Joseph M. Langenhan

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The use of a simple fluorescent nucleoside analogue in detection of point mutations by hybridization in solution is described. Pyrene is placed at 3' and 5' ends of a pair of oligodeoxynucleotide probes via a phosphoramidite derivative of deoxyribose with this fluorophore attached at the 1' position, replacing a DNA base. Adjacent binding of dual probes(More)
We report the synthesis of syn-alpha,beta-dialkyl beta-amino acid derivatives suitably protected for solid-phase synthesis that give rise to residues containing positively charged lysine-like side chains. These amino acids, as well as syn-alpha,beta-dialkyl beta-amino acids that contain diverse hydrophobic side chains, are prepared in good de and ee. The(More)
Glycosylated natural products are reliable platforms for the development of many front-line drugs, yet our understanding of the relationship between attached sugars and biological activity is limited by the availability of convenient glycosylation methods. When a universal chemical glycosylation method that employs reducing sugars and requires no protection(More)
In an effort to explore the contribution of the sugar constituents of pharmaceutically relevant glycosylated natural products, chemists have developed glycosylation methods for the generation of 'glycorandomized' libraries. Each member of these libraries is uniquely differentiated by an attached carbohydrate. Recently, two complementary glycorandomization(More)
In an effort to explore the contribution of the sugar constituents of pharmaceutically relevant glycosylated natural products, chemists have developed glycosylation methods that are amenable to the generation of libraries of analogues with a broad array of glycosidic attachments. Recently, two complementary glycorandomization strategies have been described,(More)
Digitoxin is a cardiac glycoside currently being investigated for potential use in oncology. While a number of structure-activity relationship studies have been conducted, an investigation of anticancer activity as a function of oligosaccharide chain length has not yet been performed. We generated mono-, di-, and tri-O-digitoxoside derivatives of digitoxin(More)
The asymmetric synthesis of the potent immunosuppressive agent (-)-pateamine A isolated from the marine sponge Mycale sp. is described. A key strategy employed in the synthesis was a â-lactam-based macrocyclization to form the 19-membered dilactone macrolide. The synthesis confirms the relative and absolute stereochemistry as 3R,5S,10S,24S and sets the(More)
A chemoselective reaction between oxyamines and unprotected, unactivated reducing sugars was used to construct for the first time a panel of linkage-diversified neoglycosides. This panel of digitoxin analogs included potent and selective tumor cytotoxins; cytotoxicity was dependent on the structure of the glycosidic linkage. These results validate linkage(More)