π electrocyclization/aromatization strategy.

Figure 3. Natural products synthesized during the studies of the Prins cyclization strategy.

Figure 4. Natural products synthesized during the studies of the Diels−Alder cycloaddition strategy.