1. Recent work in the research of Daphniphyllum alkaloids with diverse complex structures and unique biosynthetic pathways continue to attract attention from many researchers in the last five year. There have been continuously new advancements and reports from areas of both natural products and organic synthesis. We have intensively studied the alkaloidal constituents of five Daphniphyllum plants and obtained over 40 Daphniphyllum alkaloids including 12 new ones. Of the new alkaloids, calycinumine A (1), angustimine (2) and logeracemin A (3) are with new carbon frameworks. With a unique spiro ring system, logeracemin A (3) represents the first dimeric alkaloid of this structural family and its absolute structure was determined via spectroscopic data, X-ray diffraction analysis and computational ECD calculation. Most excitingly, 3 exhibited significant anti-HIV activity with an IC50 of 4.5 ± 0.1 mM (SI = 6.2). This discovery was published in the top chemical journal J. Am. Chem. Soc., and represents a milestone work in the studies of Daphniphyllum alkaloids.

2. Discovery of novel macrolides as new type of immunosuppressants Khaya ivorensis is mainly distributed in the tropical countries of Africa, such as Cameroon, Angola, and Nigeria, and is also cultivated in the Southern provinces of China. Our current investigation of the non-polar fraction of the ethanolic extract of its stem bark has led to the isolation and identification of two novel macrolides, ivorenolides A (4) and B (5) with 18- and 17-memebered heterocycles, respectively. Compounds 4 and 5 both incorporate oxane and conjugated acetylene functionalities (rare in plant metaboites). The absolute configuration of 4 was established via spectroscopic methods, X-ray crystallography and total synthesis of its enantiomer, while that of 5 was elucidated through spectroscopic data and total synthesis of its four most likely stereoisomers. Our biological tests demonstrated that 4 and its enantiomer displayed decent inhibition against ConA induced murine T-cell and LPS induced murine B-cell proliferation. In addition, the selective indexes of 4 and its enantiomer are equivalent to or even better than those of the positive controls (CsA & PSA). These new outcomes were published in J. Am. Chem. Soc. and Org. Lett., respectively.

3. New advances in the study of Meliacious limonoids

The Meliacious plants are well-known for their rich limonoid constituents with diverse and complex structures, and some limonoids have been reported to possess antifeeding, antimalarial and neuroprotective activities. The limonoid structure family has always been a hot research topic in natural products field because of their abundant complex carbon frameworks and biological properties. There are 62 species and 12 varieties belonging to 15 genera distributed in the tropical and subtropical areas of China. On the basis of our previous brilliant research work of the Meliacious limonoids, we have devoted lots of efforts to the investigations on 20+ Meliacious plants in the last five years. This five-year program has returned nearly 400 compounds comprising >150 new ones and more than half of these isolates are limonoids. Different types of limonoids showed antimicrobial, potassium channel inhibitory and 11？-HSD1 inhibitory activities. The new representative structures with new architectures are shown in Figure 3, such as chukrasone B (7) with an unprecedented 16,19-dinorlimonoid skeleton and walsucochinoid A (9) with a novel highly rearranged and aromatized ring-D motif.

