Linalool chirality

In recent years, there is only one example of a pheromone in solitary Apocrita being chemically identified. Chiral GC and chiral GC-EAD provided identification of (3S)-(+)-linalool 8 >99.9% e.e. as a mandibular gland mate attractant in both males and females of Colletes cunicularius. Male contact with a scented source could be initiated with 5 ng per lure (3S)-(+)-linalool, which may act as both a sex attractant and a food attractant [35]. 

Bernreuther A, Schreier P, Multidimensional gas chromatography-mass spectrometry A powerful tool for the direct chiral evaluation of aroma compounds in plant tissues, II, Linalool in essential oils and fruits PhytochemAnall. G7— 7(), 1991. 

Schubert V, Mosandl A, Chiral compounds of essential oils, VIII Stereodifferentiation of linalool using multidimensional gas chromatography, Phytochem Anal 2 171-174, 1991. 

Using a chiral column, coated with a definite modified cyclodextrin as the chiral stationary phase, the elution orders of furanoid and pyranoid linalool oxides are not comparable [11, 12]. Consistently, the chromatographic behaviour of diastereomers and/or enantiomers on modified cyclodextrins is not predictable (Fig. 17.1, Table 17.1). Even by changing the non-chiral polysiloxane part of the chiral stationary phase used, the order of elution may significantly be changed [13]. The reliable assignment of the elution order in enantio-cGC implies the coinjection of structurally well defined references [11-13]. 

Table 17.1 Elution order of the furanoid linalool oxides using different modified cyclodextrins (CD) as chiral stationary phases [11, 13]...

Fig. 17.14 Simultaneous stereoanalysis of Lavandula oil constituents, using enantio-MDGC (standard mixture), a Preseparation of racemic compounds unresolved enantiomeric pairs of octan-3-ol (6, 7), frcms-linalool oxide (1, 2), oct-l-en-3-ol (9, 10), ds-linalool oxide (3, 4), camphor (5, 8), linalool (17, 18), linalyl acetate (11, 12), terpinen-4-ol (15, 16) and lavandulol (13, 14). b Chiral resolution of enantiomeric pairs, transferred from the precolumn trans-linalool oxide 1 (2S,5S), 2 (2R,5R) ds-linalool oxide 3 (2R,5S), 4 (2S,5R) camphor 5 (IS), 8 (IR) octan-3-ol 6 R, 7S oct-1-en-3-ol PS, 10 R linalyl acetate 11 R, 12 S lavandulol 13 R, 14 S terpinen-4-ol 15 R, 16 S linalool 17 R, 18 S. [75]...

Hener U, Braunsdorf R, Kreis P, Dietrich A, Maas B, Euler E, Schlag B, Mosandl A (1992) Chiral compounds of essential oils X The role of linalool in the origin evaluation of essential oils. Chem Mikrobiol Technol Lebensm 14 129... 

The synthesis of tetrahydrofurans through cyclization via epoxide ring opening has been well investigated and has been applied to the preparation of a-bisabolol oxides (69IJC1060) and linalool oxides (77H(6)1365) and by Kishi et al. in the synthesis of lasalocid A (195), where the epoxide pathway resulted in a stereospecific construction of six out of the ten chiral centers (Scheme 93) (78JA2933). 

It has long been known that appropriately substituted [2.2]paracyclophanes are chiral, chemically stable and do not racemize under normal reaction conditions. With these seemingly ideal prerequisites for use in chiral synthesis, it is perhaps surprising that only three examples have appeared in the literature, all of them in recent years (Scheme 8). Reich employed [2.2]paracyclo-phane-derived selenides such as 24 to administer chirality transfer in selenoxide [2,3] sigmatropic rearrangements. Using this methodology, he was able to synthesize optically active linalool 25... 

Oxidation of the chiral (4-geranylseleno)-15-(4-toluenesulfonyl)[2.2]paracyclophane with 3-chloroperbenzoic acid gave (S )-linalool with 67% enantioselectivity39. Diethylamine was added before warming up to avoid side reactions by the generated selenic acid. On the basis of similar oxidation of paracyclophane-substituted alkyl selenides it was assumed that the asymmetric induction in the oxidation step is responsible for the modest selectivity. 

The asymmetric [2,3]sigmatropic rearrangement of several other allyl aryl selenides has been reported, but only moderate selectivities are observed [27] (Scheme 18). The oxidation of cinnamyl and geranyl selenides derived from L-prolinol with MCPBA at -90°C afforded the chiral l-phenyl-2-propen-l-ol and linalool with moderate enantiomeric excess, respectively. 

Solvolysis of (S)-2,6-dimethyloct-5-yl toluene-p-sulphonate gives a tetrahydro-linalool, (i )-2,6-dimethyloctan-6-ol, with about 60% retention of asymmetry. Kirmse and Arold have described several other similar reactions and suggest that a hydrophobic anchimeric interference of alkyl residues persists during the rearrangement, giving chirality to the carbonium ion. ... 

