Conioidine A (1), isolated in 1993 with unknown relative and absolute configuration, was suggested to be a DNA-binding compound by an indirect technique. Four stereoisomers of conioidine A have been synthesized from D-and L-proline, and the natural product has been identified as possessing (4R,6R) absolute configuration. Binding of the conioidine diastereomers to calf thymus DNA (CT DNA) and human serum albumin (HSA) has been investigated by fluorescence spectroscopy and isothermal titration calorimetry (ITC). All stereoisomers display at least an order of magnitude weaker binding to DNA than the control compound netropsin; however, a strong association with HSA was observed for the (4R,6S) stereoisomer.

Monomeric, dimeric, and trimeric derivatives of the triphenylmethane dye crystal violet (1a -1f) have been synthesized for the purpose of evaluating their affinity and sequence selectivity for duplex DNA. Competitive ethidum displacement assays indicate that 1a -1f have apparent association constants for CT DNA in the range of 1.80-16.2 ×107 M-1 and binding site sizes of 10-14 bp. Viscosity experiments performed on ligand 1f confirmed that these dyes associate with duplex DNA by a non-intercalative mode of binding. Circular dichroism and competition binding studies of the tightest binding ligand 1e with known major and minor groove binding molecules suggest that these dye derivatives likely occupy the major groove of DNA. Data from the binding of 1e to polynucleotides indicate close to an order of magnitude preference for associating with AT rich homopolymers over GC rich homopolymers, suggesting a shapeselective match of the sterically bulky ligand with DNA containing a wider major groove.

CHAPTER 2: METHODOLOGY IN ANTHRONE C-GLYCOSIDE SYNTHESIS 2.1 Introduction………………………………………………………..……………..……8 2.2 Alkylation of anthrones………..……………………………………………………....8 2.3 In-vitro biosynthesis of the C-glycosidic bond in aloin …………………...….………8 2.4 Total synthesis of cassialoin……………………………….…………………..……...9 CHAPTER 3: SYNTHESIS OF ALVARADOINS E & F, UVEOSIDE, AND 10-EPI-UVEOSIDE 3.1 Introduction…………………………………………..………....………………...…11 3.2 Objectives and retrosynthetic analysis ………...…………………………….………12 3.3 Synthesis of fragment 8……………………………………………………...………13 3.4 Synthesis of fragment 9a…………………………………………………….………13 3.5 Model studies for the formation of anthrone-C-glycoside……...…..……….………14 3.6 Formation of carboxylic acid intermediate ………………………………………….17 3.7 Conversion to anomeric acetate………………………………………….…………..18 3.8 Hydrolysis of isobutyrate and acetate esters…………………………………………20 vi 3.9 Completion of the synthesis of alvaradoins E and F…..……………………………..21 3.10 Completion of the synthesis of uveoside and 10-epi-uveoside……………...……...22 CHAPTER 4: CONCLUSION …………………………………….

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