Total Synthesis of Leptochartamides A and B: Two Enantiomeric Pairs of Hydroxybenzyl Dimers from a Deep-Sea Fungus Leptosphaerulina chartarum

Meimei Cheng; Xuechao Cui; Yu Tang; Zongze Shao; Xiupian Liu; Juncheng Su; Jian Zhang; Qi Wang; Guoqiang Li

doi:10.1021/acs.joc.2c01347

Total Synthesis of Leptochartamides A and B: Two Enantiomeric Pairs of Hydroxybenzyl Dimers from a Deep-Sea Fungus Leptosphaerulina chartarum

J Org Chem. 2022 Aug 19;87(16):11090-11096. doi: 10.1021/acs.joc.2c01347. Epub 2022 Aug 3.

Authors

Meimei Cheng^{1

2

3}, Xuechao Cui^{1

4}, Yu Tang^{1

4}, Zongze Shao⁵, Xiupian Liu⁵, Juncheng Su⁶, Jian Zhang⁶, Qi Wang⁷, Guoqiang Li^{1

2}

Affiliations

¹ Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.
² Laboratory of Marine Drugs and Biological Products, Pilot National Laboratory for Marine Science and Technology, Qingdao 266235, People's Republic of China.
³ Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, People's Republic of China.
⁴ Laboratory for Marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, People's Republic of China.
⁵ Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Xiamen 361005, People's Republic of China.
⁶ State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, People's Republic of China.
⁷ Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao University, Qingdao 266021, People's Republic of China.

PMID: 35921599
DOI: 10.1021/acs.joc.2c01347

Abstract

Leptochartamides A and B (±1 and ±2), two pairs of enantiomeric hybrids with the same cyclo-bridged skeleton containing an unusual dioxa-azabicyclo[3.2.1]octane core system, were isolated from the deep-sea-derived fungus Leptosphaerulina chartarum. Their structures were determined by detailed spectroscopic analysis, single-crystal X-ray diffraction, electronic circular dichroism calculations, and the total synthesis. Compounds 2a and 2b showed selective cytotoxicity against Ewings sarcoma cells A673, with IC₅₀ values of 8.98 ± 0.23 and 4.18 ± 0.27 μM, respectively. The colony formation assay of compounds 2a and 2b against A673 cells was completed.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ascomycota* / chemistry
Circular Dichroism
Crystallography, X-Ray
Molecular Structure
Stereoisomerism

Supplementary concepts

Pithomyces chartarum