Total Synthesis of 4α,5α,10β-Trihydroxycadinane and Its C ₄-Isomer: ­Structural Revision of a Natural Sesquiterpenoid

Abstract

An efficient approach to cadinane sesquiterpenes starting from (R)-carvone, employing a ring closing metathesis (RCM) reaction and a modified allylic diazene rearrangement as key steps, is described. The first asymmetric total syntheses of 4α,5α,10β-trihydroxycadinane (1) and natural 4β,5α,10β-trihydroxycadinane (2) were accomplished and the structure of natural product A was revised to 2.

Key words

cadinane sesquiterpenes - synthesis - 4α,5α,10β-tri­hydroxycadinane - 4β,5α,10β-trihydroxycadinane

References and Notes

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14

Atomic coordinates for 16 have been deposited with Cambridge Crystallographic Data Centre under the deposition number CCDC no. 617500.

15

Spectral data of compound 1: [α]_D ²⁰ -16 (c = 0.1, CHCl₃). IR (film): 3415, 2963, 2931, 1458, 1380, 1117, 1019 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 3.63 (s, 1 H), 2.39 (br s, 1 H), 1.98-2.09 (m, 1 H), 1.82-1.66 (m, 3 H), 1.45-1.54 (m, 4 H), 1.29-1.40 (m, 5 H), 1.23 (s, 3 H), 1.18 (s, 3 H), 0.92 (d, J = 6.9 Hz, 3 H), 0.76 (d, J = 6.9 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 73.1, 72.5, 70.8, 42.5, 42.1, 40.2, 39.2, 33.2, 28.9, 25.6, 23.7, 22.6, 21.4, 19.0, 15.3. HRMS (ES): m/z [M + Na]⁺ calcd for C₁₅H₂₈NaO₃: 279.1931; found: 279.1942.

16

Spectral data of compound 2: mp 185-186 °C; [α]_D ²⁰ -10 (c = 0.2, CHCl₃). IR (film): 3406, 1372, 1154, 1020 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 3.60 (br s, 1 H), 2.01 (m, 1 H), 1.82 (m, 1 H), 1.63-1.74 (m, 3 H), 1.50-1.57 (m, 5 H), 1.31-1.43 (m, 5 H), 1.27 (s, 3 H), 1.20 (s, 3 H), 0.94 (d, J = 7.2 Hz, 3 H), 0.81 (d, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 73.0, 71.3, 70.8, 42.3, 41.8, 40.2, 37.4, 32.4, 28.7, 27.7, 25.6, 21.3, 20.1, 19.0, 15.4. HRMS (ES): m/z [M + Na]⁺ calcd for C₁₅H₂₈NaO₃: 279.1931; found: 279.1929.