The subject of this research is C-glycosides. These materials are sometimes found in medicinally active natural products, for example papulacandin (anti-fungal) and altromycin B (anti-tumor). There is also intense interest in C-glycosides as analogs of the more commonly found O-glycosides. If they were to be """"""""faithful"""""""" analogs, they could interfere in many natural processes normally reserved for O-glycosides with one major difference. C-glycosides would be stable and have a longer lifetime than inherently unstable and shorter-lived O-glycosides. The study of c_glycosides, in most cases, first requires their synthesis in the laboratory. This will be accomplished using a well-established method invented in 1940, but first recognized as useful for carbohydrate chemistry by the PI in 1997. Thus the Ramberg-Backlund reaction will be used to prepare C-glycoside analogs of daunomycin, a clinically active antitumor agent. The northwest sector of altromycin, a powerful antitumor drug, is a natural C-glycoside which has never been prepared in the lab. This is also a target. Further aims include the synthesis of C-glycolipids as analogs of known, bio-active O-glycolipids including KRN7000, an inducer of NK cells. Another aim of this project is the synthesis of C- glyco analogs of disaccharides which include the sialic acid residue. These materials will mimic O-glycosides involved in adhesion in to both respiratory and gastrointestinal epithelial cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM060271-04
Application #
6656978
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
2000-09-30
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2005-08-31
Support Year
4
Fiscal Year
2003
Total Cost
$332,603
Indirect Cost
Name
Hunter College
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
620127915
City
New York
State
NY
Country
United States
Zip Code
10065
Franck, Richard W (2012) C-Galactosylceramide: Synthesis and Immunology. C R Chim 15:46-56
Schmieg, John; Yang, Guangli; Franck, Richard W et al. (2010) A multifactorial mechanism in the superior antimalarial activity of alpha-C-GalCer. J Biomed Biotechnol 2010:283612
Parhi, Ajit K; Mootoo, David R; Franck, Richard W (2008) Synthesis of the Mixed Acetal Segment of S-Glyceroplasmalopsychosine. Tetrahedron 64:9821-9827
Pu, Jun; Franck, Richard W (2008) C-Galactosylceramide Diastereomers via Sharpless Asymmetric Epoxidation Chemistry. Tetrahedron 64:8618-8629
Chen, Guangwu; Chien, May; Tsuji, Moriya et al. (2006) E and Z alpha-C-galactosylceramides by Julia-Lythgoe-Kocienski chemistry: a test of the receptor-binding model for glycolipid immunostimulants. Chembiochem 7:1017-22
Schmieg, John; Yang, Guangli; Franck, Richard W et al. (2005) Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion. Proc Natl Acad Sci U S A 102:1127-32
Chen, Guangwu; Schmieg, John; Tsuji, Moriya et al. (2004) Efficient synthesis of alpha-C-galactosyl ceramide immunostimulants: use of ethylene-promoted olefin cross-metathesis. Org Lett 6:4077-80
Parhi, Ajit K; Franck, Richard W (2004) A Weinreb nitrile oxide and nitrone for cycloaddition. Org Lett 6:3063-5
Yang, Guangli; Schmieg, John; Tsuji, Moriya et al. (2004) The C-glycoside analogue of the immunostimulant alpha-galactosylceramide (KRN7000): synthesis and striking enhancement of activity. Angew Chem Int Ed Engl 43:3818-22
Pasetto, Paolo; Franck, Richard W (2003) Synthesis of both possible isomers of the northwest quadrant of altromycin B. J Org Chem 68:8042-60

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