4. New advances in the study of terpenoid compounds
In addition to limonoids, the study of other terpenoid constituents from TCM is also our main research content. We have investigated the terpenoid compounds from a number of species of the Meliaceae, Myrtaceae, Euphorbiaceae and Chloranthaceae families, and this has proved to be a very rewarding program.
(a) Investigation of diterpenoids The chemical study of Aphanamixis grandifolia have returned four linear diterpenoids with new carbon skeleton, represented by aphadilactone C (12). The absolute structures of them were established on the basis of spectroscopic data, chemical degradation, fragment synthesis, and calculated ECD data. Our biological tests determined that compound 12 is a potent (IC50 = 0.46 ？M) and highly selective (SI >217) diacylglycerol O-acyltransferase-1 inhibitor, being the strongest natural DGAT-1 inhibitor up to date. Meanwhile, the four new diterpenoids also exhibited remarkable antimalarial activities against Plasmodium falciparum (IC50 0.12 to 1.35 ？M). Two new diterpenoids (e.g. 13) with a new rearranged ent-clerodane backbone were obtained and identified from the medicinal plant Croton laevigatus, with their absolute configurations being established via X-ray experiments. This is one of the few recent reports on diterpenoids with new frameworks. We have intensively studied the chemical constituents of four Trigonostemon species in the recent 5 years, and discovered over 40 daphnane-type diterpenoids. Some of these compounds showed decent cytotoxicities against two human tumor cell lines HL-60 and A-549. One of the representative structures is trigochilide B (14) that features a new 12-carbon fragment to form a novel macrolide functionality with three conjugated double bonds.
(b) Investigation of sesquiterpenoids Plants of the Chloranthaceae family are well-known for their medicinal values and secondary metabolites of lindenane-type sesquiterpenoids and corresponding dimers. Our current work of Chloranthus serratus, a TCM, has reported for the first time two new-skeleton sesquiterpenoid dimer (e.g. 15) derived from an elemane and a eudesmane. The absolute structures of them were characterized via spectroscopic data, X-ray diffraction analyses, and calculated ECD data. We have obtained three sesquiterpenoid derivatives with mixed biogenesis from Eucalyptus globulus of the Myrtaceae family. Eucalyptin A (16) is the representative compound with new a carbon framework. All of the three meroterpenoids showed significant inhibition against HGF/c-Met axis which is a hot cancer target of recent years, representing a new class of c-Met inhibitors. Preliminary structure-activity relationship study revealed that neither separate sesquiterpenoid nor mere simple phloroglucinol derivative showed inhibitory effect, demonstrating that the coupling of the two structural units are necessary for their activities.  

Prof. Yue is the associate editor or editorial board member of four professional journals, Natural Products and Bioprospecting, Journal of Chinese Pharmaceutical Sciences, Journal of Asian Natural Products Research, and Chinese Journal of Natural Medicines.

2010 The first prize of Shanghai Municipal Award in natural science
2013 The second prize of State Natural Science Award

1.Cui-Ping Liu, Cheng-Ying Xie, Jin-Xin Zhao, Kai-Long Ji, Xin-Xiang Lei, Han Sun, Li-Guang Lou, and Jian-Min Yue*, Dysoxylactam A: A Macrocyclolipopeptide Reverses PGlycoproteinMediated Multidrug Resistance in Cancer Cells, Journal of the American Chemical Society, 2019, 141(17), 6812-6816.

2.Jin-Xin Zhao, Sha-Sha Wang, Xin-Hua Gao, Li Sheng, Jia Li, and Jian-Min Yue*, Structural Elucidation and Bio-inspired Total Syntheses of Ascorbylated Diterpenoid Hongkonoids A-D, Journal of the American Chemical Society, 2018, 140(7), 2485-2492.

3.Yao-Yue Fan, Hua Zhang, Yu Zhou, Hong-Bing Liu, Wei Tang, Bin Zhou, Jian-Ping Zuo, Jian-Min Yue*，Phainanoids A–F, A New Class of Potent Immunosuppressive Triterpenoids with an Unprecedented Carbon Skeleton from Phyllanthus hainanensis, Journal of the American Chemical Society, 2015, 137(1), 138-141.

4.Jin-Biao Xu, Hua Zhang, Li-She Gan, Ying-Shan Han, Mark A Wainberg, and Jian-Min Yue*, Logeracemin A, an Anti-HIV Daphniphyllum Alkaloid Dimer with a New Carbon Skeleton from Daphniphyllum longeracemosum, Journal of the American Chemical Society, 2014, 136(21), 7631-7633.

5.Bo Zhang, Yao Wang, Sheng-Ping Yang, Yu Zhou, Wen-Bin Wu, Tang Wei, Jian-Ping Zuo, Ying Li* and Jian-Min Yue*, Ivorenolide A, an Unprecedented Immunosuppressive Macrolide from Khaya ivorensis: Structural Elucidation and Bioinspired Total Synthesis, Journal of the American Chemical Society 2012, 134(51), 20605-20608.

6.Fan, Yao-Yue; Shi, Shu-Qin; Deng, Guo-Zhen; Liu, Hong-Chun; Xu, Cheng-Hui; Ding, Jian; Wang, Guan-Wu; Yue, Jian-Min*, Crokonoids A-C, A Highly Rearranged and Dual-Bridged Spiro Diterpenoid and Two Other Diterpenoids from Croton kongensis. Organic Letters, 2020, 22(3), 929-933.

