Dinah Dutta

Polymer-bound triphenylphosphine as traceless reagent for mitsunobu reactions in combinatorial chemistry: Synthesis of aryl ethers from phenols and alcohols

Abstract The synthesis of aryl ethers from phenols and alcohols using polymer-bound triphenylphosphine and diethyl azodicar☐ylate (DEAD) is described. The polymer-bound triphenylphosphines are easily removed by filtration from the reaction products. This method is operationally simple and provides the products with high purity and in good yields.

Synthesis and Evaluation of Eight- and Four-Membered Iminosugar Analogues as Inhibitors of Testicular Ceramide-Specific Glucosyltransferase, Testicular β-Glucosidase 2, and Other Glycosidases

Eight- and four-membered analogues of N-butyldeoxynojirimycin (NB-DNJ), a reversible male contraceptive in mice, were prepared and tested. A chiral pool approach was used for the synthesis of the target compounds. Key steps for the synthesis of the eight-membered analogues involve ring-closing metathesis and Sharpless asymmetric dihydroxylation and for the four-membered analogues Sharpless epoxidation, epoxide ring-opening (azide), and Mitsunobu reaction to form the four-membered ring. (3S,4R,5S,6R,7R)-1-Nonylazocane-3,4,5,6,7-pentaol (6) was moderately active against rat-derived ceramide-specific glucosyltransferase, and four of the other eight-membered analogues were weakly active against rat-derived β-glucosidase 2. Among the four-membered analogues, ((2R,3S,4S)-3-hydroxy-1-nonylazetidine-2,4-diyl)dimethanol (25) displayed selective inhibitory activity against mouse-derived ceramide-specific glucosyltransferase and was about half as potent as NB-DNJ against the rat-derived enzyme. ((2S,4S)-3-Hydroxy-1-nonylazetidine-2,4-diyl)dimethanol (27) was found to be a selective inhibitor of β-glucosidase 2, with potency similar to NB-DNJ. Additional glycosidase assays were performed to identify potential other therapeutic applications. The eight-membered iminosugars exhibited specificity for almond-derived β-glucosidase, and the 1-nonylazetidine 25 inhibited α-glucosidase (Saccharomyces cerevisiae) with an IC(50) of 600 nM and β-glucosidase (almond) with an IC(50) of 20 μM. Only N-nonyl derivatives were active, emphasizing the importance of a long lipophilic side chain for inhibitory activity of the analogues studied.

A one-step synthesis of a deuterated paclitaxel analogue : 10-deacetoxy-(10α-2H)paclitaxel

Abstract 10-Deacetoxy-(10α- 2 H)paclitaxel was prepared in one step via the samarium diiodide mediated deoxygenation of paclitaxel in the presence of D 2 O.

The use of polymer-bound triphenylphosphine in the stereochemical inversion of secondary alcohols.

Polymer-bound triphenylphosphine can replace triphenylphosphine in the Mitsunobu reaction to generate stereochemically inverted secondary alcohols. This method is comparable with the standard Mitsunobu reaction in terms of inversion of stereochemistry, yield, and reaction time, even for sterically very hindered secondary alcohols. The special merit of this reaction is that the excess polymer-bound triphenylphosphine and its by-products are easily removed by filtration from the reaction products.

Design and synthesis of new cephalosporin antibiotics

Cephalosporins are important antibiotics. We synthesized new cephalosporin analogs containing novel side chains of methyl, propyl, benzyl, and phenoxy groups. Four synthetic methods with N-alkylation and N-acylation at position C-7 and esterification at position C-4 of 7-aminodesacetoxycephalosporanic acid are reported here.Graphical Abstract