Highly Stereocontrolled Total Syntheses of Cedrane Sesquiterpenes via Cascade [5+2] Cycloaddition/Etherification

Abstract

Cedrane sesquiterpenes possess common tricyclo [5.3.1.0 1,5 ]undecane core structure. The varied oxa-five-membered ring decorating their core structure to form 8-oxa-tetracyclo[7.2.2.0 1,5 .0 6,13]tridecane framework, containing six consecutive chiral centers (including two all-carbon quaternary centers and one oxygenated quaternary carbon center), has proven to be a synthetic challenge and a biosynthetic mystery to date. Herein, we reported a distinct and biomimetic strategy to these sesquiterpenes resulting in the concise asymmetric total syntheses of three cedrane sesquiterpenes from simple commercially available building blocks. Key feature is exploitation of a cascade oxidative dearomatization-induced [5+2] cycloaddition/etherification to highly stereocontrolled construct 8-oxa-tetracyclo[7.2.2.0 1,5 .0 6,13]tridecane framework with five contiguous chiral centers in one step. In addition, a metal-free I 2 -catalyzed and DMSO-mediated oxidative dehydroaromatization was applied to prepare curcuphenol and its derivatives from the highly functionalized cyclohexenones with minimal manipulations.

Valorization of the Sabinas Forest Waste (Juniperus phoenicea and Juniperus thurifera) as Source of Biopesticides

“…40 The hexane extract J. thurifera (Jt-Hex) was column chromatographed on silica gel producing six main fractions. Subsequent esterifications and further separations of these fractions led to the isolation of seven compounds (Figure 3), five of them being sesquiterpenes (cedrol (3), 41 methyl hinokiate (10), widdrol (11), 42 8S-14-cedrandiol (13) 43 and 14, 44 and two of them diterpenes (methyl cis-communate (9) 40 and isocupresic acid (12)). 45 These compounds have been identified by analysis of their 1 H and 13 C-NMR spectra and by comparison of these data with those reported in the literature.…”

“…Compound 12: 1 H-NMR (400 MHz, CDCl 3 ): δ 5.41 (td, J = 7.0, 1.4 Hz, 1H), 4.88 (s, 1H), 4.55 (s, 1H), 4.18 (d, J = 6.9 Hz, 2H), 2.45-2.41 (m, 1H), 2.23-2.13 (m, 2H), 2.02-1.82 (m, 5H), 1.69 (s, 3H), 1.60-1.41 (m, 5H), 1.35 (dd, J = 12.0, 3.1 Hz, 1H), 1.26 (s, 3H), 1.08 (td, J = 13.5, 4.2 Hz, 2H), 0.63 (s, 3H). 13 45 Compound 13: 43 -Jt-Hex-F (MTBE) weighed 140 mg (4.0%). 15 mg of this fraction was subjected to semi-preparative HPLC using an isocratic elution (H-MTBE, 1-3) at a flow rate of 4 mL/min to give 8 mg of 13 and 2 mg of 14.…”

“…13 C-NMR (133 MHz, CDCl 3 ): δ 75.3, 69.1, 57.6, 53.8, 52.1, 49.5, 41.4, 41.1, 37.0, 35.5, 31.6, 30,9, 25.4, 23.8 15.6, according to bibliography. 43 - Jt-Hex-F (MTBE) weighed 140 mg (4.0%). 15 mg of this fraction was subjected to semi-preparative HPLC using an isocratic elution (H-MTBE, 1-3) at a flow rate of 4 mL/min to give 8 mg of 13 and 2 mg of 14 . Compound 14 : 1 H-NMR (400 MHz, CDCl 3 ): δ 4.41 (ddd, J = 9.6, 5.9, 2.3 Hz, 1H), 3.87 (d, J = 11.4 Hz, 1H), 3.52 (d, J = 11.5 Hz, 1H), 2.13 (ddd, J = 12.6, 9.5, 3.1 Hz, 1H), 2.03-1.94 (m, 1H), 1.88 (ddd, J = 14.3, 11.2, 8.1 Hz, 1H), 1.52-1.21 (m, 6H), 1.13 (dd, J = 12.5, 5.9 Hz, 1H), 1.06-0,97 (m, 1H), 0.96 (s, 3H), 0.95 (s, 3H), 0.85 (d, J = 7.2 Hz, 3H).…”

Total Syntheses of Uncommon C30 Terpenoids: Chamaecydin and Isochamaecydin

“…The “chiral pool” of terpenes has long served as a starting material in complex natural product synthesis. − As a program to use chiral terpenes as enantiopure starting materials in natural product synthesis, we previously reported the syntheses of biyouyanagin A, spirooliganones A and B, callistrilones A–E, psiguajdianone, and three cedrane sesquiterpenes from chiral terpenes zingiberene, sabiene, α-phellandrene, caryophyllene, and citronellal, respectively. A continuation of the investigation has resulted in the total syntheses of chamaecydin ( 1 ) and isochamaecydin ( 2 ) from sabinene, and reported herein are the details.…”