1. Influence of the methyl group in isoprene epoxides on reactivity compared to butadiene epoxides: Biological significance
Bernard T Golding, et al. Chem Biol Interact. 2022 Jul 1;361:109949. doi: 10.1016/j.cbi.2022.109949. Epub 2022 Apr 29.
Reactions of the epoxides of 1,3-butadiene and isoprene (2-methyl-1,3-butadiene) with oxygen, nitrogen and sulfur nucleophiles have been compared to enable a better molecular understanding of the relative human toxicities of these epoxides. Hydrolysis of rac.-ethenyloxirane in (18O)water gave 77% (2-18O)but-3-ene-1,2-diol and 23% (1-18O)but-3-ene-1,2-diol. The R:S ratio for but-3-ene-1,2-diol from hydrolysis of (S)-ethenyloxirane was 75:25. Hence, hydrolysis of ethenyloxirane occurs by competing SN2 attack at C-2 and C-3 in 3:1 ratio, with no SN1 component. Hydrolysis of rac.-2-ethenyl-2-methyloxirane gave 2-hydroxy-2-methylbut-3-en-1-ol (73%) and 27% of a 2:1 mixture of the E- and Z-isomers of 4-hydroxy-2-methylbut-2-en-1-ol. In (18O)water (2-18O)2-hydroxy-2-methylbut-3-en-1-ol was obtained. Formation of these products occurs via SN1 ionisation to resonance-stabilised allylic cations which are captured by water. Reaction of rac.-ethenyloxirane with l-valine methyl ester gave diastereoisomeric adducts from SN2 attack of the valine amino at both C-2 (substituted position) and C-3 of the oxirane. The corresponding reaction of rac.-2-methyl-2-ethenyloxirane gave diastereoisomeric adducts, (R, S)- and (S, S)-N-(2-hydroxy-2-methyl-3-buten-1-yl)-l-valine methyl ester, from SN2 attack of the valine amino solely at C-3. Reactions of rac.-2-ethenyl-2-methyloxirane with cysteine derivatives occurred at C-2 in neutral polar media (SN1 reaction) or at C-3 in basic media (SN2), whereas for ethenyloxirane products arose from attack at both C-2 and C-3. Reaction of meso-butadiene diepoxide (meso-2,2'-bioxirane) with l-valine methyl ester gave mainly 2:1 adducts, dimethyl 2,2'-(((2R,3S)-2,3-dihydroxybutane-1,4-diyl)bis(azanediyl))-(2S,2'S)-bis(3-methyl-butanoates), whereas 2-methyl-2,2'-bioxirane gave a mixture of 1:1 [methyl 2-(3,4-dihydroxy-3-methylpyrrolidin-1-yl)-3-methylbutanoates] and 2:1 adducts. Meso-2,2'-bioxirane reacted with N-acetylcysteine methyl ester in methanol to afford meso-thiolane-3,4-diol, by elimination of N-acetyldehydroalanine methyl ester from a precursor cyclic adduct. Similarly, 2-methyl-2,2'-bioxirane gave solely 3-methylthiolane-3,4-diols. Thus, the methyl group of isoprene has a subtle effect on the reactivity of its epoxides relative to those of butadiene and therefore, in the context of their toxicology, could abrogate crosslinking of nitrogen functions in biomolecules related to mutagenicity and carcinogenicity.
2. (1R*,2R*,3S*,4R*)-Diethyl 4-hy-droxy-4-methyl-2-(4-methyl-phen-yl)-6-oxo-cyclo-hexane-1,3-di-carboxyl-ate
Arif I Ismiev, Narmina A Gadirova, Kushvar E Hajiyeva, Rizvan K Askerov, Konstantin A Potekhin Acta Crystallogr Sect E Struct Rep Online. 2013 Apr 13;69(Pt 5):o734. doi: 10.1107/S1600536813009872. Print 2013 May 1.
The title compound, C20H26O6, is chiral and crystallizes as a racemate: the relative configuration of the stereogenic centres is 1R*,2R*,3S*,4R*. The cyclo-hexane ring has a chair conformation. The ethyl fragment of the eth-oxy-carbonyl group in the 3-position is disordered over two sets of sites in a 0.650 (6):0.350 (6) ratio. The hy-droxy group acts as a bifurcated hydrogen-bond donor, forming both intra- and inter-molecular hydrogen bonds with ester carbonyl O atoms. The inter-molecular hydrogen bonds form inversion dimers in the crystal.