7.Xu-Xin Zhu, Yao-Yue Fan, Li Sheng, Qun-Fang Liu, Jing-Ya Li, Jia Li*, Kun Gao*, and Jian-Min Yue*, Alstonlarsines A–D, Four Rearranged Indole Alkaloids from Alstonia scholaris, Organic Letters, 2019, 21(5), 1471-1474.

8.Yu-Hao Ren, Qun-Fang Liu, Li Chen, Shi-Jun He, Jian-Ping Zuo, Yao-Yue Fan*, and Jian-Min Yue*, Urceoloids A and B, Two C19 Steroids with a Rearranged Spirocyclic Carbon Skeleton from Urceola quintaretii, Organic Letters, 2019, 21(6), 1904–1907.

9.Xin-Hua Gao, Yao-Yue Fan, Qun-Fang Liu, Sang-Hyun Cho, Guido F. Pauli, Shao-Nong Chen, and Jian-Min Yue*, Organic Letters, 2019, 21(17), 7065–7068.

10.Xin-Hua Gao, Yan-Sheng Xu, Yao-Yue Fan, Li-She Gan, Jian-Ping Zuo*, and Jian-Min Yue*, Cascarinoids A C, A Class of Diterpenoid Alkaloids with Unpredicted Conformations from Croton cascarilloides, Organic Letters, 2018, 20(1), 228-231.

11.Wei-Yi Zhang, Jin-Xin Zhao, Li Sheng, Yao-Yue Fan, Jing-Ya Li, Kun Gao*, and Jian-Min Yue*, Mangelonoids A and B, Two Pairs of Macrocyclic Diterpenoid Enantiomers from Croton mangelong, Organic Letters, 2018, 20(13), 4040-4043.

12.Yao-Yue Fan, Yi-Li Sun, Bin Zhou, Jin-Xin Zhao, Li Sheng, Jing-Ya Li*, and Jian-Min Yue*，Hedyorienoids A and B, Two Sesquiterpenoid Dimers Featuring Different Polycyclic Skeletons from Hedyosmum orientale, Organic Letters, 2018, 20(17), 5435-5438.

13.Bin Zhou, Qun-Fang Liu, Seema Dalal, Maria B. Cassera, and Jian-Min Yue*, Fortunoids A–C, Three Sesquiterpenoid Dimers with Different Carbon Skeletons from Chloranthus fortunei. Organic Letters, 2017, 19(3), 734–737.

14.Guo-Cai Wang, Yao-Yue Fan, Sajan L. Shyaula, and Jian-Min Yue*, Triconoids A-D, Four Limonoids Possess Two Rearranged Carbon Skeletons from Trichilia connaroides. Organic Letters, 2017, 19(8), 2182–2185.

15.Yao-Yue Fan, Li-She Gan, Hong-Chun Liu, Heng Li, Cheng-Hui Xu, Jian-Ping Zuo, Jian Ding*, and Jian-Min Yue*, Phainanolide A, Highly Modified and Oxygenated Triterpenoid from Phyllanthus hainanensis. Organic Letters, 2017, 19(17), 4580–4583.

16.Jin-Hai Yu, Qun-Fang Liu, Li Sheng, Guo-Cai Wang, Jia Li and Jian-Min Yue*, Cipacinoids A–D, Four Limonoids with Spirocyclic Skeletons from Cipadessa cinerascens, Organic Letters, 2016, 18(3), 444-447.

17.Cui-Ping Liu, Guo-Cai Wang, Li-She Gan, Cheng-Hui Xu, Qun-Fang Liu, Jian Ding, and Jian-Min Yue*, Ciliatonoids A and B, Two Limonoids from Toona ciliata, Organic Letters, 2016, 18(12), 2894-2897.

18.Gang Ni, Hua Zhang, Yao-Yue Fan, Hong-Chun Liu, Jian Ding, and Jian-Min Yue*, Mannolides A–C with an Intact Diterpenoid Skeleton Providing Insights on the Biosynthesis of Antitumor Cephalotaxus Troponoids, Organic Letters, 2016, 18(8), 1880-1883.

