Formal Asymmetric Synthesis of Pentalenolactone E and Pentalenolactone F-2. Construction of the Angular Diquinanoid δ-Lactone

Abstract

A formal asymmetric synthesis of pentalenolactone E (1b) and pentalenolactone F (1a) has been accomplished. Ozonolysis of the diphenyl‐substituted triquinane 3 and Kauffmann methylenation of ketone 5 with WOCl3‐2 MeLi yielded the unsubstituted triquinane 9. The crucial rearrangement of the linear triquinanoid lactone 11 to the angular triquinanoid lactone 14a was accomplished using orthoformate and acid in methanol. Subjecting triquinanes 14a/b to the selenoxide method gave triquinene 15. Homologation of γ‐lactone 15 to the angular diquinanoid δ‐lactone 2 via a Horner‐Wadsworth‐Emmons or Peterson reaction of hemiacetals 16a/b was, however, not successful. Chemoselective reduction of 14a afforded hemiacetals 21a/b, reaction of which with the phosphonate salt 17a ultimately led to the ketene dithioacetal 22. The angular intermediates 25a/b were obtained from 22 by reduction to give the linear hemiacetals 24a/b, which rearranged to the dithio ortholactones 25a/b in the presence of acid. Introduction of the double bond and deprotection were accomplished via selenation of 25a/b with N,N‐diethylbenzeneselenylamide and treatment of selenides 30a/b with silver nitrate. The unsaturated aldehydes 28 and 29 thus obtained were converted to 2 and 31, respectively, by oxidation with manganese dioxide in the presence of sodium cyanide, methanol and acetic acid. Alkene 2 was isolated by crystallization.

Regiospecific 6-Endo-Annulation of in Situ Generated 3,4-Dienamides/Acids: Synthesis of δ-Lactams and δ-Lactones

“…α-Alkylidene δ-lactones and δ-lactams are special subclasses of δ-lactone/δ-lactam derivatives with a characteristic exoalkylidene moiety conjugated with a carbonyl group, the distinct feature believed to be crucial for their biological activities . α-Alkylidene δ-lactones have been identified in a variety of natural products (Crassin, Artemisitene, Teucrium Lactone,Pentalenolactone E, etc.) (Figure ).…”

Natural sesquiterpenoids

“…178 A formal and asymmetric synthesis of pentalenolactone E and pentalenolactone F has been achieved. 179,180 An efficient preparation of racemic pentalenene has been reported. 181 The total synthesis of (±)-tremulenolide A and (±)-tremulenediol A has been described.…”

Enantiospecific Approach toward Pentalenolactone

“…Notwithstanding this, only two research groups have addressed the issue of optical purity in the synthesis of (−)-pentalenolactone E methyl ester ( 2 ) by an enzymatic resolution of an advanced synthetic intermediate. , However, to the best of our knowledge, no general enantiospecific approach toward the synthesis of this quaternary carbon-centered polycyclic structure has yet been reported. In light of these considerations, we were prompted to devise a simple means for building the pentalenolactone quinane skeleton in an enantiospecific form.…”