Stereoselectivity ratios

Stereoselectivity was defined by Rauws as follows Stereoselectivity is the extent to which an enzyme or other macromolecule, or macromolecular structure (antibody or receptor) exhibits affinity towards one molecule of a pair of isomers in comparison with and in contrast to the other isomer. . Lehmann has expressed this in a mathematical form the ratio of activity of the better fitting enantiomer (eutomer greek, eu = good), to that of the less fitting enantiomer (distomer greek, dys = bad) is defined eud-ismic ratio. From this an eudismic affinity quotient can be derived (Table 26.3). 

When the activity of the eutomer Eu is compared to that of the racemic mixture Rac, four possibilities can arise  

The activity ratio is equal to 2 Eu/Rac = 2/1. In this case the activity is only concentrated in the eutomer and the distomer does not contribute significantly to the observed activity. The chiral compound shows stereoselectivity. 

The activity ration is higher than 2 Eu/Rac 2 (e.g. Eu/ Rac = 2/0.3). This means that the distomer represents a competitive antagonist of the eutomer. In the practice such a situation is rather exceptionally encountered (see section V Practical Considerations B. The distomer counteracts the eutomer.  

Distomer (Dis) Enantiomer presenting the lowest affinity (or activity) 

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When using methyllithium instead of methylmagnesium chloride for the alkylation of 12, the product is obtained in good yield (70%) however the dia-stereoselective ratio drops to 5 1 in favour of alcohol 13. 

Banks (151) has reported the decarbalkoxylation (NaCl in wet DMSO at 148-153°C) of the geminal diesters 490 and 493. He found that the reaction of 490 was highly stereoselective yielding the axial isomer 491 in preference to the more stable equatorial isomer 492 (ratio =9 1). On the other hand, the reaction of 493 was non-stereoselective (ratio =1 1 of 494 and 495). 

D. Stereoselectivity ratios ASPECTS to unwanted or toxic products... 

The stereoisomers of some oxotremorine analogs containing two chiral centers and acting as oxotremorine antagonists show in vivo (tremorolytic activity) stereoselectivity ratios as high as 1 to 200. ... 

In the second reaction type, the ene and yne functionalities are found in two different phosphorus substituents. These 1-alkynylphosphonates undergo facile Pd(OAc)2-LiCl-catalyzed cyclization to give oxaphospholanes in good yields (77-89%, Scheme 1.27) but with low stereoselectivity, ratios at the exo double bonds being approximately 60/40. ... 

The stereoselectivity ratios (= antilogs of the difference of respective pA2 values) for 4-F-MePyMcN at Mj, M2 and M3 receptors were very similar [(S)/(R) = 50, 63 and 32, respectively]. In contrast, these ratios of the quaternary analogue, 4-F-MePyMdSr, differed in the three functional pharmacological assays. They were very low at M2 and M3 [(S)/(R) = 2.5 and 4, respectively], but high at Mj receptors [(S)/(R) = 40]. This implies that the stereochemical requirements of the muscarinic receptor subtypes are different for the enantiomers of 4-F-MePyMcN, being most stringent at M receptors. 

COOH group - instead of a OH group - at the central carbon atom displayed a reduced afSnity at all three receptors, but the enantioselecdvity ratios were slightly increased, compared to the parent compound HHD. These results are not in agreement with Pfdffer s rule. Additionally, the eutomer of this carboxylic acid (I-S) displayed higher affinities than its amide 6, and the stereoselectivity ratios were higher for 5 than for 6. 

Shortening of the aminopropyl to an aminoethyl chain in the eutomers of the HHD-deriva-tives (3->8, 4->9, 6- ll) did not change significantly the affinities. In contrast, the stereoselectivity ratios for the enantiomers of these aminopropyl/aminoethyl pairs were changed. It was found, that the stereoselectivity ratios for 3 (aminopropyl series) were higher than those for the related compound in the aminoethyl series (8). Vice versa, the amide of the HHD type (6) exhibited lower eudismic ratios than the amide of the THP type (11). 

The three-point contact model Diastereoisomers Stereoselectivity ratios Pfeiffer s rule... 

Paulsen and HOlck applied a modification of the procedure of Paulsen and coworkers to the synthesis of the fully deprotected L-serine (122) and L-threonine (182) derivatives. Condensation of the 2-azido-2-deoxy chloride 177 with the benzyl ester 146 of L-serine in the presence of silver carbonate, Drierite, molecular sieves 4A, and silver perchlorate in toluene-dichloromethane proceeded with very high stereoselectivity (ratio of a to 19 1) in a yield of 85% a similar condensation with the benzyl ester of L-threonine (183) gave an 81% yield, with similar, high stereoselectivity. This was followed by reduction of the azido to an amino group with sodium borohydride-nickel dichloride, N-acetylation, 0-deacetylation, and deprotection of the amino acid residues, to give 122 and 182, respectively. 

CycUzation of 4-bromobutyl-2electrochemical cleavage of the alkyl-cobalt bond in microemulsions and in DMF. Microemulsions gave a stereoselective ratio of 93 7 trans. cis, but poor stereoselectivity was obtained in homogeneous DMF. Preferential formation of thermodynamically favored trans-l-decalone involved equilibration of isomers via keto-enol tautomerism catalyzed by hydroxide ions formed by the coelectrolysis of water. 

Comparison of the recorded and simulated NMR spectra and the assumption that polyester chain growth is accompanied by exchange of chiral macromolecules on alien active centers indicated that the resulting macromolecules were composed of stereoblocks with 11 repeating units derived from LA monomer of a given kind (toluene, 70 °C). Enantiomerically pure (R)- or (S)-SB02A1-0R initiators have been shown to polymerize preferentially one of the enantiomers of rac-LA, that is, (R,R)- or (S,S)-LA, respec-tively. This enantiospecific preference was indicated by the stereoselectivity ratio fep(R/RR)/fep(R/SS) (or fep(S/SS)/fep (S/RR)) equal to 28, what corresponds to Pm = 0.96 (i.e., probability of isotactic enchainment formation, equal to m diad content in the resulting polymer). 

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