The synthesis of 3'-sugar -modified nucleoside analogs related to oxetanocin.

The total synthetic approaches to three classes of sugar-modified compounds, analogs of oxetanocin A, 3$\sp \prime $-deoxy-3$\sp \prime $-hydroxymethyl- and 2$\sp \prime $,3$\sp \prime $-dideoxy-3$\sp \prime $-hydroxymethyl-ribofuranosides, were initiated due to problems involved with the reported synthetic methodologies of these compounds. Initial attempts at the synthesis of a properly substituted sugar, that would facilitate the synthesis of oxetanocin analogs, involved the addition of the requisite hydroxymethyl substituent by employing the Wittig reaction. Subsequent transformations yielded the known triol 5-O-benzyl-3-deoxy-3-(benzyloxy)methyl-D-ribitol which could be converted to an oxetanose sugar via reported methodology. An intermediate in the attempt at the synthesis of oxetanocin was 5-O-benzoyl-3-deoxy-3-(benzyloxy)methyl-1,2-O-isopropylidene-$ \alpha $-D-ribofuranose which was converted to the 3$\sp \prime $-branched carbohydrate 1,2,5-tri-O-benzoyl-3-deoxy-3-(benzyloxy)methyl-$ \alpha $,$\beta $-D-ribofuranose. The synthetic utility of this sugar was demonstrated by the synthesis of a number of 3$\sp \prime $-deoxy-3$\sp \prime $-hydroxymethyl ribofuranosides. Several synthetic approaches for the synthesis of 2$\sp \prime $,3$\sp \prime $-dideoxy-3$\sp \prime $-branched ribosides are described. The first carbohydrate synthesized was 5-O-benzoyl-3-deoxy-3-(benzyloxy)methyl-2-O-t-butyldimethylsilyl-1-O-methyl-$\beta $-D-ribofuranose. Due to the lengthy synthetic sequence, when this compound was employed, two additional 2,3-dideoxy-3-branched sugars were synthesized, 5-O-benzoyl-2,3-dideoxy-3-(benzyloxy)methyl-1-O-methyl-$ \beta $-D- and 1,5-O-benzoyl-3-deoxy-3-(benzyloxy)methyl-$ \alpha $,$\beta $-D-ribofuranose. These compounds could then be condensed with a series of aglycones. Due to problems with poor glycosylation yields and mixtures of anomeric products in the previously described routes, another more facile route for the synthesis of 2$\sp \prime $,3$\sp \prime $-dideoxy-3-hydroxymethyl nucleosides was designed. A selective removal of the 2$\sp \prime $-benzoyl group of a protected 3$\sp \prime $-branched-riboside compound provided the 2$\sp \prime $-deprotected compounds which could be subsequently deoxygenated selectively. The utility of this approach was demonstrated in the synthesis of a series of branched nucleosides.PhDUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/105428/1/9124082.pdfDescription of 9124082.pdf : Restricted to UM users only