Methodology for the synthesis of 2-deoxy-alpha-glycosides and studies directed towards the total synthesis of angelmicin B (hibarimicin B).

This dissertation describes research involving the development of methodology for the synthesis of 2-deoxy-alpha-glycosides, as well as studies aimed at a total synthesis of the antitumor natural product angelmicin B. Specifically, 2-deoxy-2-iodomanno- and talopyranosyl acetates (glycosyl acetates bearing an axial C(2) iodide substituent) were shown to be effective donors for alpha-selective glycosidation reaction. A new method for the iodoacetoxylation of glycals involving cerium(IV) ammonium nitrate, sodium iodide and acetic acid was also developed, which provides the alpha- manno iodoacetates in >9:1 selectivity in most cases. These studies are the subject of Chapter I. Background information on angelmicin B, including structural and biological studies is described in Chapter II. Chapter II also comprises a brief review of various methods for the construction of biaryl bonds in natural product synthesis. Our efforts towards the development of a strategy for the construction of the D-D' biaryl linkage of angelmicin B are described in Chapters III and IV. An intramolecular oxidative coupling approach could not be successfully developed as a viable synthetic strategy. In particular the conditions required to promote such a bond forming reaction are too harsh to be compatible with late stage synthetic intermediates. However, the palladium (0) mediated coupling of a C'D' metal derivative with a CD naphthoquinone halide can be carried out under mild conditions. This latter coupling strategy may be viable for use in the total synthesis.Ph.D.Organic chemistryPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/123453/2/3079508.pd