Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (9): 2840-2849.DOI: 10.6023/cjoc202204035 Previous Articles     Next Articles

ARTICLES

浅蓝霉素H的发酵优化与浅蓝苷K的化学合成

罗云a, 高谕康a, 燕鹏程a, 朱伟明a,b,c,*()   

  1. a 中国海洋大学医药学院 海洋药物教育部重点实验室 山东青岛 266003
    b 中国科学院上海有机化学研究所 天然产物有机合成化学重点实验室 上海 200032
    c 青岛海洋科学与技术试点国家实验室 海洋药物与生物制品功能实验室 山东青岛 266237
  • 收稿日期:2022-04-14 修回日期:2022-06-06 发布日期:2022-06-16
  • 通讯作者: 朱伟明
  • 基金资助:
    国家自然科学基金委员会-山东省人民政府联合基金(U1906213); 天然产物有机合成化学院重点实验室开放基金(SIOC-2021-7)

Fermentation Optimization of the Caerulomycin H and the Synthesis of Cyanogriside K

Yun Luoa, Yukang Gaoa, Pengcheng Yana, Weiming Zhua,b,c()   

  1. a Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong 266003
    b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
    c Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, Shandong 266237
  • Received:2022-04-14 Revised:2022-06-06 Published:2022-06-16
  • Contact: Weiming Zhu
  • Supported by:
    National Natural Science Foundation of China-Shandong Union Foundation(U1906213); Open Fund Projects from Key Laboratory of Synthetic Chemistry of Natural Substances(SIOC-2021-7)

Caerulomycin H (2) and its 4-yl α-L-rhamnopyranoside [cyanogriside K (1)] are two microbial natural products from marine-derived Actinoalloteichus cyanogriseus WH1-2216-6. Cyanogriside K (1) shows good antiproliferative activity against tumor cells, whereas the yield is very low and the synthesis has not been reported. Thus, enough caerulomycin H (2) was first obtained by optimazing the fermentation condition of the mutant strain CRM05 of A. cyanogriseus WH1-2216-6. The yield of caerulomycin H (2) reached 272 mg/L (increased by 5 times) in the optimal solid medium consisted of corn pellets (80 g) and liqiud medium 5# for actinomycetes (100 mL). Then cyanogriside K (1) was synthesized with 25.6% total yield from caerulomycin H (2) by six steps reactions including deoximation, rhamnosylation, oximation and deacetylation. The structure of cyanogriside K (1) was identified by NMR, HRESIMS and specific rotation data. It is the same compound as the reported natural product. Furthermore, cyanogriside K (1) showed good bioactivity against the proliferation of the tumor cell lines PATU8988T, 786-O, 5673, DU145, A-375, FaDu and SF126, with the half maximal inhibitory concentration (IC50) values ranging from 1.07 μmol/L to 1.78 μmol/L.

Key words: caerulomycin H, fermentation optimization, rhamnosylation, cyanogriside K, antiproliferation