Nicole L. Snyder

Carbohydrate-based oxepines: ring expanded glycals for the synthesis of septanose saccharides

A ring-closing metathesis (RCM) approach to a family of carbohydrate-based oxepines is described. A variety of readily accessible, protected monosaccharide derived dienes were used to demonstrate the utility of the synthetic sequence and to investigate how factors such as rigidification and deoxygenation mediate RCM using the Grubbs or Schrock catalyst. The seven-membered cyclic enol ethers are ring expanded glycals to be used in the synthesis of septanose carbohydrates.

Asymmetric Co(II)-Catalyzed Cyclopropanation with Succinimidyl Diazoacetate: General Synthesis of Chiral Cyclopropyl Carboxamides

[Co(P1)] is an effective catalyst for asymmetric cyclopropanation with succinimidyl diazoacetate. The Co(II)-catalyzed reaction is suitable for various olefins, providing the desired cyclopropane succinimidyl esters in high yields and excellent diastereo- and enantioselectivity. The resulting enantioenriched cyclopropane succinimidyl esters can serve as convenient synthons for the general synthesis of optically active cyclopropyl carboxamides.

Stereoselectivity in the Epoxidation of Carbohydrate-Based Oxepines

The facial selectivity in the DMDO epoxidation of carbohydrate-based oxepines derived from glucose, galactose, and mannose has been determined by product analysis and density functional theory (DFT, B3LYP/6-31+G**//B3LYP/6-31G*) calculations. Oxepines 3 and 4, derived from d-galactose and d-mannose, largely favor alpha- over beta-epoxidation. The results reported here, along with selectivities in the DMDO-mediated epoxidation of d-xylose-based oxepine 1 and d-glucose-based oxepines 2 and 5 reported earlier, support a model in which electronic effects, guided by the stereochemistry of the oxygens on the oxepine ring, largely determine the stereoselectivity of epoxidation. Other contributing factors included conformational issues in the oxepines transition state relative to the reactant, the asynchronicity in bond formation of the epoxide, and the overall steric bulk on the alpha- and beta-faces of the oxepine. Considered together, these factors should generally predict facial selectivity in the DMDO-epoxidation of cyclic enol ethers.

Toward Orthogonal Preparation of Sequence-Defined Monodisperse Heteromultivalent Glycomacromolecules on Solid Support Using Staudinger Ligation and Copper-Catalyzed Click Reactions

The investigation of heteromultivalent interactions of complex glycoligands and proteins is critical for understanding important biological processes and developing carbohydrate-based pharmaceutics. Synthetic glycomimetics, derived by mimicking complex glycoligands on a variety of scaffolds, have become important tools for studying the role of carbohydrates in chemistry and biology. In this paper, we report on a new synthetic strategy for the preparation of monodisperse, sequence-defined glycooligomers or so-called precision glycomacromolecules based on solid phase oligomer synthesis and the Staudinger ligation. This strategy employs a solid-supported synthetic approach using a novel carboxy-functionalized building block which bears a functional handle required for Staudinger ligation on solid support. Furthermore, we combined Staudinger ligation and copper catalyzed azide alkyne cycloaddition (CuAAC) reactions to synthesize heteromultivalent glycooligomers on solid support for the first time, demonstrating the utility of this approach for the synthesis of heterofunctional glycomacromolecules.