Natural product synthesis disparlure

This catalytic epoxidation method has been applied to the synthesis of a variety of natural products, particularly polyhydioxylated compounds, including carbohydrates (54) and macrolides. In addition, this reaction has been used for commercial synthesis of disparlure, a gypsy moth pheromone [J. T. Baker Co. (55) and the Shanghai Institute for Organic Chemistry (56)], and more importantly, glycidol, a versatile intermediate for synthesis of /3-blockers and other functionalized chiral molecules (Arco Co.) (Scheme 23) (57). 

The radicals may dimerize, participate in mixed coupling between two different radicals, or undergo cyclization. Each of these avenues is illustrated by the examples discussed next. Simple dimerization allows retrosynthetic disconnections to be made at any symmetrical carbon-carbon bond in a target molecule, and has been used in, for example, the synthesis of onocerin (13) [5], a- and )6-oconceradiene (14 and 15) [6], and pentacyclosqualene (16) [6,7]. The use of a mixed Kolbe oxidation allows disconnections to be made at nonsymmetrically substituted sites. A host of natural products have been generated using the latter protocol including, for example, brevicomin (21) [8], looplure (29) [9], and disparlure (35) [10] [note Scheme 2, Eq. (6), and Scheme 3]. 

The synthesis of disparlure (135) represents yet another fine example for the high potential of enamine-catalyzed a-functionalizations of aldehydes in the synthesis of natural products. The enantiomer (+)-135 is a sex pheromone of the female gypsy... 

Several applications of this reagent are known in the literature toward the synthesis of several natural products/templates such as erthyrosphingolipids 15S> (Hertweck and Boland Scheme 25.19), C26-C40 subunit of spirastrellolide 162 (Paterson et al. Scheme 25.20), disparlure 165 (Oehlschlager, Scheme 25.21), exo-brevicomin 168 (Jayaraman, Scheme 25.22). 

Several syntheses of natural products have been achieved with EHs as the key steps to introduce chirality. One of the first was the synthesis of the biologically active enantiomer of disparlure, the sex pheromone of the moth Lymantria dispar, which causes severe damage to trees in some parts of the world [159]. The synthesis was based on the kinetic resolution, mediated by a Pseudomonas strain, of rac-9,10-epoxy-15-methyl hexadecanoic acid, a precursor of the pheromone. The residual epoxide was then chemically converted in a Kolbe reaction into (+)-disparlure in 95% ee (Figure 8.41). 

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