6-Acetoxy-5-hexadecanolides

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. 

This one-pot, three-component reaction has been successfully applied to the total synthesis of (5R,6S)-6-acetoxy-5-hexadecanolide 131 (Scheme 9.23). 

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. 

Kotsuki, H. Kadota, I. Ochi, M. A novel C-C bond-forming reaction of triflates with Cu(I)-catalyzed Grignard reagents. A new concise and enantiospecific synthesis of (+)-e o-brevi-comin, (5 R,6 S) - (-) -6-acetoxy-5 -hexadecanolide, and L-factor. J. Org. Chem. 1990, 55, 4417-4422. 

Compound 33, was allowed to react with BrMg (Ct ) and the syn and anti diastereoisomers so obtained were separated to ultimately yield, (5S,6R) 6-acetoxy-5-hexadecanolide 42 and the... 

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... 

We were eager to exploit this methodology in the total synthesis of a lactone-containing natural product. The target chosen was 6-acetoxy-5-hexadecanolide (7 and 8) (Fig. 1.7), a major component of mosquito oviposition... 

The asymmetric synthesis of both enantiomers of 6-acetoxy-5-hexadecanolide were successfully carried out [24]. This was achieved via initial deprotection of the 1,3-dioxane moiety of compound 9 and subsequent cycUsation, catalysed by ZrCLt, to form 6-methoxytetrahydropyran (10) followed by oxidation to form the natural product 7 (Scheme 1.3). 

Scheme 1.3 Deprotection/cyclisation sequence to 6-acetoxy-5-hexadecanolide...

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). 

Park Y, Tae J (2010) Facile Symthesis of (-)-6-Acetoxy-5-hexadecanolide by Organocatalytic a-Oxygenation-Allylation-RCM Strategy. Synthesis 3627... 

R,6S)-6-Acetoxy-5-hexadecanolide is a pheromone that attracts certain disease-carrying mosquitoes to sites... 

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