The first total synthesis and revision of absolute stereochemistry of natural cytotoxic lactone cleistanolate

Jelena Kesić; Ivana Kovačević; Mirjana Popsavin; Goran Benedeković; Marko V Rodić; Vesna Kojić; Velimir Popsavin

doi:10.1016/j.bioorg.2022.106073

The first total synthesis and revision of absolute stereochemistry of natural cytotoxic lactone cleistanolate

Bioorg Chem. 2022 Nov:128:106073. doi: 10.1016/j.bioorg.2022.106073. Epub 2022 Aug 3.

Authors

Jelena Kesić¹, Ivana Kovačević², Mirjana Popsavin¹, Goran Benedeković¹, Marko V Rodić¹, Vesna Kojić³, Velimir Popsavin⁴

Affiliations

¹ University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
² University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia. Electronic address: ivana.kovacevic@dh.uns.ac.rs.
³ University of Novi Sad, Faculty of Medicine, Oncology Institute of Vojvodina, put Dr. Goldmana 4, 21204 Sremska Kamenica, Serbia.
⁴ University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia; Serbian Academy of Sciences and Arts, Kneza Mihaila 35, 11000 Belgrade, Serbia.

PMID: 35939856
DOI: 10.1016/j.bioorg.2022.106073

Abstract

Development of a synthetic route applicable to d-ribose and d-xylose enabled the synthesis of cleistanolate putative structure, its five stereoisomers, and led to revision and confirmation of absolute stereochemistry of the natural product. Key steps of the synthesis included zinc-mediated THF ring-opening and stereoselective dihydroxylation under the Upjohn conditions. The first total synthesis of cleistanolate was completed in eight steps starting from d-xylose. The C-5 stereocenter of the natural product was assigned the correct (5S)-stereochemistry. Cytotoxicity of natural product was briefly investigated.

Keywords: Cleistanolate; Cytotoxicity; Natural products; Structure revision; Total synthesis.

Publication types

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

MeSH terms

Antineoplastic Agents*
Biological Products* / chemistry
Lactones / chemistry
Molecular Structure
Stereoisomerism
Xylose

Substances

Antineoplastic Agents
Biological Products
Lactones
Xylose