title: Epimerization of glycal derivatives by a cyclopentadienylruthenium catalyst: application to metalloenzymatic DYKAT.
abstract: Epimerization of a non-anomeric stereogenic center in carbohydrates is an important transformation in the synthesis of natural products. In this study an epimerization procedure of the allylic alcohols of glycals by cyclopentadienylruthenium catalyst 1 is presented. The epimerization of 4,6-O-benzylidene-D-glucal 4 in toluene is rapid, and an equlibrium with its D-allal epimer 5 is established within 5 min at room temperature. Exchange rates for allal and glucal formation were determined by 1D (1) H EXSY NMR experiments to be 0.055 s(-1) and 0.075 s(-1) , respectively. For 4-O-benzyl-L-rhamnal 8 the epimerization was less rapid and four days of epimerization was required to achieve equilibration of the epimers at room temperature. The epimerization methodology was subsequently combined with acylating enzymes in a dynamic kinetic asymmetric transformation (DYKAT), giving stereoselective acylation to the desired stereoisomers 12, 13, and 15. The net effect of this process is an inversion of a stereogenic center on the glycal, and yields ranging from 71 % to 83 % of the epimer were obtained.
authors.affiliation: Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 106 91 Stockholm (Sweden).
authors.forename: Richard
authors.initials: R
authors.lastname: Lihammar
authors.forename: Jerk
authors.initials: J
authors.lastname: Rönnols
authors.forename: Göran
authors.initials: G
authors.lastname: Widmalm
authors.forename: Jan-E
authors.initials: JE
authors.lastname: Bäckvall
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D002384:Catalysis; D056831:Coordination Complexes / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D020005:Propanols / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D002241:Carbohydrates; D056831:Coordination Complexes; D020005:Propanols; C006463:allyl alcohol; D012428:Ruthenium
keywords: NMR spectroscopy; carbohydrates; dynamic kinetic asymmetric transformation; enzyme catalysis; inversion