19.Hua Zhang, Sajan L. Shyaula, Jing-Ya Li, Jia Li, and Jian-Min Yue*, Himalensines A and B, Alkaloids with Unprecedented Carbon Skeletons from Daphniphyllum himalense, Organic Letters, 2016, 18(5), 1202-1205.

20.Hua Zhang, Kong-Kai Zhu, Yin-Shan Han, Cheng Luo, Mark A. Wainberg, and Jian-Min Yue*, Flueggether A and Virosinine A, Anti-HIV Alkaloids from Flueggea virosa, Organic Letters, 2015, 17, 6274-6277.

21.Jin-Biao Xu, Yao-Yue Fan, Li-She Gan, Yu-Bo Zhou, Jia Li, and Jian-Min Yue*, Cephalotanins A?D, Four Norditerpenoids Represent Three Highly Rigid Carbon Skeletons from Cephalotaxus sinensis, Chemistry - A European Journal, 2016, 22(41), 14648–14654.

22.Kai-Long Ji, Yao-Yue Fan, Zhan-Peng Ge, Li Sheng, You-Kai Xu, Li-She Gan, Jing-Ya Li, and Jian-Min Yue*, Maximumins A-D, Rearranged Labdane-Type Diterpenoids with Four Different Carbon Skeletons from Amomum maximum, Journal of Organic Chemistry, 2019, 84(1), 282–288.

23.Wei-Yan Qi, Jin-Xin Zhao, Yan Wu, Kun Gao*, Jian-Min Yue*, Quorumolides A-C, Three Novel Cembranoids from Euphorbia antiquorum, Journal of Organic Chemistry, 2018, 83(2), 1041-1045.

24.Jin-Xin Zhao, Cui-Ping Liu, Meng-Meng Zhang, Jia Li and Jian-Min Yue*, Dysohonin A, a Meroditerpenoid Incorporating a 6,15,6-Fused Heterotricyclic Ring System from Dysoxylum hongkongense, Organic Chemistry Frontiers, 2018, 5, 2202-2207.

25.Jiao-Jiao Cui, Kai-Long Ji, Hong-Chun Liu, Bin Zhou, Qun-Fang Liu, Cheng-Hui Xu, Jian Ding, Jin-Xin Zhao,* and Jian-Min Yue*, Cytotoxic Tigliane Diterpenoids from Croton damayeshu, Journal of Natural Products, 2019, 82(6), 1550-1557.

26.Zhan-Peng Ge, Hong-Chun Liu, Guo-Cai Wang, Qun-Fang Liu, Cheng-Hui Xu, Jian Ding, Yao-Yue Fan*, and Jian-Min Yue*, Journal of Natural Products, 2019, 82(6), 1565-1575.

27.Yao-Yue Fan, Jin-Biao Xu, Hong-Chun Liu, Li-She Gan, Jian Ding, and Jian-Min Yue*, Cephanolides A–J, Cephalotane-Type Diterpenoids from Cephalotaxus sinensis, Journal of Natural Products, 2017, 80(12), 3159-3166.

28.Bin Zhou, Yan Wu, Seema Dalal, Emilio F. Merino, Qun-Fang Liu, Cheng-Hui Xu, Tao Yuan, Jian Ding, David G. I. Kingston, Maria B. Cassera, and Jian-Min Yue*, Nanomolar Antimalarial Agents against Chloroquine-Resistant Plasmodium falciparum from Medicinal Plants and their Structure-Activity Relationships，Journal of Natural Products, 2017, 80(1), 96-107.

29.Yang Yu, Li-She Gan, Sheng-Ping Yang, Li Sheng, Qun-Fang Liu, Shao-Nong Chen, Jia Li,* Jian-Min Yue*, Eucarobustols A-I, Conjugates of Sesquiterpenoids and Acylphloroglucinols from Eucalyptus robusta, Journal of Natural Products, 2016, 79(5), 1365-1372.

30.Guo-Cai Wang, Jin-Hai Yu, Yu Shen, Ying Leng, Hua Zhang,* and Jian-Min Yue*, Limonoids and Triterpenoids as 11 -HSD1 Inhibitors from Walsura robusta, Journal of Natural Products, 2016, 79(4), 899-906.