Harvest, After 50 Years of Sowing

Professor Han-Dong Sun was born in November 1939 in Baoshan city, Yunnan Province. Over the past five decades since his graduation from Yunnan University in 1962, he has been engaged in basic and applied research on the exploration of plant-derived medicines and natural perfumes, phytochemistry and drug development (Fig. 1). He was systematically engaged in the study on more than 260 species of resources and secondary metabolites in China, including those of the genus Isodon, the Taxaceae family, Schisandraceae family, Umbelliferae family, Lauraceae family, and lichens. His work has facilitated the studies on natural products isolated from the genus Isodon and the Schisandraceae family to an international leading level. The detailed studies are as follows:


Research on Natural Perfumes in Yunnan
The compound was successfully synthesized from a-pinene and possessed strong mosquito-and insect-repelling activities with no obvious side effects [1]. The project won the National Health Science Conference Award and the Second Prize of the Military Scientific Research Achievements in 1980. In the mid-1970s, in conjunction with Kunming Institute of Light Industry, they purified and synthesized nardostachnol acetate, a sesquiterpene with a persistent and intense aroma of sandalwood which is regarded an ideal raw material for rose-and fougere-type perfumes. The research provided a new sesquiterpene-based perfume for China, winning the First Prize of the Science and Technology Award of Kunming City and the Third Prize of the Scientific and Technological Progress Award of Yunnan Province in 1978 with the title ''A New Perfume, Nardostachnol Acetate''. Moreover, their study of Chinese angelica resulted in the widespread application of Chinese angelica in medicine and perfume, creating a market for the angelica and its inferior product in Yunnan. The discovery was awarded the Third Prize of the Scientific and Technological Progress Award of Yunnan Province in 1985.
From 1982 to 1992, Sun's group systematically probed into the aromatic and chemical constituents of 22 lichen species. They successfully developed two new lichen perfumery products, namely Chinese oakmoss No. 1 (with ethyl divaricatinate as the main aromatic component) and Chinese odour No. 2 (with ethyl haematommate and ethyl everninate as the main aromatic components) [2]. The aromas of these two products exhibited great similarities to those of French oakmoss products but are not identical. The perfumery project belonged to the National Ministry of

Research on Medicinal Plants Such as Taxaceae, Umbelliferae and Erigeron breviscapus
Since the US national Food and Drug Administration (FDA) approved Taxol as a drug for the treatment of ovarian cancer in 1992, it has been a subject of great interest for natural product chemists and pharmacists worldwide. Currently, Taxus brevifolia is not widely available in China, but an abundance of Taxaceae, such as Taxus yunnanensis and Taxus chinensis, could be found in Yunnan Province. Sun's group emphatically studied the aforementioned two plants obtained from different habitats jointly with Japanese researchers. Dr. Hong-Jie Zhang discovered a Taxol analog named taxuyunnanine ( Fig. 3) in the root of Taxus yunnanensis [7]. The analog exhibited cytotoxicity against KB cells with the same order of magnitude as that of Taxol. Dr. Bo Li derived the taxchinins, a series of novel diterpenoids, from the leaves of Taxus chinensis [8]. These systematic and in-depth investigations on Taxus yunnanensis and Taxus chinensis provided a solid scientific basis for the rational development, utilization and protection of Taxaceae species in Yunnan Province. Starting from 1974, Sun and his colleagues centered on the chemical constituents of Angelica apaensis, Heracleum rapula, and Heracleum scabridum, which are three plants of the Umbelliferae family. The results were released in ''Acta Botanica Yunnanica'', ''Chinese Traditional and Herbal Drugs'', and ''Bulletin of Botany'', respectively from 1975 to 1978 [9]. Later, Sun's group systematically explored the chemical constituents of more than 30 Umbelliferae species in southwest China. More than 300 compounds were purified and elucidated, among which more than 20 were reported for the first time, including apaensin, turgeniifolin A, and rubricauloside (Fig. 4), resulting in the publication of over 40 papers. These results not only increased the number of known chemical constituents and natural coumarins found in the Umbelliferae family but also clarified the association between their pharmacology and their chemical constituents. The research provided a scientific basis for the rational development and utilization of the Umbelliferae species. Of note, the project titled ''Studies on Chemical Constituents of 13 Umbelliferae Species'' won the Third Prize of the Natural Science Award of Yunnan Province in 1992.
Since the early 1990s, Sun and his group have spent more than 10 years studying on the bioactive constituents of Erigeron breviscapus, which is a well-known folk medicine for the treatment of cardiovascular and cerebrovascular diseases in Yunnan Province. In combination with biological screening, the previously reported compound, scutellarin, as well a variety of novel caffeoylquinic acid esters containing significant bioactivities were found, such as 3,5-dicaffeoylquinic acid and erigoster B (Fig. 4 Fig. 4 Representative chemical constitutes of Umbelliferae species and Erigeron breviscapus new compounds. For instance, a rare and highly oxygenated ent-kaurane C-glycoside, neoadenoloside A, was found from I. adenolomus; two spirolactone ent-kauranes with novel scaffolds, neolaxiflorins A and B were isolated from I. eriocalyx var. laxiflora, and a new diterpenoid-based macrolide possessing a unique 10-membered lactone ring was isolated from I. ternifolius. The above findings have provided more diverse frameworks and increased the chemical space for subsequent research on novel chemotherapeutics (Fig. 5) was selected as one of the ''Top Ten Progresses in Chinese Science'' in 2012 (Fig. 6).
Sun's group works closely with pharmacologists at home and abroad to investigate the anticancer properties of diterpenoids isolated from Isodon species, achieving dramatical breakthroughs. With the knowledge that oncotherapy is gradually moving towards target-based and individualized therapy, ent-kaurane diterpenoids have broad prospects in their application as anti-cancer drug candidates. Based on the previous research work, ''Donglingcao lozenges'' and ''Maoexiangchacai tablets'' have been successfully developed as antibacterial and antiinflammatory drugs that are particularly effective for upper respiratory tract infections. After being brought to market, they have proved economically rewarding and have created social benefits for years. One hundred and forty papers have been published concerning this project, 124 of which were published in SCI-listed journals. Seven patent applications have been submitted, and 5 of them have been granted. Two monographs, ''Diterpenoids from Isodon species'' and ''Chemistry of Diterpenoids'', have been completed.
The project has been awarded the ''Second Prize of Natural Science of Chinese Academy of Sciences'' in 1992 and the ''First Prize of Natural Science of Yunnan Province'' in 2002 and 2013 respectively.

