Synthesis of Mulinane Diterpenoids

Abstract

The mulinane class of diterpenoids is a set of tricyclic (5-6-7), biologically active natural products whose members exhibit a variety of oxidation states. Herein, we report the inaugural synthesis of four mulinanes employing a divergent approach that relies on a diastereoselective anionic oxy-Cope rearrangement to set the relative configuration of the C8 stereocenter and an unprecedented vinylogous Saegusa dehydrogenation reaction to address C-ring functionality.

7-6-5 Tricarbocyclic Diterpenes

“…Until 2009, cyathane syntheses have been collected in the excellent reviews of Wright and Whitehead [3] and Enquist and Stoltz [4]. Very recently, the first synthesis of 36, 43, 46, and 54 [186] mulinanes has been reported. This work reported the synthesis and synthetic approach concerning cyathane derivatives that have appeared later to 2009.…”

“…Guerrero Synthesis of Mulinanes 36,43,46,and 54 During the referee process, Guerrero and coworkers published the first synthesis of mulinane diterpenoids, specifically dienone 46 and dienes 54, 43, and 36 [186] (Scheme 5.18). In order to establish the relative configuration at C8, the authors used a diastereoselective anionic oxy-Cope rearrangement and an unprecedented vinylogous Saegusa dehydrogenation reaction to address C-ring functionality.…”

Mulinane- and Azorellane-Type Diterpenoids: A Systematic Review of Their Biosynthesis, Chemistry, and Pharmacology

“…Nearly all mulinanes are characterized by having a carboxyl group at the C-20 position and a functionalized seven-member ring. In contrast, in azorellanes C-20 is not functionalized but C-13 is usually oxygenated [ 11 , 12 ].…”

Mulinane and Azorellane Diterpenoid Biomarkers by GC-MS from a Representative Apiaceae (Umbelliferae) Species of the Andes

“…The biosynthetic pathway for the mulinane and azorellane diterpenoids has been proposed as starting from a phytatetraene [24]. Laboratory syntheses of polar mulinane diterpenoids have also recently been reported [36,37].…”