Stereochemical Course of an Enzyme-Catalyzed Allene-Acetylene Isomerization

Article abstract of DOI:10.1021/ja00307a037

An allene-acetylene isomerase (AAI) isolated from hog liver interconverts the N-acetylcysteamine thio ester of 3-decynoic acid (3-decynoyl-NAC) and (+)-2,3-decadienoyl-NAC.It is thus far the only enzyme that has been isolated that produces (or utilizes) an allenic compound and that is not inactivated by that same allene.Although physical and kinetic characteristics of the enzyme have previously been obtained, details of its mechanism of action remain unknown.The stereochemical course of the AAI-catalyzed propalgylic rearrangement has now been determined, by synthesis of 2,3-<2-2H>- and 2,3-<4-2H> decadienoyl-NAC and enzymatic conversion of these substrates to 3-<2-2H₁>decanoyl-NAC.Derivatization of the chirality labeled acetylenes, followed by 2H NMR analysis, has shown that protonation occurs on the si face at C-2 of the allene.X-ray crystallographic analysis of a derivative has revealed that (+)-2,3-decadienoic acid possesses the S configuration.The enzyme-mediated propargylic rearrangement is therefore a suprafacial process, apparently involving a single active-site base.