Pioneering Research on Schinortriterpenoids
Schisandraceae is a family of important medicinal plant with two known genera, Schisandra and Kadsura. Our country possesses the most abundant sources of Schisandraceae species, and 21 of them can be used for medicinal purposes. For example, the dried mature fruits of S. chinensis have long been used in traditional Chinese medicine to enhance mental and physical working capacities and have been included in various editions of the Chinese pharmacopoeia. More than 50 years of prior studies on Schisandraceae species have revealed that their major secondary metabolites are dibenzocyclooctadiene lignans and lanostane-and cycloartane-type triterpenoids. Additionally, bifendate and bicyclol, two new anti-hepatitis drugs developed by Chinese scholars with independent intellectual property rights, have provided great economic and social benefits. However, owing to the previously insufficient research conditions, further investigations should be made about the chemical constituents of such group of important medicinal plants, the chemical basis underlying their medicinal uses, and the rational and sustainable exploitation and utilization of these abundant plant resources. Sun and colleagues have implemented systematic and in-depth research on the triterpenoids from 24 Schisandraceae species ever since early 1990s.
(1) Pioneering research on schinortriterpenoids (SNTs) The most significant achievement was the discovery of highly oxygenated schinortriterpenoids of the Schisandra species, characterized by polycyclicfused scaffolds containing numerous contiguous stereogenic centers (Fig. 7). These compounds have provided new clue for future development of pharmaceutical agents derived from the well-known traditional drug Schisandra chinensis and added important new dimensions to our understanding of triterpenoid chemistry. (2) The discovery of triterpenoids with novel skeletons from the Kadsura species two series of highly oxygenated triterpenoids possessing unusual ring systems and potent antitumor activities have been isolated from the genus Kadsura. The finding is a major breakthrough, which provides opportunities to identify new lead compounds and further investigate the genus. The discovery and synthesis of structurally novel and diverse SNTs has attracted the attention of natural product chemists, synthetic organic chemists and pharmacologists at home and abroad, and relevant studies have been cited in numerous reviews, textbooks and monographs. The work is an exemplary illustration of the research on the chemical constituents from one phytogroup. It has been recognized as one of the best achievements in natural product research by Chinese scholars who have become global leaders in the chemical studies of the Schisandraceae species.
In 2015, our group published a review on the latest research on the Schisandraceae triterpenoids in Natural Product Reports (NPR), in which the structural classifications, bioactivities, synthetic organic efforts, and the possible biogenetic pathways (Scheme 1)  were comprehensively depicted.
The systematic research on Schisandraceae triterpenoids is an original and symbolic research achievement made by Chinese natural product chemists that is recognized around the world. The research promotes the global academic status of Chinese natural product chemistry research and leads the development of phytochemistry and synthetic As of 2017, the group has published 760 papers in peerreviewed journals, including over 530 that were published in SCI-listed journals. Four monographs have been published, and 24 scientific research achievements received prizes from the Chinese Academy of Sciences, as well as from the state, provincial and ministerial level authorities. More than 70 doctoral and postgraduate students have been trained.
Since the implementation of Reform and Opening Up four decades ago, people have witnessed the rapid advancement of the Chinese economy. With strong support from the state and multilevel governments, the platform for natural product chemistry research in China has been substantially improved. Thanks to the efforts made by researchers, Chinese natural product chemistry research has transformed from the status of ''following'' as seen 40 years ago to a ''neck and neck'' position, even leading the way in particular fields. The abundance of plants and other natural product resources, in addition to the 2000-year history of the application of traditional Chinese medicine, is an inexhaustible gold mine for in-depth exploration. With continued clarification of our research directions and objectives, collaboration with other rapidly developing disciplines, consideration of national development needs and persistent research, I believe that we can make greater contributions and bring Chinese natural product chemistry research to a new golden era dominated by more fields. Based on the previous prospective results, I hope that our research group will broaden the horizons and keep pace with the development of modern natural product chemistry to supplement our achievements and finally contribute to the realization of the ''new age'' in our country.
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Scheme 1 Proposed major biogenetic pathway, classifications, and distributions of schinortriterpenoids