Pheromone enantioselective synthesis

Aspects of pheromone synthesis have been reviewed [46h, 46i, 47, 145,146], including the enantioselective synthesis of pheromones. Enantioselective synthesis of a chiral and non-racemic pheromone can be executed by one of the following three methods [46h] ... 

The optically active propargylic and allylic alcohols thus obtained are important synthetic intermediates in the enantioselective synthesis of insect pheromones, prostaglandins, prostacyclins, and many other bioactive compounds (Scheme 6-26).53... 

Sn2 Reactions with epoxides and aziridines are also synthetically useful. An example of epoxide cleavage with an organocopper reagent with sp carbon moieties is the enantioselective synthesis of (3S, 4S)-4-methyl-3-heptanol (53), an elm bark beetle (Scolytus multistriatus) pheromone [42]. The chiral epoxy oxazolidine 51 [43], prepared from (R)-phenylglycinol, reacted with a propylmagnesium bromide-derived cuprate at —70 °C to afford the oxazolidine 52 in 74% yield (Scheme 9.12). Compound 52 was converted into the target molecular 53 by conventional procedures. 

Moreira, J.A. and Correa, A.G. (2003). Enantioselective synthesis of three stereoisomers of 5,9-dimethylpentadecane, sex pheromone component of Leucoptera coffeella, from (-)-isopulegol. Tetrahedron Asymm., 14, 3787-3795. 

Becker, D., Cyjon, R., Cosse, A., Moore, I., Kimmel, T. and Wysoki, M. (1990). Identification and enantioselective synthesis of (Z,Z),6,9-cis-3S,4R-epoxynonadecadiene, the major sex pheromone component of Boarmia selenaria. Tetrahedron Lett., 31,4923 4926. 

Periplanone C. McMurry has reported an enantioselective synthesis of (-)-periplanone C, a sesquiteipene that serves as a sex pheromone for cockroaches, through a route involving a pinacol cyclization of a 1,10-keto aldehyde (Eq. 3.7) [24]. MM2 calculations based on a model for predicting the stereoselection of titanium-mediated pinacol coupling reactions were in qualitative, but not quantitative, agreement with the experimental results. 

There are three methods available for the enantioselective synthesis of pheromones (1) derivation from enantiopure natural products, (2) enantiomer separation (optical resolution), and (3) chemical or biochemical asymmetric synthesis. Practitioners of enantioselective synthesis must be familiar with the analytical methods for the determination of enantiomeric purity of an optically active compound. These basic methods will be explained briefly in this section, and discussed in depth through examples in the later sections of this chapter. 

Accordingly, enantioselective synthesis of a pheromone with known absolute configuration was the only realistic method to determine its absolute configuration and supply a sample in an amount sufficient for its biological evaluation. Of course, it was also possible to compare the chiroptical properties of the synthetic pheromone with those of the naturally occurring ones. These biological and physical comparisons of the natural pheromone with those of its synthetic enantiomers were the only way to determine the absolute configuration of a pheromone. 

The Anal task was to carry out an enantioselective synthesis of the natural pheromone (2Z,6R,l S,5 S)-75. Figure 4.13 summarizes our synthesis of the pheromone.28 Hodgson s intramolecular cyclopropanation procedure (D->-E) could be employed successfully.29 The synthetic pheromone amounted to about 400 mg, which was enough to carry out further biological studies. The acetate of (2Z,6R,l,.S ,5,.S )-75 was shown to be identical with the acetate isolated in 1982 from an African plant Haplocarpha scaposa by Bohlmann and... 

Enders has used these asymmetric Michael additions as the key steps in the enantioselective synthesis of various esters and alcohols (69-73) which are chiral volatile ant pheromones. In these syntheses, asymmetric Michael additions of the lithio salt of the SAMP hydrazone of propanal to methyl 2-but-enoate and methyl 2-pentenoate were used to establish the chiral centers. Subsequent hydrolysis and reduction of the aldehyde or carboxylic acid ester by conventional procedures afforded the pheromones. ... 

The same methodology is applied in the enantioselective synthesis of iodo ether 23, a key precursor of ( + )-faranal (24) (a trail pheromone of the Pharaoh s ant)969. 

The designation chiral pool was introduced to denote an available source of enantiomerically pure natural products. These include the (5)-amino acids, as well as (iS)-lactic acid, (5)-malic acid, (RJl)-tartaric acid and / -D-glucose. How the knowledge of their chirality can be utilized for asymmetric syntheses is demonstrated by an example of the chiral auxiliaries S) and (i )-l-amino-2-(methoxymethyl)pyrrolidine developed by Enders and abbreviated as SAMP (2) and RAMP [61]. They are synthesized from (5)- or (R)-proline in several steps [62]. The enantioselective synthesis of the insect pheromone (5)-4-methylheptan-3-one 8 by alkylation of pentan-3-one 1 serves as an example for the use of these chiral auxiliaries ... 

Brassinosteroids, Brevicomin, Chirality, Enantioselective Synthesis, Gibberellins, Glycinoeclepin A, Juvenile Hormones, Minamata Disease, Pheromones, Phytoalexins, Strigolactones... 

In 1969, Glenn W. Kinzer [197] isolated frontalin, an important component of the aggregation pheromone of these beetle species. [198] In 1998, Mori published an enantioselective synthesis of this pheromone. [199] Key steps are the enantioselective reduction of the jS-keto-ester, the diastereoselective methyla-tion and the Baeyer-VUliger oxidation. The methylation proceeds under chelation control, and gives the desired methylation product with excellent diastereo-selectivity. 

Using catalytic amounts of the morphoUne salt of a chiral phosphoric acid such as compound 241 and Hantzsch ester 242 as the hydride source. List et al. were able to achieve highly selective reductions of a broad variety of a,p-unsaturated carbonyl compounds like famesal (243) as demonstrated in the enantioselective synthesis of the bee pheromone (/ )-244 (210) (Scheme 56). Notably, this method was found to be superior when compared to the use of chiral amine-based catalysts with respect to enantioselectivity in several examples employing stericaUy unhindered aliphatic aldehydes (209). 

The enantioselective synthesis of the insect pheromone (S)-4-methylheptan-3-one (21) by alkylation of pentan-3-one (18) may serve as an example for the use of these chiral auxiliaries [239] ... 

SCHEME 28.5. Enantioselective synthesis of the key building block o-DPPB-ester 11 in the total synthesis of the pheromone vittatalactone (o-DPPB ortho-diphenylphosphanylbenzoate). 

Schotten, X, Boland, W, and Jaenicke, L. (1986) Enantioselective synthesis of dictyopterene C 6R-(—)-butyl-2,5-cycloheptadiene, the pheromone of several dictyotales (Phaeophyceae), Tetrahedron Lett., 27, 2349-2352. 

Solladie, G., Somny, F., and Colobert, F. (1997) Enantioselective synthesis of haminol-1, an alarm pheromone of a mediterranean mollusc. Tetrahedron Asymmetry, 8, 801-810. 

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