1-Methoxyhexane-3-thiol, a Powerful Odorant of Clary Sage (Salvia sclarea L.)

Abstract

The peculiar and highly diffusive odor signal of flowering clary-sage plants (Salvia sclarea L.) was identified to derive from trace amounts of 1-methoxyhexane-3-thiol (1) by mass-spectrometry analysis and confirmed by comparison with synthetic racemic thiol (AE)-1. The enantiomers (S)-and (R)-1 were prepared by enantioselective synthesis, and the absolute configuration of (S)-1 was fully corroborated by X-ray-diffraction analysis of the crystalline thioester (1'S,1S)-2. Compound (S)-1 is one of the most powerful odorants known, with a detection threshold of 0.04 ¥ 10 À3 ng/l air, and is, with its herbaceous-green, alliaceous, and perspiration profile, key to the fragrance of clary-sage flowers and of the freshly distilled essential oil. As a consequence of its unique odor, 1 was also suspected to be part of the volatiles of a Ruta species where it was subsequently identified together with its homologue, 1-methoxyheptane-3-thiol (3), 1-methoxy-4-methylpentane-3-thiol (4), and the known 4-methoxy-2-methylbutane-2-thiol (5). The syntheses of (AE)-3 and (AE)-4 as well as of the enantiomer (R)-4 are described. In both natural fractions, the ratio (S)-1/(R)-1 was slightly in favor of the (S)-enantiomer. Natural 4 has (R)-configuration.1. Introduction. ± Clary-sage (Salvia sclarea L.) fields in full blossom elicit a peculiar olfactory signal, both intriguing and repulsive, somewhat reminiscent of human axillary perspiration, and very distinct from the array of odors known and available to a perfumer in industry. Always attracted by novel and original scents, we became interested in this highly unusual top note. In a recent monograph on sage oils [1], Boelens and Boelens state that −fresh plant material of Salvia sclarea has a strong, pungent and penetrating odor that is often disliked. This odor disappears during steam distillation and can not be recognized as the essential oil×. The monograph cites numerous references that report chemical and sensory evaluation of sage oils. Notably, Maurer and Hauser identified more than 250 chemical constituents in clary-sage oil (S. sclarea L.) [2a], but none of them is responsible for the pungent top notes [2b].Serendipity brought us into contact with local farmers who cultivate clary sage for essential-oil production. When gently rubbing the flower panicles on a hot summer evening prior to harvest, the odor signal was strong and unambiguously recognized. The aqueous forerun from steam distillation of freshly cut aerial plant material produced a fraction which allowed isolation and identification of the target compound, 1-methoxyhexane-3-thiol (1), after a series of focussed separation steps combined with mass spectrometry and comparison with synthetic reference materials.In this communication, we describe the isolation and identification of 1-methoxyhexane-3-thiol (1) as a new impact odorant from a steam distillate of S. sclarea L. The synthesis of racemic thiol (AE)-1 and its enantiomers is presented,

Preparation and Odour of Cis- and Trans-2-Methyltetrahydrofuran-3-Thiol Acetates

“…1 H NMR (CDCl 3 ) δ 1.68 (3H, d, J = 6.0 Hz, Me(5)), 3.05 (2H, d, J = 5.7 Hz, H-C(2)), 5.54 (2H, m, H-C(3) and C(4)), 10-12 (1H, br, -COOH). 13 C NMR (CDCl 3 ) δ 17.9 (Me), 37.8(C(2)), 121.9 (C(4)), 130.0 (C(3)), 179.0 (C(1)). 1 H NMR data were identical to those reported in the literature.…”

“…1 3)). 13 C NMR (CDCl 3 ) δ18.0 (Me), 35.9 (C(2)), 62.0 (C(1)), 127.2 (C(4)), 128.1 (C(3)). The 1 H NMR data were identical with those reported in the literature.…”

“…1 H NMR (CDCl 3 ) δ 1.64 (3H, d, J = 6.3 Hz, Me(C(5))), 2.39 (2H, q, J = 6.9 Hz, H-C(2)), 2.96 (3H, s, Me(mesyl)), 4.17 (2H, t, J = 6.9 Hz, H-C(1)), 5.36 (1H, m, H-C(4)), 5.57 (1H, m, H-C(3)). 13 C NMR (CDCl 3 ) δ 17.5 (Me(C(5)), 31.9 (C(2)), 36.8 (Me(mesyl)), 69.4 (C(1)), 124.5 (C(4)), 128.7 (C(3)). The 1 H NMR data corresponded with those reported in the literature.…”

“…1 H NMR (CDCl 3 ) δ 1.29 (3H, d, J = 6.0 Hz, Me), 2.28 (1H, m, H-C(4)), 2.56 (1H, m, H-C(4)), 3.65 (1H, m, H-C(3)), 3.88 (2H, m, H-C(5)), 4.07 (1H, m, H-C(2)). 13 C NMR (CDCl 3 ) δ 17.6 (Me), 24.9 (C(3)), 38.2 (C(4)), 66.8 (C(5)), 84.0 (C(2)). HRESIMS, m/z 212.97770 [M + H + ] (calcd for C 5 H 10 IO, 212.97708).…”

“…1 H NMR (CDCl 3 ) δ 1.33 (3H, d, J = 6.6 Hz, Me-C(2)), 2.34 (2H, m, H-C(4)), 3.05 (3H, s, Me(mesyl)), 3.80 (1H, td, J = 8.4, 5.4 Hz, H-C(5)), 4.08 (1H, q, J = 8.1 Hz, H-C(5)), 3.95 (1H, qd, J = 6.3, 3.6 Hz, H-C(2)), 5.13 (1H, ddd, J = 5.4, 3.6, 2.1 Hz, H-C(3)). 13 C NMR δ 14.4 (Me-C(2)), 34.0 (C(4)), 38.5 (Me(mesyl)), 65.8 (C(5)), 77.2 (C(2)), 81.9 (C(3)). HRESIMS, m/z 181.05317 [M + H + ] (calcd for C 6 H 13 O 4 S, 181.05291).…”