Synthesis of saccharinic acid derivatives

An Efficient and Diastereoselective Synthesis of PSI-6130: A Clinically Efficacious Inhibitor of HCV NS5B Polymerase

“…We envisioned introduction of the C-2 fluorine functionality via stereoselective displacement of an activated hydroxyl group on an acyclic intermediate ( 5 ) to form 4 . Aparicio, Cubero, and Olea described the synthesis of ethyl 4,5- O -isopropylidine-2- C -methyl- dl -arabinoate via osmium tetraoxide mediated dihydroxylation of a pentenoate precursor that met our needs. In their earlier synthesis of the pentenoate, they used a Knoevenagel−Doebner condensation on isopropylidene protected d -glyceraldehyde.…”

“…Osmium tetraoxide can approach the double bond of the pentenoate from either face and therefore create two diastereomers for each of the geometric isomers. Cubero observed that treating purified geometric dl isomers with catalytic osmium tetraoxide and potassium chlorate resulted in roughly equal facial selectivity for the Z -isomer and 2:1 for desired arabinoate from the E -isomer. In our early work, we used Sharpless AD-mix-β catalyst to direct the attack to the desired face and create the correct stereochemistry in 91% yield after chromatography.…”

Catalytic Asymmetric Synthesis of anti-1,2-Diols

“…Similarly, the reaction with the protected glyceraldehyde gave known d -tagatose derivative 6 ([α] D = + 69°, lit . [α] D = + 71°) together with the syn byproduct 1-deoxy-5,6- O -isopropylidene- d - fructose having the opposite configuration at the β-position . These hexoses are readily converted into the natural sugars 1-deoxy- d -tagatose and 1-deoxy- d -fructose. , Absolute configurations of diols 2 - 5 have been assigned based on the crystal structure of diol 1 (Figure ) and on the absolute configuration of the known products of the reaction with the enantiomerically pure glyceraldehyde-substrate (entry 6, Table ).…”

“…[α] D = + 71°) together with the syn byproduct 1-deoxy-5,6- O -isopropylidene- d - fructose having the opposite configuration at the β-position . These hexoses are readily converted into the natural sugars 1-deoxy- d -tagatose and 1-deoxy- d -fructose. , Absolute configurations of diols 2 - 5 have been assigned based on the crystal structure of diol 1 (Figure ) and on the absolute configuration of the known products of the reaction with the enantiomerically pure glyceraldehyde-substrate (entry 6, Table ). The enantiofacial selectivity ( re ) of the aldehyde in these reactions is identical to that obtained using acetone as the aldol donor.…”