Formal Total Synthesis of RK-397 via an Asymmetric Hydration and Iterative Allylation Strategy

A formal total synthesis of the oxopentaene macrolide antibiotic RK-397 has been achieved. Nine stereocenters were established by a combination of allylation and our asymmetric hydration reactions and a 1,5-anti-selective aldol reaction. The synthesis proceeded in 19 steps from simple achiral conjugated dienoates

De Novo Synthesis of 2-Substituted <i>syn</i>-1,3-Diols via an Iterative Asymmetric Hydration Strategy

The enantioselective syntheses of several protected 4-substituted syn-3,5-dihydroxy carboxylic esters have been achieved from the corresponding achiral (E,E)- or (E,Z)-1,3-dienoates. The route relies upon an enantio- and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to form γ-substituted δ-hydroxy-1-enoates. The resulting δ-hydroxy-1-enoates are subsequently converted into benzylidene-protected 4-substituted syn-3,5-dihydroxy carboxylic esters in one step. The benzylidene-protected 3,5-dihydroxy carboxylic esters are produced in good overall yields (20−54%) and high enantiomeric excess (73−97% ee)

De Novo Formal Synthesis of (−)-Virginiamycin M₂ via the Asymmetric Hydration of Dienoates

A de novo approach to the formal total synthesis of the macrolide natural product (−)-virginiamycin M2 has been achieved via a convergent approach. The absolute and relative stereochemistry of the nonpeptide portion of (−)-virginiamycin M2 was introduced by two Sharpless asymmetric dihydroxylation reactions