Jiquilpane Hydrocarbon Skeleton Generated by Two Successive Wagner−Meerwein Rearrangements of Longipinane Derivatives

Abstract

The molecular rearrangement of (1R,3S,4S,5S,7S,8R,9S,10R,11R)-7,8,9-triacetyloxylongipinan-1-ol (4) under acidic conditions afforded (1S,4R,5R,7S,8R,9S,10S)-7,8,9-triacetyloxyuruap-3(12)-ene (5), while 6, the C(3)-stereoisomer of 4, after two consecutive Wagner-Meerwein rearrangements followed by two 1,2-hydride migrations, afforded (4R,5R,7S,8S,9S,10S,11S)-7,8,9-triacetyloxyjiquilp-3(12)-ene (7), which possesses a new hydrocarbon skeleton. The structures of the new substances were elucidated by 1D and 2D NMR data in combination with X-ray diffraction analyses of the uruapane, longipinane, and jiquilpane derivatives 5, 6, and 14, respectively. Molecular modeling at the ab initio level was used to study the reaction mechanisms, while deuterium labeling was employed to confirm the C-C bond migrations and the hydride shifts.

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

“…The reaction mechanisms for the rearrangement of 2 into 10 and 11 (Schemes and ) are proposed in accordance with the extensive reports for terpenoid transformations, ,,− supporting the existence of 1,2-hydride shifts and retro-aldol cleavages. − For the formation of 10 (Scheme ), Lewis acid coordination at the C-9 angeloyloxy group of 2 induces migration of the antiperiplanar C-4–C-10 bond to form the C-4–C-9 bond. The carbocation at C-10, shown in A + , then undergoes a C-1–C-11 bond migration to form the C-1–C-10 bond, providing the C-11 cation B + , which is prone to form a tetrahydrofuran ring by attack of the C-13 hydroxy group.…”

“…(3R,4R,5S,6S,9R,11R)-13-Hydroxymoreli-10( 14)-en-1-one (7) 14.4, 5.6, 1.4 Hz, H-2α), 2.10 (1H, br s, H-4), 1.94 (1H, m, H-3), 1.82 (2H, m overlapped, H-8α and H-8β), 1.71 (1H, dd overlapped, J = 14.5, 12.6 Hz, H-2β), 1.77 (1H, d, J = 1.9 Hz, H-9), 1.41 (1H, m overlapped, H-7α), 1.37 (1H, dd overlapped, J = 7.1, 4.0 Hz, H-7β), 1.12 (3H, s, H-14), 1.08 (3H, s, H-12), 1.00 (3H, d, J = 6.6 Hz, H-15); 13 (4S,5R,6S,8S,10R)-10,13-Oxyneojiquilp-2-en-1-one (11). This compound is white prisms; mp 56−57 °C; [α] 589 +82, [α] 578 +86, [α] 546 +102, [α] 436 +234, [α] 365 +1086 (c 0.79, CHCl 3 ); UV (EtOH) λ max (log ε) 240 (2.94); IR (CHCl 3 ) ν max 2954, 2919, 2850, 1652, 1377, 1056 cm −1 ; 1 H NMR: δ 5.84 (1H, dq, J = 2.5, 1.4 Hz, H-2), 4.05 (1H, q, J = 6.8 Hz, H-10), 3.58 (1H, dd, J = 12.0, 2.7 Hz, H-13a), 3.49 (1H, ddd, J = 10.9, 5.0, 1.3 Hz, H-4), 3.41 (1H, dd, J = 12.0, 1.5 Hz, H-13b), 2.52 (1H, dd, J = 16.0, 3.2 Hz, H-11α), 2.24 (1H, dd overlapped, J = 16.0, 14.1 Hz, H-11β), 2.19 (1H, ddd overlapped, J = 6.4, 5.0, 2.5 Hz, H-9α), 1.94 (3H, t, J = 1.4 Hz, H-15), 1.85 (1H, dddd, J = 12.8, 3.1, 2.8, 0.9 Hz, H-7α), 1.75 (1H, br quintet, J = 3.4 Hz, H-8), 1.67 (1H, dddd, J = 14.1, 10.9, 3.2, 1.3 Hz, H-5), 1.53 (1H, ddd, J = 12.9, 3.8, 3.4 Hz, H-9β), 1.34 (1H, dddd overlapped, J = 12.8, 3.1, 2.8, 0.9 Hz, H-7β), 1.29 (3H, d, J = 6.8 Hz, H-14), 0.73 (3H, s, H-12); 13 Single-Crystal X-ray Diffraction Studies.…”

“…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. − …”

“…The C-13 angelate group of 1 was selectively removed by a controlled alkaline hydrolysis 3 using KOH in MeOH at room temperature to afford 2, while the total alkaline hydrolysis 2 of 1 using KOH in MeOH under reflux yielded 3. Treatment of 2 with boron trifluoride etherate in CH 2 Cl 2 at 40 °C for 3 h afforded the two rearranged products, (3R,4R,5R,6S,9R,10S,11S)-11,13-oxyneomorelian-1-one (10), obtained in 46% yield, and (4S,5R,6S,8S,10R)-10,13-oxyneojiquilp-2-en-1-one (11), obtained in 29% yield. In contrast, treatment of 3 with boron trifluoride etherate in CH 2 Cl 2 at 40 °C for 2 h afforded 10 (43%) and (3R,4R,5S,6S,9R,11R)-13-hydroxymoreli-10(14)en-1-one (7) (48%).…”

Regioselective Oxidation of (+)-.ALPHA.-Longipinene by Aspergillus niger

“…In predious paper, conformation of the cycloheptane ring in longipinenes was investegated, which has four main conformations of the cycloheptane ring [11][12][13] . When there is a hydroxyl group of the C-5 position in a or b configuration, it is presumptively determined that the compound has different conformation each by chemical shift of 13 , d C 215.8 ppm (C)). About the 1 H NMR evidence for the presence of two methyl group.…”