Synthesis of (+)-8-deoxyvernolepin and its 11,13-dihydroderivative. A novel reaction initiated by sulfene elimination leads to the 2-Oxa-cis-decalin skeleton.
The title compounds are interesting candidates for antifungal screening. This paper describes the enantiospecific synthesis of these compounds starting from (+)-costunolide isolated from a commercially available extract. We used two novel reactions as key synthetic steps in this work: the acid-induced cyclization of an delta,epsilon-epoxy ester, which stereoselectively gave a hydroxymethyl-substituted delta-lactone, with the hydroxyalkyl group in the desired beta-equatorial disposition, and a reaction cascade, initiated by a base-promoted sulfene elimination, which led to a 10-oxiranyl-2-oxa-cis-decalin from the mesylate of a trans-fused delta-lactone. We also found that the reaction between selenium dioxide and the 1,5-diene system of elemanolides gave selenadecalins analogous to natural eudesmanolides. Our results prove that the synthetic strategy employed, on the basis of biomimetic concepts, is a useful procedure for the enantiospecific preparation of (+)-vernolepin-related compounds from accessible germacrolides.
Barrero
Alejandro F
AF
Department of Organic Chemistry, Faculty of Sciences, University of Granada, Campus Fuentenueva s/n, E-18071 Granada, Spain. afbarre@goliat.ugr.es
Oltra
J Enrique
JE
Alvarez
Míriam
M
Rosales
Antonio
A
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D007202:Indicators and Reagents; D008968:Molecular Conformation; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013416:Sulfamerazine
D000935:Antifungal Agents; D007202:Indicators and Reagents; D012717:Sesquiterpenes; C013921:deoxyvernolepin; C012049:sulfaperine; D013416:Sulfamerazine