Total Synthesis, structure revision and antifungal activity of palmarumycin B8 and B7

Leichuan Xu; Haoyun Ma; Xinkun An; Tingting Zhang; Daowan Lai; Ligang Zhou; Mingan Wang

doi:10.1016/j.bioorg.2024.107479

Total Synthesis, structure revision and antifungal activity of palmarumycin B₈ and B₇

Bioorg Chem. 2024 Jul:148:107479. doi: 10.1016/j.bioorg.2024.107479. Epub 2024 May 19.

Authors

Leichuan Xu¹, Haoyun Ma², Xinkun An³, Tingting Zhang⁴, Daowan Lai⁵, Ligang Zhou⁶, Mingan Wang⁷

Affiliations

¹ Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, People's Republic of China; Hebei Shengxue Dacheng Pharmaceutical Co., Ltd., Luancheng District 051432, Hebei Province, People's Republic of China. Electronic address: xuleichuan@163.com.
² Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, People's Republic of China. Electronic address: haoyunma1618@163.com.
³ Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, People's Republic of China. Electronic address: s20213101997@cau.edu.cn.
⁴ Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, People's Republic of China. Electronic address: tengteng@cau.edu.cn.
⁵ Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, People's Republic of China. Electronic address: dwlai@cau.edu.cn.
⁶ Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, People's Republic of China. Electronic address: lgzhou@cau.edu.cn.
⁷ Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, People's Republic of China. Electronic address: wangma@cau.edu.cn.

PMID: 38772292
DOI: 10.1016/j.bioorg.2024.107479

Abstract

Palmarymycins B₈ (1), its regioisomer (2) and B₇ (3) were synthesized via 10-, 9-, and 11-steps in 6.5 %, 2.3 % and 0.54 % overall yields from chroman-4-one (4), 4-hydroxyindanone (12), and 2,5-dimethoxybenzaldehyde (20) as the starting materials, using benzyl protection, enol trimethylsilyl ether by TMSOTf, Rubottom oxidation and deprotection with hydrogenation under Pd/C catalyst as the key steps, respectively. Their structures were characterized by ¹H, ¹³C NMR, COSY, HSQC, HMBC and HR-ESI-MS spectral data. The structure of palmarumycin B₈ was revised from 1 to 2 based on the total synthesis, 2D NMR analysis and DFT calculation. The antifungal assay results indicated that palmarumycin B₈ (1) showed moderate inhibitory activity against Phytophthora capsica. Compounds 15 and 16 exhibited excellent in vitro antifungal activities against P. capsica with EC₅₀ values of 2.17 and 8.50 μg/mL, respectively.

Keywords: Antifungal activity; DFT calculation; Palmarumycin B(7) and B(8); Structure revision; Total synthesis.

MeSH terms

Antifungal Agents* / chemical synthesis
Antifungal Agents* / chemistry
Antifungal Agents* / pharmacology
Density Functional Theory
Dose-Response Relationship, Drug
Microbial Sensitivity Tests*
Molecular Structure
Structure-Activity Relationship

Substances

Antifungal Agents