Convergent biomimetic semisynthesis of disesquiterpenoid rumphellolide J

Abstract

The convergent biomimetic gram-scale synthesis of disesquiterpenoid ester rumphellolide J is described. 4β,8β-Epoxycaryophyllan-5-ol was prepared in 67% yield (1.4 g) from naturally ambudant (–)-β-caryophyllene. (+)-Rumphellaoic acid A was obtained in...

Semisynthesis of Linariophyllenes A–C and Rumphellolide H, Structure Revisions and Proposed Biosynthesis Pathways

“…1 The synthesis of linariophyllene C (proposed structure 3) (Scheme 2) started from β-caryophyllene oxide (6) by LDAmediated isomerization to allylic alcohol 15. 4,15,16 Compound 15 was subjected to vanadium(IV)-catalyzed epoxidation in the presence of tBuOOH to obtain epoxyalcohol 16 as the only detectable diastereomer, reproducing the literature results. 17 The 1,1-disubstituted epoxide 16 is preorganized for the intramolecular alcohol attack on the epoxide in an S N 2 reaction and was converted to cis-trisubstituted epoxide 17 via Payne rearrangement in basic media.…”

“…Synthesis. (1R,4R,6R,9S,10S)-9-Hydroxymethyl-4,12,12-trimethyl-5-oxatricyclo[8.2.0.0 4,6 ]dodecane-9-ol (7). (−)-β-Caryophyllene oxide ((6), 15.4 g; 69.8 mmol) was dissolved in an acetone (630 mL) and H 2 O (70 mL) mixture.…”

“…Synthesis and characterization data were described in our previous paper. 4 Diisopropylamine (3.85 mL; 27.5 mmol) was dissolved in anhydrous tetrahydrofuran (THF, 70 mL), and the solution was cooled to 0 °C. A solution (2.0 M) of nBuLi in hexanes (13.7 mL, 27.5 mmol) was added dropwise to the mixture.…”

“…1 H NMR (400 MHz, CDCl 3 , δ): 4.87 (dd, J = 1.7, 0.8 Hz, 1H), 4.83 (d, J = 1.5 Hz, 1H), 3.78 (dd, J = 12.2, 4.8 Hz, 1H), 3.51 (dd, J = 12.2, 8.0 Hz, 1H), 2.98 (ddd, J = 11.0, 3.6, 1.1 Hz, 1H), 2.49 (q, J = 8.9 Hz, 1H), 2.39−2.18 (m, 3H), 2.00−1.94 (m, 1H), 1.93−1.80 (m, 2H), 1.76 (dd, J = 8.2, 5.0 Hz, 1H), 1.62−1.48 (m, 3H), 1.47−1.35 (m, 2H), 1.04 (s, 3H), 0.99 (s, 3H). 13 ((1R,4R,6R,10S)-12,12-Dimethyl-9-methylene-5-oxatricyclo-[8.2.0.0 4,6 ]dodecan-4-yl)methyl methanesulfonate (18). Epoxyalcohol 17 (1.38 g; 5.85 mmol) and Et 3 N (5.71 mL; 41.0 mmol) were dissolved in CH 2 Cl 2 (60 mL).…”

“…((1R,4S,6R,9S,10S)-9-Hydroxy-4,12,12-trimethyl-5-oxatricyclo-[8.2.0.0 4,6 ]dodecan-9-yl)methyl acetate (20) and ((1R,2S,5R,8S,9S)-8-Hydroxy-4,4,8-trimethyl-12-oxatricyclo[7.2.1.0 2,5 ]dodecan-1-yl)methyl acetate (21). 20 and 21 were isolated after the aforementioned dihydroxylation and acetylation sequence of isocaryophyllene-4S,5R-oxide (19).…”