Stereoisomers discovery

The importance of the three stereogenic centers became evident as two of the stereoisomers [(2S,3S,7S) and (2S,3R,7R)] were recognized early as sex pheromones and that other enantiomers and diastereoisomers were often found to be inhibitory to the attractive response. Recently, the sawfly pheromone field has undergone a major advance with the recognition that several sawfly species synthesize and utilize sex pheromones of different structural types than the 3,7-dimethylpentadecan-2-ols. Shorter and longer chain lengths (undecan-2-ols 2 and tridecan-2-ols 3) and an additional methyl group in position 9 or 11 (4 and 5) characterize these new pheromone discoveries (Fig. 1). With an ad-... 

The Diels-Alder reaction is a powerful synthetic process for constructing complex molecules. The reaction has been extensively studied and refined since its discovery in 1928.1 The most attractive feature of the Diels-Alder reaction is its simultaneous, regioselective construction of two bonds, resulting in the creation of up to four chiral centers with largely predictable relative stereochemistry at the bond formation sites. Theoretically, there are a total of 24 = 16 stereoisomers when atoms marked with an asterisk are all chiral centers (Scheme 5-1) therefore, the complete control of the reaction process to obtain enantiomeri-cally pure products has been the object of active research in many laboratories. 

Fink, T. and Reymond, J.-L. (2007) Virtual exploration of the chemical universe up to 11 atoms of C, N, O, F assembly of 26.4 million structures (110.9 million stereoisomers) and analysis for new ring systems, stereochemistry, physicochemical properties, compound classes, and drug discovery. Journal of Chemical Information and Computer Sciences, 47, 342-353. 

In order to carry out this reaction by a one-pot procedure, we examined the same complexation reaction in the presence ofaketene acetal, which led us to the discovery of the novel reaction pathways described below [32]. Thus, treatment of o-ethynylphenyl ketone 104 with a catalytic amount of W(CO)5(thf) in the presence qf4equiv of 1,1-diethoxyethylene at rt gave a novel polycyclic compound 120 in good yield as a single stereoisomer. Both vinyl ethers and ketene acetals can be employed as the electron-... 

Having identified the (+)-stereoisomer as the biologically active isomer, several independent enantioselective syntheses of this stereoisomer were developed. The initial synthesis developed in discovery chemistry employed the diastereoselective aldol condensation pioneered by Braun as the key component. Thus, treatment of aldehyde 13 from the racemic synthesis with the magnesium enolate of (5)-(+)-2-acetoxy-l,l,2-triphenylethanol at -70 °C, afforded 17 in 60% yield as a 97 3 mixture of the / ,5 5,5-diastereomers by HPLC (Scheme 3). Ester exchange employing sodium methoxide provided the methyl ester in quantitative yield. Reaction of this ester with three equivalents of lithio-f-butylacetate at -40 °C afforded the nearly enantiomerically pure r-butyl ester analog of racemic 14 in 75% yield. 

All of the threonine stereoisomers 19-22 are chiral substances that is, they are not identical with their mirror images. However, it is important to recognize that not all diastereomers are chiral. To illustrate this point, we return to the tartaric acids mentioned previously in connection with Pasteur s discoveries (Section 5-1C). 

Synthetic pyrethroids are a group of ester compounds having excellent insecticidal activities. After the discovery of allethrin (1), a variety of useful synthetic pyrethroids have been produced mainly by structural modification of an alcohol having an asymmetric center. The insecticidal activities greatly depend upon the stereoisomers. Therefore, much effort has been expended to develop technologies for obtaining optically active isomers. However, contrary to the case of chrysanthemic acid, chemical methods of optical resolution were not very effective for these alcohols. 

Lets look at one more exampte of a compound with two chirality centers tartaric acid. We re already acquainted with tartaric acid because of its role in Pasteur s discovery of optical activity, and wv can now draw the four stereoisomers ... 

In the drug discovery process only the naturally available stereoisomer of a natural product is generally tested and promoted to chnical studies. The structures of many natural products are rather complex in comparison to synthetic drugs. A synthetic approach to obtain both enantiomers or defined diastereoisomers is often not feasible and beyond fhe scope of medicinal chemistry, despite the tremendous progress in the field of stereoselective synfhesis during fhe last 20 years. 

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