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Carboxylic acids are common moieties in medicines. They can be converted to phthalidyl esters as prodrugs. Unfortunately, phthalidyl esters are now mostly prepared in racemic forms. This is not desirable because the two enantiomers of phthalidyl esters likely have different pharmacological effects. Here we address the synthetic challenges in enantioselective modification of carboxylic acids via asymmetric acetalizations. The key reaction step involves asymmetric addition of a carboxylic acid to the catalyst-bound intermediate. This addition step enantioselectively constructs a chiral acetal unit that lead to optically enriched phthalidyl esters. A broad range of carboxylic acids react effectively under mild and transition metal-free conditions. Preliminary bioactivity studies show that the two enantiomers of chlorambucil phthalidyl esters exhibit different anti-cancer activities to inhibit the growth of Hela cells. Our catalytic strategy of asymmetric acetalizations of carboxylic acids shall benefit future development of chiral phthalidyl ester prodrugs and related molecules.

Multisubstituted arenes such as indanes with attached all-carbon quaternary centers are unique scaffolds in synthetic functional molecules and sophisticated natural products.Akey challenge in preparing such molecules lies in the enantioselective installation of the quaternary carbon centers.C onventional methods in this direction include asymmetric substitution reactions and substrate-controlled cyclization reactions.T hese reactions lead to poor stereoselectivities and/or require long and tedious synthetic steps.Disclosed here is ao ne-step organic catalytic strategy for enantioselective access to this class of molecules.T he reaction involves an Nheterocyclic carbene catalyzedp rocess for direct benzene construction, indane formation, remote-carbon desymmetrization, and excellent chirality control. This approach will enable the concise synthesis of arene-containing molecules,i ncluding those with complex structures and challenging chiral centers.

Folic acid-conjugated glucose and dextran coated SPIO nanoparticles were used for the diagnosis and treatment response of rheumatoid arthritis.

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