Synthesis of 3, 3???-di-O-methyl ardimerin

Includes bibliographical references (pages 82-87)C-aryl glycosides are part of the glycosyl arene family derived from Streptomyces bacteria1. The potential of C-aryl glycoside natural products as therapeutic agents stem from their antibiotic, antimicrobial, and antitumor biological activities2. Their framework provides a scaffold for potential drug candidates and hence numerous and thorough studies in their synthesis (both methodology and total synthesis) have been published in the past few decades. The defining feature of the C-aryl glycoside class of natural products is the carbon-carbon bond that holds a carbohydrate moiety and an aromatic aglycone (non-sugar group) together. This connectivity offers the substrate resistance to both enzymatic and hydrolytic cleavage. It is this essential stability that allows for C-aryl glycosides to navigate the plasma membrane to target and manipulate cellular DNA3. Selective DNA binding can occur by thread-like intercalation of base pairs by the planar aromatic system and non-covalent interactions of the major and minor DNA grooves by the carbohydrate group. This dual function of C-aryl glycosides can effectively induce structural modification of DNA4. The total synthesis of 3,3???-di-O-methyl ardimerin, a derivative of the natural product ardimerin (isolated from the herb Ardisia japonica)5 is described. The synthesis of 3,3'-di-O-methyl ardimerin is focused primarily on two main themes: (1) Formation of the C-aryl glycosidic bond and (2) Yamaguchi derived conditions for diolide formation. Future research is targeted in accessing the full structure of the natural product ardimerin by revisiting a substrate prior to diolide formation with an early demethylation utilizing MgI2