Stereoselective Synthesis of a Bicyclic Norsesquiterpene Backbone – A Possible Route to Nardosinane Derivatives

Abstract

We have developed an efficient diastereoselective synthetic route towards a nardosinane sesquiterpene scaffold. The strategy used a key bicyclic diene intermediate 11a, and allowed access to valuable polyoxygenated sesquiterpenes 21 and 22, which may be regarded as analogues of the natural sesquiterpenes laevinol B and fulvol acetate, respectively.

(1R,2S,4S,4aS,8S,8aS)-4-Hydroxy-8,8a-dimethyl-10-oxo-2,3,4,7,8,8a-hexahydro-1H-4a,1-(epoxymethano)naphthalen-2-yl acetate

“…For the synthesis, see: Selaimia-Ferdjani et al (2013). For the biological activity of the natural lactone Paralemnolide A analogue of the title compound, see: Wang et al (2012) and of related nardosinane sesquiterpene derivatives, see: Bishara et al (2008); Huang et al (2011); Petit et al (2004); Lu et al (2011).…”

“…Title compound was synthesized according to the reported method (Selaimia-Ferdjani et al, 2013): To a solution of diene 1 (100 mg, 0.38 mmol) in CH 2 Cl 2 (2.5 ml) at 0°C was added via cannula a solution of mCPBA (350 mg, 0.38 mmol) in CH 2 Cl 2 (5.0 ml). After 20 min, the reaction mixture was quenched with saturated NaHCO 3 solution (10 ml).…”

Total Synthesis of (−)-Lamellodysidine A via an Intramolecular Diels–Alder Reaction

“…The synthesis of 5 was envisioned by introducing a γ-lactone ring to ester 6 via a Wittig reaction. Compound 7 , which is accessible in two steps from ( R )-(−)-carvone, an inexpensive material from the chiral pool, was anticipated to provide 6 in one step.…”

“…Wittig reaction. Compound 7, which is accessible in two steps from (R)-(−)-carvone, 4 an inexpensive material from the chiral pool, was anticipated to provide 6 in one step.…”

Unexpected Alkene Isomerization during Iterative Cross-Coupling To Form Hindered, Electron-Deficient Trienes

“…This class includes the eremophilane skeleton (>1300 natural products, approximately) and nardosinane skeleton (>160 natural products), represented by nootkatone ( 4 ), periconianone F ( 5 ), and flavalin E ( 6 ) . While the syntheses of individual members of this family have been reported and creative synthetic strategies beyond the often-used Robinson annulation have been advanced, the construction of the dimethyl decalin core 1 stereoselectively still poses a challenge, and new synthetic approaches would be of significant value. − …”