Molecular Rearrangement of Rastevione Mesylate into Arteagane Derivatives

Abstract

Molecular rearrangment of rastevione mesylate {!] in alkaline medium afforded two epimeric 2,6,6,11 -tetramethyltricyclo[5.4.0.04,8]undecane derivatives [2 and 3] by a 1,3-bond migration. Their stereostructures, which possess a new hydrocarbon skeleton named arteagane, were elucidated from nmr data in combination with X-ray diffraction analyses of 3 and its diacetate 7. The conformations of 2, 3, and several derivatives are reported.Molecular rearrangements of natural products offer the possibility of generating substances with novel skeletons (1-3) and increased understanding of their chemical behavior (4-6), which can be applied to synthetic approaches (7,8). In continuation of our research on molecular rearrangements of sesquiterpenes (9,10), we report herein the transformation of the longi^inene derivative rastevione mesylate [1] to the 2,6,6,11tetramethyltricyclo[5.4.0.0 ' Jundecane derivatives 2 and 3 by a 1,3-bond migration.

Novel Sesquiterpene Skeletons by Multiple Wagner–Meerwein Rearrangements of a Longipinane-1,9-diol Derivative

“…Their phytochemical studies started almost four decades ago with the structure elucidation of rastevione ( 1 ), which is easily available from the hexanes extracts of the roots of S. serrata . Since then, the longipinane skeleton has inspired the study of molecular rearrangements, − since it possesses a central strained four-membered ring simultaneously holding a six- and a seven-membered ring in 1,3 dispositions. The chemical exploration of these substances has led to the discovery of new carbocyclic scaffolds obtained through a series of molecular rearrangements promoted by the strategic location of functional groups on the tricyclic skeleton, which act as leaving groups when the four-membered ring strain is released.…”

Structure Determination and Mechanism of Formation of a seco-Moreliane Derivative Supported by Computational Analysis

“…The potential release of the annular strain conferred by the four-membered ring makes these compounds important substrates for the generation of new carbocyclic skeletons through molecular rearrangements (Figure ). So far, there have been nine new skeletons obtained by chemical (moreliane, arteagane, quirogane, jiquilpane, uruapane, meridane, and uladane) and photochemical (pingilonane and patzcuarane) pathways. The first molecular rearrangement carried out on a longipinane derivative led to the moreliane structure (Scheme ).…”

Novel Sesquiterpenoid Skeletons by Wagner–Meerwein Rearrangements of Longipinane-9,13-diol-1-one Derivatives

“…The organic layer was washed with H 2 O, dried over anhydrous Na 2 SO 4 , filtered, and evaporated to give a residue that was chromatographed over silica gel eluting with hexanes−EtOAc of increasing polarities. Compound 5 (55 mg, 94%) was obtained in the fractions eluted with a 3:2 mixture as a colorless oil: −30, [α] 365 −44 (c 1.0, CHCl 3 ); IR (CHCl 3 ) ν max 3602, 3017, 2948, 1720, 1374, 1255, 1036 cm −1 ; 1 H NMR: δ 4.88 (1H, t, J = 3.9 Hz, H-9), 4.27 (1H, dt, J = 9.2, 3.4 Hz, H-1), 3.83 (1H, d, J = 10.7 Hz, H-13a), 3.77 (1H, d, J = 10.7 Hz, H-13b), 2.46 (1H, t, J = 3.4 Hz, H-11), 2.37 (1H, m, H-3), 2.08 (3H, s, H-2′ Ac), 2.07 (3H, s, H-2″ Ac), 1.89 (2H, m, H-8α and H-8β), 1.84 (2H, m, H-2α and H-2β), 1.81 (1H, d overlapped, J = 3.4 Hz, H-4), 1.75 (1H, ddd, J = 14.6, 12.4, 5.0 Hz, H-7α), 1.22 (1H, dd, J = 14.6, 6.2 Hz, H-7β), 1.17 (1H, s, H-5), 1.11 (3H, s, H-14), 0.94 (3H, d, J = 6.9 Hz, H-15), 0.90 (3H, s, H-12); 13 (1S,3R,4S,5S,6S,9R,10R,11R)-13-Acetoxy-9,11-epoxyjiquilpane (6). A solution of 5 (50 mg) in CH 2 Cl 2 (2 mL) was treated with Et 2 O−BF 3 (0.5 mL).…”

“…For the preparation of 5, diol 3 was acetylated to provide 4, which was reduced using sodium borohydride in MeOH. Treatment of 5 with Et 2 O−BF 3 at room temperature for 24 h yielded (1S,3R,4S,5S,6S,9R,10R,11R)-13-acetoxy-9,11-epoxyjiquilpane (6) in 27% yield, together with several minor compounds that could not be characterized. In addition, an attempt to mesylate 3 directly afforded the rearranged product (3R,4R,5S,6S,9R,11R)-13-mesyloxymoreli-10( 14)-en-1-one (8) in 78% yield, while treatment of 1 with Et 2 O−BF 3 in CH 2 Cl 2 at 40 °C for 2 h generated (3R,4R,5S,6S,9R,11R)-13ageloyloxymoreli-10( 14)-en-1-one (9) in 80% yield.…”

“…It is known that the degree of functionalization and stereochemistry of the functional groups present in the longipinane skeleton are decisive in directing the rearrangements toward the six- or the seven-membered ring. This allows rearrangements in highly functionalized longipinanes to generate various novel skeletons and provide valuable information about their chemical behavior, which is very useful for the design of new synthetic strategies. − …”