Total Synthesis of (−)‐13‐Oxyingenol and its Natural Derivative

Abstract

Ring functionalization: The total synthesis of a natural derivative of (−)‐13‐oxyingenol, a potent anti‐HIV diterpenoid, is reported. The key steps in this synthesis include a ring‐closing olefin metathesis and a Mislow–Evans‐type [2,3]‐sigmatropic rearrangement. This synthesis provides access to (−)‐13‐oxyingenol and its natural derivative in 21 steps from a synthetic intermediate previously prepared by Kigoshi and co‐workers.

Diastereoselective Total Synthesis of the Euphorbia Diterpenoid Pepluanol A: A Reductive Annulation Approach

“…Having rapidly assembled the [5,6,7] tricyclic skeleton, we turned to the late-stage synthesis of 2 (Scheme 4). Benefiting from the preferred boat transition state of 7,insitu generated dibromocarbene added exclusively to the less hindered convex face.U pon further reductive bismethylation, [23] the tetracycle 18 was formed in 44 %y ield.…”

Diastereoselective Total Synthesis of the Euphorbia Diterpenoid Pepluanol A: A Reductive Annulation Approach

“…[4] Thei ntriguing structures,a sw ell as important biological activities of Euphorbia diterpenoids, have stimulated numerous endeavors from the synthetic community,t hus leading to elegant syntheses of their core structures and target molecules. [5] Very recently,f urther investigation on extracts of the plant of E. peplus by Qiu and co-workers resulted in the discovery of three novel biogenetically related diterpenoids with effective inhibitory activity on the kv1.3 potassium channel, and they were subsequently named pepluacetal, penluanol A, and pepluanol B(1-3;F igure 1). [6] Structurally, 1-3 exhibit unprecedented [3,4,5,7], [ 3,5,6,7],a nd [3,5,5,8] tetracyclic ring systems,r espectively.T he unique polycyclic array with ahigh oxidation pattern, including the presence of six to eight stereogenic centers,m ake these molecules challenging synthetic prospects.I np articular, the commonly embedded pseudo-bicyclic 1,5-diol subunits prompted us to develop ag eneral and efficient approach for their rapid construction.…”

“…Different from the observation by Molander and co-workers, [7] ther eaction is not restricted to five-membered ring formation. Fore xample,t he cyclohexanol 5b was obtained in 88 %y ield as a1 .9:1 mixture of diastereomers.The double-bond geometry was found to have little influence on the cyclization,s ince both isomers of 4c were converted into 5c with as imilar yield and d.r.v alue.A series of diversely functionalized [5,6] and [6,6] bicyclic1 ,5diols (5d-g)w ere also constructed in excellent yields. Presumably,t he favored formation of the major diastereomers arises from the topographical bias of the conformationally fixed cyclic olefins.Furthermore,the 1,5-diols 5h-j,with differently sized bicyclicring systems,were produced as well, although the efficiencya nd diastereoselectivity gradually drops for longer tethers.…”