Although many synthetic and biological transformations involve oxocarbenium ion intermediates, details about the structure and reactivity of these highly reactive species remain unknown. For example, debate continues about the preferred conformation of the mannosyl cation, although drugs targeting this cation have been tested to treat genetic and viral diseases as well as cancer. In other cases, inconsistencies in the literature remain, such as the nature of anchimeric assistance in stereoselective glycosylation. This proposal builds upon our work during the last funding period that demonstrates the influence of heteroatom substituents on the conformations of oxocarbenium ions and thus the stereoselectivity of their reactions. We have devised an approach to solving the structure of the mannosyl cation, and we will gain insight into the nature of anchimeric assistance. We have also devised new stereoselective synthetic methods based upon oxocarbenium and peroxocarbenium ion intermediates. This proposal will have considerable implications for public health. For example, our studies on the three- dimensional structures of carbohydrate-derived intermediates will impact the design of drugs for the treatment of diabetes, hepatitis, HIV, and cancer. In addition, our studies on the structure and reactivity of these intermediates will enable chemists to prepare those drugs more efficiently.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061066-12
Application #
8309824
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
2000-04-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
12
Fiscal Year
2012
Total Cost
$299,963
Indirect Cost
$97,013
Name
New York University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
Kendale, Joanna C; Valentín, Elizabeth M; Woerpel, K A (2014) Solvent effects in the nucleophilic substitutions of tetrahydropyran acetals promoted by trimethylsilyl trifluoromethanesulfonate: trichloroethylene as solvent for stereoselective C- and O-glycosylations. Org Lett 16:3684-7
Otte, Douglas A L; Borchmann, Dorothee E; Lin, Chin et al. (2014) 13C NMR spectroscopy for the quantitative determination of compound ratios and polymer end groups. Org Lett 16:1566-9
Lavinda, Olga; Tran, Vi Tuong; Woerpel, K A (2014) Effect of conformational rigidity on the stereoselectivity of nucleophilic additions to five-membered ring bicyclic oxocarbenium ion intermediates. Org Biomol Chem 12:7083-91
Tran, Vi Tuong; Woerpel, K A (2013) Nucleophilic addition to silyl-protected five-membered ring oxocarbenium ions governed by stereoelectronic effects. J Org Chem 78:6609-21
Dibble, David J; Ziller, Joseph W; Woerpel, K A (2011) Spectroscopic and X-ray crystallographic evidence for electrostatic effects in 4-substituted cyclohexanone-derived hydrazones, imines, and corresponding salts. J Org Chem 76:7706-19
Beaver, Matthew G; Woerpel, K A (2010) Erosion of stereochemical control with increasing nucleophilicity: O-glycosylation at the diffusion limit. J Org Chem 75:1107-18
Krumper, Jennifer R; Salamant, Walter A; Woerpel, K A (2009) Correlations between nucleophilicities and selectivities in the substitutions of tetrahydropyran acetals. J Org Chem 74:8039-50
Yang, Michael T; Woerpel, K A (2009) The effect of electrostatic interactions on conformational equilibria of multiply substituted tetrahydropyran oxocarbenium ions. J Org Chem 74:545-53
Ramirez, Armando P; Thomas, Andrew M; Woerpel, K A (2009) Preparation of bicyclic 1,2,4-trioxanes from gamma,delta-unsaturated ketones. Org Lett 11:507-10
Harris, Jason R; Waetzig, Shelli R; Woerpel, K A (2009) Palladium(II)-catalyzed cyclization of unsaturated hydroperoxides for the synthesis of 1,2-dioxanes. Org Lett 11:3290-3

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