Sulcatol, synthesis

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). 

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. 

Figure 5. Synthesis of (S)-sulcatol and (2R,5S)-pityol. Reagents a) DHPf TsOH (quant.) b) LAH/ether (89%) c) TsC1/C5H5N (quant.) d) Me2C=CHMgBr, Cul/THF (quant.) e) AcOH-THF-H2Of A (82%) f) Tl(0Ac)3/HBF4-An-H20 (99% 12% after MPLC purification).

In the area of pheromone synthesis, oxymercuration-oxidative demercuration has also proven valuable. For example, all four stereoisomers (rf tetrahydro-2,2,6-trimethyi-2//-pyran-3-ol, from the eim bark beetle Pteleobius vittatus have been acquired by a sequence from (/ )- and (S)-sulcatol, which incorporates this mercury chemistry. The epimeric alcohols (47) and (48 Scheme 37) were separable (MPLC)... 

On the other hand, resolution of racemic a-halo carboxylic acids (93) with butanol can be effected with lipase (Table 7 and equation 35). Applications of enzyme-catalyzed acyl transfer reactions, among many others, are the synthesis of the pheromone (5)-sulcatol (95 equation 36) and of (/ )-glycidylbu-... 

The natural product (R)-sulcatol is a male-produced aggregation pheromone of the ambrosia beetle. This insect can devastate entire forests when its population is out of control.Various studies revealed that different species respond to the compound in different enantiomeric excess. The asymmetric synthesis of (R)-sulcatol was accomplished in the laboratory of S.G. Davies using a stereospecific [2,3]-Meisenheimer rearrangement as the key step. The treatment of the allylic amine substrate with mCPBA followed by the filtration of the reaction mixture through deactivated basic alumina afforded the desired hydroxylamine as a single diastereomer. 

Fig. 6. Epoxidation of a (S)-sulcatol derivative by the fungus A. niger. Synthesis of the biologically active pheromone pityol [112]...

Figure 4.51 Synthesis of the enantiomers of sulcatol (1). Modified by permission of Shokabo Publishing Co., Ltd...

RC(=0)—0(CHn)H, n = 4, 5]. Baker s yeast has been used in many synthetic applications. Hydroxyester (599), for example, was used in Mori s synthesis of (5)-(-t-)-sulcatol. 9 More complex systems can be reduced, as in the reduction of 602 to 603 (88% yield and >99% ee). 20 -phe selectivity is consistent with the (5)-selectivity predicted by Prelog s Rule. 1,3-Diketones are usually reduced to the p-keto alcohol. 2,4-Hexanedione, for example, was reduced to (5)-5-hydroxy-3-hexanone quantitatively [>99% ee]. 2l... 

Reaction of 147 with the mixed cuprate of 3-methy 1-2-butene gives, in one step, (/ )-( — )-sulcatol (148) the enantiomer of an aggregation pheromone of a wood-boring ambrosia beetle [53]. Oxirane 147 has also been instrumental in the synthesis of (2S, 5/ )-2-methyl-5-hex-anolide (151), one of the antipodes of the sex pheromone of the carpenter bee [54] (Scheme 22) and the macrolide fungal metabolite (7 )-recifeiolide (155) [55] (Scheme 23). 

Oxirane 40 has been used in the synthesis of a variety of natural products, such as (5)-( + )-sulcatol (319), the aggregation pheromone of a wood-boring ambrosia beetle [53], and (2R,... 

An initial feeling for these alternatives can be gained by discussion of the synthesis of sulcatol (Scheme 10.1), a pheromone of a noxious insect. The... 

Bond-set (iii) in Scheme 10.2 for the synthesis of sulcatol could be realized with an umpoled synthon, applying Hoppe s carbamate procedure [5] (Scheme 10.4). 

Scheme 10.5 Potential chiral precursors for a synthesis of sulcatol...

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