Sulcatol

Fpobtem Suggest a synthesis of optically active S-(+)-sulcatol (13), the aggregation pheromone of the wood-boring ambrosia beetle, from available ethyl (S)-(-)-lactate (14). 

By synthesizing pure enantiomers of pheromones, various stereochemistry-pheromone activity relationships could be clarified. For example, in the case of sulcatol (6-methyl-5-hepten-2-ol),both the enantiomers are necessary for bioactivity. For other relationships, please refer to [4-9]. 

Fluorinated analogues of (/ )-(—)-sulcatol and of frontalin, which are aggregative pheromones of wood destructive insects have been prepared by means of chiral sulfoxides (Figures 4.40 and 4.41). ... 

The situation is summarized from a slightly different perspective in Figure 2.2. Here, data obtained using the same set of organic solvents have been plotted. The porcine pancreatic lipase-catalyzed transesterification of sulcatol (6-methyl-5-hepten-2-ol) with butyric acid trifluoroethyl ester [81] has been chosen (arbitrarily) to calibrate the solvents. It is clear that, irrespective of the solvent descriptors that one may aim to investigate, different systems are seen to respond differently to the same (change of) medium. 

A generous gift of 3-propyl-l,2-dithiolane and of ipsenol was received from D. Wackerchuck (Phero Tech, Inc.). J.H. Borden and L. Chong (Simon Fraser University) contributed a sample of sulcatol. 

Methyl-5-hepten-2-one is a valuable precursor for microbial epoxidations and hence the production of chiral ethers with high optical purities. The biotransformation of 6-methyl-5-hepten-2-one (33) by Botryodiplodia malorum CBS 13450 to (/ )-sulcatol (84) was described [61], which is then epoxidised to the (55)-epoxide (85) and opened intramolecularly to cis-(2R,5R)-2-(2 -hydroxyisopropyl)-5-methyltetra-hydrofuran (86) and c/s-(35,67 )-3-hydroxy-2,2,6-trimethyltetrahydropyran (87). Reduction of 6-methyl-5-hepten-2-one (33) with baker s yeast to (5)-sulcatol (88) which was used as substrate for Kloeckera corticis... 

Comparable results were also reported by another group [65]. Controlled conversion of 6-methyl-5-hepten-2-one by Botrytis cinerea resulted in the formation of (5)-(+)-6-methyl-5-hepten-2-ol (sulcatol) of 90% ee. In addition, (2R,5R), (25,55)-, (2R,5S) and (25,5/ )-pityol and the four enantiomers of 3-hydroxy-2,2,6-trimethyltetrahydropyran were found as biotransformation products of 6-methyl-5-hepten-2-one. 

Similarly, enantiomerically pure hydrophobic (S)-l-phenyl-2-propanol, (S)-4-phe-nyl-2-butanol, and (S)-6-methylhept-5-en-2-ol (sulcatol) were obtained with high purities in a dual-loop enzyme membrane reactor unit with separate membrane extraction unit (Kruse, 1996). Whereas substrate concentrations were low at 9-12 mM, space-time yields higher than 100 g (L d) 1 as well as concentrated product solutions were obtained. 

Borden J. H., Chong L., McLean J. A., Slessor K. N. and Mori K. (1976) Gnathotrichus sulcatus synergistic response to enantiomers of the aggregation pheromone sulcatol. Science 192, 894—896. 

Byrne K. J., Swigar A. A., Silverstein R. M., Borden J. H. and Stokkink E. (1974) Sulcatol population aggregation pheromone in the scolytid beetle, Gnathotrichus sulcatus. J. Insect Physiol. 20, 1895-1900. 

Mori K. and Puapoomchareon P. (1987) Conversion of the enantiomers of sulcatol (6-methyl-5-hepten-2-ol) to the enantiomers of pityol [fra s-2-(l-hydroxy-1-methylethyl)-5-methyltetrahydrofuran], a male-specific attractant of the bark beetle Pityophthorus pityographus. Liebigs Annalen der Chemie 3, 271-272. 

In the same way, 6-methyl-5-hepten-2-one (entry 2) can conveniently be converted into 6-methyl-5-hepten-2-ol (sulcatol), which in its (R) configuration is an insect pheromone. 

The use of 2-propanol for these substrates, besides its role as hydrogen source, allows suppression of cydization reactions promoted by the acidity of the catalyst. Nevertheless, when cydization leads to valuable products, as in the case of 3,3,5-trimethylpyran derived from sulcatol, it is possible to steer the reaction in this direction by using molecular hydrogen and a hydrocarbon solvent [27]. 

A population aggregation pheromone has been identified from males of the scolytid, Gnathotrichus sulcatus (69). A 65/35 mixture of the (S)-(+) and the (R)-(-) enantiomers of 6-methyl-5-hepten-2-ol (sulcatol) was isolated from the boring dust and shown to attract both females and males in a ratio of 2.65 1, respectively. 

This method, employing methylation by Mel, was used to synthesise pheromones such as (S)-sulcatol 416.176 The oxazolidinone protecting group features a safety-catch which is released by treatment with acid intramolecular assistance to hydrolysis of the secondary amide 415 rapidly generates the free alcohol product 416. 

Another insect pheromone synthesis illustrates one of the drawbacks of chiral pool approaches. The ambrosia beetle aggregation pheromone is called sulcatol and is a simple secondary alcohol. This pheromone poses a rather unusual synthetic problem the beetles produce it as a 65 35 mixture of enantiomers so, in order to mimic the pheromone s effect, the chemist has to synthesize both enantiomers separately and mix them together in the right proportion. 

S)-Sulcatol cannot be made by this route, because the L-sugar is unavailable (even D-deoxyri-bose is quite expensive), so an alternative synthesis was needed that could be adapted to give either isomer. The solution is to go back to another hydroxy-acid, ethyl lactate, which is more widely available as its (5)-enantiomer, but which can be converted simply to either enantiomer of a key epoxide intermediate. From (S)-ethyl lactate, protection of the alcohol, reduction of the ester, and tosylation allows ring closure to one enantiomer of the epoxide tosylation of the secondary hydroxyl group followed by reduction and ring closure gives the other enantiomer. 

For this reason, the two enantiomers of propylene oxide are commonly used as chiral pool starting materials. These epoxides react with the appropriate Giignard reagent to give either enantiomer of the sulcatol. 

Ethyl 3-Hydroxybutanoate as a Building Block for Sulcatol and Pityol. 

Gnathotrichus retusus. This was synthesized in 73% overall yield from (S)-15 as shown in Figure 5 (13,18). Sulcatol (16) was... 

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