The convulsant and anesthetic properties of cis-trans isomers of 1,2-dichlorohexafluorocyclobutane and 1,2-dichloroethylene.

UNLABELLED: The differences in potencies of optical isomers of anesthetics support the hypothesis that anesthetics act by specific receptor interactions. Diastereoisomerism and geometrical isomerism offer further tests of this hypothesis but have not been explored. They are the subject of this report. We quantified the nonimmobilizing and convulsant properties of the cis and trans diastereomers of the nonimmobilizer 2N (1,2-dichlorohexafluorocyclobutane). Although the lipophilicity of the diastereomers predicts complete anesthesia at the partial pressures applied, neither diastereomer had anesthetic activity alone, and the cis form may have a small (10%) capacity to antagonize anesthesia, as defined by additive effects on the MAC (the minimum alveolar concentration required to suppress movement to a noxious stimulus in 50% of rats) of desflurane. Both diastereomers produced convulsions, the cis form being nearly twice as potent as the trans form: convulsant 50% effective dose (mean +/- SD) was 0.039 +/- 0.009 atmospheres (atm) for the purified cis and 0.064 +/- 0.009 atm for the purified trans isomer. The MAC value for cis-1,2-dichloroethylene equaled 0.0071 +/- 0.0006 atm, and MAC for trans-1,2-dichloroethylene equaled 0.0183 +/- 0.0031 atm. In qualitative accord with the Meyer-Overton hypothesis, the greater cis potency was associated with a greater lipophilicity. However, the product of MAC x solubility differed between the cis and trans isomers by 40%-50%. We conclude that neither the cis nor trans isomers of 2N have anesthetic properties, but isomerism does influence 2N's convulsant properties and the anesthetic properties of dichloroethylene. These isomeric effects may be as useful in defining receptor-anesthetic interactions as those found with optical isomers. IMPLICATIONS: Cis-trans isomerism can influence the convulsant properties of the nonimmobilizer 2N (1,2-dichlorohexafluorocyclobutane) and the anesthetic properties of dichloroethylene. Such isomeric effects may be as useful as those found with optical isomers in defining receptor-anesthetic interactions.

Microbial Baeyer-Villiger reaction of bicyclo[3.2.0]heptan-6-ones--a novel approach to sarkomycin A.

Racemic (1 alpha, 2 alpha, 5 alpha)- and (1 beta, 2 alpha, 5 beta)-2- bromobicyclo[3.2.0]heptan-6-one (rac-7, rac-10, respectively), (1 alpha, 2 alpha, 5 beta)- and (1 beta, 2 alpha, 5 beta)-2- benzyloxybicyclo[3.2.0]heptan-6-one (rac-15, rac-13, respectively), (1 beta, 2 alpha, 5 beta)-2-hydroxybicyclo[3.2.0]heptan-6-one (rac-17) and cis-bicyclo[3.2.0]hept-2-en-7-one (rac-18) were subjected to a microbial Baeyer-Villiger reaction by Acinetobacter calcoaceticus NCIB 9871. In each case both regioisomeric lactones were formed (67-93% yield) having always the opposite configuration (20 to > 99 % e.e.). Both the ratio of the regioisomers and the enantiomeric excess proved to be dependent on the type of substitution. Analogously cis-bicyclo[3.2.0]heptan-2,6-dione (rac-1) gave besides other products cyclosarkomycin (1b) (7 % yield, 97 % e.e.). Compound 1b was also obtained from the Baeyer-Villiger product of rac-17 by Swern oxidation (total yield starting from rac-17 9 %, > 98 % e.e.).

Strategies for the chemoenzymatic preparation of optically active 1-alkyn-3-ols.

A series of (R)- and (S)-1-alkyn-3-ols, chiral building units for the synthesis of leukotrienes and pheromones, were prepared via enantioselective hydrolysis of their racemic esters. While the majority of biocatalysts employed (lipases, fermenting or freeze-dried microorganisms) failed in discriminating between enantiomers, lyophilized cells of baker's yeast (Saccharomyces cerevisiae Hansen) gave (S)-1-alkyn-3-ols and their corresponding (R)-esters with greater than 90% e.e.