The polyketide-derived C-aryl glycoside natural products have a variety of interesting biological activities, most notably antitumor activity. There is considerable variety in the structures of both the aglycone and the sugar moieties of these compounds. Our ability to modify these functionally complex naturally occurring materials is limited; furthermore, the natural products are difficult to obtain. Therefore, synthesis is not only intellectually challenging, it is also essential for the study of structure-activity relationships. Recognizing the potential importance of compounds with the aryl C-glycoside structural feature, we are driven by the following goals: (1) to develop new strategies and efficient methods for the synthesis of C-aryl glycosides and for the preparation of polycyclic aromatic systems with control of substitution pattern; (2) to demonstrate new strategies and methods by application to the synthesis of natural products; (3) to take advantage of efficient sequences to prepare new C-aryl glycosides with the eventual goal of developing a structure-activity picture for the C-aryl glycoside antibiotics. Our experience with quinone chemistry led us to consider a """"""""reverse polarity"""""""" or """"""""umpolung"""""""" approach to the synthesis of C-aryl glycosides. This approach has produced methodology which establishes the functional group patterns required for preparation of members of all four structural classes of these antibiotics. We have recently completed a synthesis of ent-C104 and are close to the completion of a synthesis of papulacandin D. These compounds represent two of the major structural classes of aryl C-glycosides. During the period which corresponds to this proposal, we plan to apply our new methodology to the synthesis of deacetylravidomycin and kidamycin, representatives of the remaining two major classes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA087503-05
Application #
6633788
Study Section
Special Emphasis Panel (ZRG1-SSS-A (02))
Program Officer
Lees, Robert G
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2005-06-30
Support Year
5
Fiscal Year
2003
Total Cost
$169,313
Indirect Cost
Name
State University New York Stony Brook
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Parker, Kathlyn A; Mindt, Thomas L (2011) Convergent Synthesis of 2H-Chromenes - a Formal [3+3] Cycloaddition by a One-pot, Three-Step Cascade. Tetrahedron 67:9779-9786
Cao, Huanyan; Parker, Kathlyn A (2008) Short synthesis of the C1-C14 stretch of discodermolide from building blocks prepared by asymmetric catalysis. Org Lett 10:1353-6
Parker, Kathlyn A; Wang, Peng (2007) Deconstruction-reconstruction strategy for accessing valuable polyketides. Preparation of the C15-C24 stereopentad of discodermolide. Org Lett 9:4793-6
Lee, Jae Chul; Parker, Kathlyn A; Sampson, Nicole S (2006) Amino acid-bearing ROMP polymers with a stereoregular backbone. J Am Chem Soc 128:4578-9
Parker, Kathlyn A; Cao, Huanyan (2006) Scalable, catalytic asymmetric synthesis of syn, anti stereotriad building blocks for polypropionate antibiotics. Org Lett 8:3541-4
Parker, Kathlyn A; Mindt, Thomas L; Koh, Yung-hyo (2006) TESOTf-induced rearrangement of quinols. Efficient construction of the fully functionalized carbon skeleton of the griseusins by a divergent-reconvergent approach. Org Lett 8:1759-62
Parker, Kathlyn A; Wang, Zhongyu (2006) Cleavable chiral auxiliaries in 8pi (8pi, 6pi) electrocyclizations. Org Lett 8:3553-6
Parker, Kathlyn A; Chang, Wonsuk (2005) Regioselectivity of rhodium nitrene insertion. Syntheses of protected glycals of l-daunosamine, d-saccharosamine, and l-ristosamine. Org Lett 7:1785-8
Parker, Kathlyn A; Chang, Wonsuk (2003) A synthesis of L-vancosamine derivatives from non-carbohydrate precursors by a short sequence based on the Marshall, McDonald, and Du Bois reactions. Org Lett 5:3891-3
Parker, Kathlyn A; Mindt, Thomas L (2002) Heterocycle annulation of enolizable vinyl quinone imides. Dihydroquinolines and quinolines from thermal 6pi-electrocyclizations and indoles from photochemical cyclizations. Org Lett 4:4265-8

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