Mosquito oviposition pheromone, synthesi

Synthesis of (—)-(5i , 6S)-6-acetoxyhexadecanolide, a mosquito oviposition pheromone of Culexpipiens fatigans, was also prepared by asymmetric synthesis. 

Couladouros, E. A., Mihou, A. P. A general synthetic route towards y- and 5-lactones Total asymmetric synthesis of (-)-muricatacin and the mosquito oviposition pheromone (5R,6S)-6-acetoxy-hexadecanolide. Tetrahedron Lett. 1999, 40,4861-4862. 

As depicted in Scheme 7, the synthesis of the mosquito oviposition pheromone (-)-6-acetoxy-5-hexadecanolide (28) via an intermolecular aldol reaction represents a powerful demonstration of the high potential of asymmetric enamine catalysis (45, 46). It is noteworthy that a methodologically different successful organocatalytic approach towards 28, based on an asymmetric a-oxygenation, was reported recently (727). Reaction of aldehyde 136 with dibenzoyl peroxide (BzOOBz) and hydroqui-none (HQ) (722) in the presence of the TMS-protected prolinol catalyst (S)-138 followed by a direct allyation gave the benzoyl-protected 139 in moderate yield and good selectivity. Intermediate 139 could then be further transformed to give (—)-(57 ,65)-6-acetoxy-5-hexadecanolide (28) (Scheme 33). 

This hetero-Diels-Alder step marks the first catalytic enantioselective preparation of a C-chiral aUylboronate (i.e., 97). Key to this process is that the possible self-aUylbo-ration between 95 and 97 is avoided by the higher temperature required in the allylb-oration step. An application of this three-component reaction to the synthesis of a mosquito oviposition pheromone was also described. 

A review of syntheses of the Prelog-Djerassi lactonic acid includes carbohydrate-based routes,27 and there have been two further reports of syntheses of the P-hydroxy-5-lactone unit (38) of mevinic acid and its congeners.28, 29 jn a synthesis of the mosquito oviposition pheromone (39), the chiral centres were derived from those of 2,3-0-ethylidene-D-erythrose, with this chiron being extended by Wittig reactions, in a similar manner to the use of 2-deoxy-D-ribose in an earlier approach to the same target (S.-K. Kang and I.-H. Cho, Tetrahedron Lett., 1989, 30, 743). 

Scheme 41 summarizes Couladouros s synthesis of the oviposition attractant pheromone of the Southern house mosquito (Culexpipiensfatigans)y (5R,6S)-6-acetoxy-5-hexadecanolide (28) [66]. The key-steps are (i) -selective Schlosser olefination (A B), asymmetric dihydroxylation (B C), and lactonization of carbonate C to the desired 6-lactone with inversion at C-5. 

Based on the previous work of this group on the three-component aza[4+2]/ allylboration strategy to construct polysubstituted piperidines [62], Gao and Hall developed a catalytic enantioselective version [63] of the corresponding oxygeneous process to construct a-hydroxyalkylated pyrans from 3-boronoacrolein [64], This recent variant of a Vaultier-Lallemand one-pot three-component reaction (see Scheme 12.14) was successfully applied to a concise total synthesis of (5R,6S)-6-acetoxy-5-hexadecanolide 128 (Scheme 12.20), the oviposition attractant pheromone of the female Culex mosquito [65] capable of transmitting the West Nile virus. 

The enantiospecific synthesis of ( + )-ef7r/zro-(5 S, 6i )-6-acetoxy-5-hexadecanolide (475), an optically active form of the major component of an oviposition attractant pheromone of the mosquito Culexpipiens fatigans, exploits the 6,8-dioxabicyclo[3.2.1]octane system to provide... 

A methodologically similar approach was successfully utilized independently for the synthesis of the oviposition attractant pheromone of the female Culex mosquito (—)-(5/ ,6S )-6-acetoxyhexadecanolide (28), by Kotsuki et al. 45) and Li et al. 46). While the Li group carried out a direct aldol reaction between undecanal (23) and cyclopentanone (24) to obtain the desired isomer 25 in excellent enantio- and diastereoselectivity, the Kotsuki group introduced the stereogenic centers by a reaction between 24 and the dithiane 26 under solvent-free conditions (Scheme 7). 

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