Edouard Demole’s research while affiliated with Firmenich and other places

Two novel constituents of Burley tobacco condensate were shown to be 5-(4-methyl-2-furyl)-6-methylheptan-2-one (solanofuran, 4) and 3,4,7-trimethyl-1,6-dioxa-spiro[4.5]-dec-3-en-2-one (spiroxabovolide, 6). These structures were deduced from spectral data and confirmed by synthesis. Solanofuran (4) was prepared via the dye-sensitized photo-oxygenation of solanone (1). This type of reaction involving the uncommon ‘diene-addition’ of 1O2 to a conjugated acyclic diene system was thus applied for the first time to the synthesis of a terpenoid furan, a route that might have some biogenetic significance. Both solanofuran (4) and spiroxabovolide (6) display interesting organoleptic properties. Identification of these compounds increases to 210 the total number of Burley tobacco flavour constituents so far characterized in this laboratory.

1-p-Menthene-8-thiol (B) is shown to be a potent character-donating constituent of grapefruit juice, in which it occurs at the ppb-level or below. A convenient synthesis is described for this terpene-thiol, apparently the most powerful flavor compound ever found in nature.

The successful identification of damascenone (I) DORICENONE (trade mark of Firmenich & Cie, Geneva). and β‐damascone (III) DORINONE (trade mark of Firmenich & Cia, Geneva) in Burley tobacco oil was achieved through the use of an efficient vapour phase chromatography/mass spectrometry combination. Thus, the occurrence of β‐damascone in nature and the presence of damascenone in an essential oil not related to rose oil were demonstrated.

Investigation by gas liquid chromatography of a small but organoleptically typical subfraction of Oriental tobacco condensate led to the identification of 47 compounds. Of these 21 have hitherto not been reported as Oriental tobacco constituents, and 14 appear to be novel to all tobacco types. The latter are (E)-3-methyl-non-2-en-4-one (1), (E)-1-(2, 3, 6-trimethylphenyl)-but-2-en-1-one (3), pentadecan-15-olide (12), 8α, 13:9α, 13-diepoxy-15, 16-dinorlabdane (17), (Z)-octadec-9-en-18-olide (18), (E)-2-ethylidene-6, 10, 14-trimethylpentadecanal (21), the norlabdanoids 9, 10, 11, 14, 15, 16, tridecan-2-one, and 2-phenylethyl isovalerate. The macrolides 12 and 18 represent the first musk compounds detected in tobacco. Identification were made by direct comparison (MS. and/or 1 H-NMR./IR.) with the authentic chemicals synthesized whenever necessary.

Twelve novel constituents isolated from Burley tobacco condensate by semi-preparative GLC. have been identified as (E)-3,4-epoxy-5-isopropyl-nonane-2,8-dione (A), exo-(1-methyl-4-isopropyl-7,8-dioxabicyclo[3.2.1]oct-6-yl)methyl ketone (B), exo-1-(1-methyl-4-isopropyl-7,8-dioxabicyclo[3.2.1]oct-6-yl)-ethanol (C), (E)-5-isopropyl-8-hydroxy-8-methyl-non-6-en-2-one (D), (E)-5-isopropyl-6,7-epoxy-8-hydroxy-8-methyl-nonan-2-one (E), endo-2-(1-methyl-4-isopropyl-7,8-dioxabicyclo[3.2.1]oct-6-yl)-propan-2-ol (F), 3,3,5-trimethyl-8-isopropyl-4,9-dioxabicyclo[3.3.1]nonan-2-ol (G), (E)-5-isopropyl-non-3-ene-2,8-diol (H), 5-isopropyl-nonane-2,8-diol (I), (E)-5-isopropyl-8-hydroxy-non-6-en-2-one (J), 5-isopropyl-8-hydroxy-nonan-2-one (K), and (E)-3-isopropyl-6-methyl-hepta-4,6-dien-1-ol (L). Compounds A–K were synthesized from norsolanadione (2), and compound L from 2-isopropyl-5-oxo-hexanal (15). The relative configuration of the bicyclic internal acetals B, C, F, G and their δ-keto-epoxide precursors A and E is discussed. All these Burley tobacco flavour components belong to a growing family of metabolites structurally related to solanone (1). They are believed to arise from the breakdown of cembrene-type precursors.

Distillation foreruns from East Indian sandalwood oil (Santalum albumL.), representing 5–8% of the oil, have been investigated using fractional distillation, preparative column chromatography, gas liquid chromatography (GLC.), and chemical treatments. This allowed the isolation and characterization by their spectral data of 46 compounds. 32 of them were newly identified sandalwood oil constituents including 4 novel substances: santalone (2), 4-methylcyclohexa-1,3-dien-1-yl methyl ketone (4), 5,6-dimethyl-5-norbornen-exo-2-ol (7), and (E)-5-(2,3-dimethyl-3-nortricyclyl)-pent-3-en-2-one (20). The other constituents identified were 1-furfuryl-pyrrole (10) and 10 phenols accompanied by 17 terpene and sesquiterpene derivatives. Endo-2,endo-3-dimethyl-norbornan-exo-2-ol (6), an -santenol (z), precursor, was present in the last group of constituents. The compounds 2, 4, 6, 7, 20 have been synthesized as well as another novel constituent, endo-2-mythyl-3-methylidene-norbornan-exo-2-ol (5).

GLC. allowed the isolation of 1, 3, 6, 6-tetramethyl-5, 6, 7, 8-tetrahydro-isoquinolin-8-one (A) and 3,6,6-trimethyl-5,6-dihydro-7H-2-pyrindin-7-one (D) from Burley tobacco condensate (about 0.1% each). The structures and syntheses of these novel terpenoid alkaloids are described, and a possible way for their formation in tobacco is suggested.

The mixture obtained from the well-known BF3-catalyzed condensation of camphene and phenol contains at least nine terpeno-phenols. The major components are o- (p-) (2,2, exo-3-trimethyl-exo-5-norbornyl)-phenols, accompanied by some o- (p-) (exo-2-borny1)-phenols and smaller amounts of o- (p-) (1,3,3-trimethyl-exo-6-norborny1)- phenols. Further, very small amounts (>1%) of the three corresponding meta-substituted phenols also occur in the condensation mixture. On catalytic hydrogenation, these m-isomers lead to 3-terpenyl-cyclohexanols characterized by a powerful odour of sandalwood. Most surprisingly, the 2- and 4-terpenyl-cyclo-hexanols obtained in the same way from the o- and p-terpenyl-phenols are almost odourless. The sandalwood odour appears, therefore, to be highly characteristic of the 3-substituted cyclohexanols, and this fact has been conclusively verified by the unambiguous synthesis of the axial and equatorial epimers of 3-(2,2, exo-3-trimethyl-exo-5-norbornyl)-cyclohexanol.

Racemic methyl jasmonate (methyl cis-2-pent-2′-enyl-3-oxo-cyclopentylacétate), an odoriferous component of jasmine oil (Jasminum grandiflorum L.), has been synthesized. The synthesis of two related jasmine-like smelling keto-esters is also described.

Ambreinolide, sclareol-lactone and a pair of new trioxides C18H30O3 have been synthesized from suitable derivatives of (+)-manool through stereoselective reactions.