Linalool and linalyl acetate are the intensively studied chiral monoterpenoids. Their enantiomeric ratio had been investigated in the precious bergamot oil [36-38], lavender oils [39], and many other plants used as fragrance and flavour materials mainly fi-om Labiatae and Rutaceae families [40-42]. 

Adulteration of the oil with racemic, synthetic linalool may be detected using chiral gas chromatography, as studies showed the natural enantiomeric ratio of linalool to be as follows (R)-(-)-linalool (11-15%) (S)-(-H)-linalool (85-89%) [80]. 

Chirality evaluation of linalyl acetate and linalool have been introduced as new and substantial criteria in the authenticity control of lavender oils. In particular, linalyl acetate from genuine lavender oils has high enantiomeric purity favouring the R-configuration, irrespective of the Lavandula species, and storage or work-up conditions [32]. Using 2,3-di-0-acylated-6-0-silylated cyclodextrins as a new generation of chiral stationary phases in enantio-cGC, most of chiral compounds of Lavandula oil, are stereoanalyzed simultaneously (Fig. 6.37 Fig. 6.38). 

Investigations on authentic essential oils of Lavandula species are summarized in Table 6.20, detecting the chiral monoterpenoids with high enantiomeric purities as characteristic constituents of genuine lavender oils Besides R-linalyl acetate (11) and R-linalool (17), the chiral main compounds of genuine lavender oils 2R-trans-(2), 2R-cis-(3)-linalool oxide (fur.), (R)-lavandulol (13), as well as S-terpinen-4-ol (16) are detected [111]. 

Steam distillation (30 min) corresponds with good manufacturing practice (GMP) in the processing of lavender oil and is without any influence on the genuine chirality of linalool, as to conclude by comparison with the results on linalool enantiomeric ratio from the diethyl ether extraction. 

Also, the addition of copper plates in order to simulate the application of cupric vessels during lavender oil production does not influence the chiral stability of linalool and linalyl acetate. 

Nevertheless, under the conditions of good manufacturing practice (GMP) the chirality evaluation of linalool has proved to be a reliable indicator in the authenticity control of lavender, bergamot, and orange oils. This fact will be of considerable importance in the quality assurance for the flavour and fragrance industry. 

If to extend these experiences to the chirality evaluation of linalool from other natural substrates, generally attention must be paid to the GMP-condi-tions as well as to the pH-values of the substrates investigated. 

Comparative investigations on the enantiomeric purity of linalool and linalyl acetate in the essential oils of Lavandula angustrfolia MILLER leads to quick and simple techniques of gas chromatographic chirality evaluation of lavender oil compounds. Their usefulness in the authenticity control of lavender oil compounds is demonstrated in Lig. 6.39 [95]. 

The most interesting conversions of geraniol to linalool would be those introducing chirality in the linalool. This can be effected by using chiral auxiliaries during allylic epoxidation of geraniol. Allylic epoxidation of geraniol is efficiently carried out with tert-butyl hydroperoxide in presence of aluminum tri-tert-... 

Attention is drawn to the synthesis the oxygenated linalool oxide 896. This compound (and other stereoisomers) is not a naturally occurring monoterpenoid, but a fragment required in the synthesis of a calcium ion-selective ionophore, ionomycin, and was made from hydroxygeranyl acetate (113, R = Ac), then Sharpless conditions for introducing a chiral epoxide were used. The vital step is the cyclization of 897 by epoxidizing again under Sharpless conditions (titanium tetraisopropoxide and diethyl tartrate) when the product 896 is obtained. ... 

A simple heterocyclic acid needed for an anti-HIV drug A chiral pool synthesis from aspartic acid Choosing a new reaction to solve the stereochemistry problem Making the new reaction asymmetric Part III - Grandisol and Some Bicyclo[3.2.0]Heptan-2-Ols A bicyclic insect attractant used in agriculture Chiral Pool Syntheses from Other Terpenes An attempt from linalool... 

This subject has recently been reviewed6 and we shall concentrate on the different approaches to grandisol outlined in that review. Many of these approaches can clearly be used for the other compounds. An early approach was a chiral pool strategy from the simpler and commercially available terpene (R)-( (-linalool 38. Though this did not lead to a useful synthesis, it pointed the way to effective methods, particularly the Cu(I)-catalysed photochemical closure of the four-membered ring. 

Ionization of allylic systems, generating stabilized ions, is one of the most successful methods of inducing cyclization. On treating chiral linalool with protic acids, a 6-exo reaction takes place via a chairlike transition state (concerted mechanism) but the configuration is inverted on building chiral limonene (10)14. 

---