Synthesis of Three Essential Components of Salmycin: D-hexo-, D-heptopyranoses and Danoxamine

Abstract

Desferrisalmycin B exhibits potent growth inhibitory activity against Gram-positive organisms including multidrug resistant strains. The compound contains a danoxamine, a D-arabino-hexopyranos-2-ulose, and a 6-deoxy-6-(methylamino)-D-gluco-heptopyranose. The stereoselective synthesis of 6-deoxy-6-(methylamino)-D-gluco-heptopyranosyl building block is challenge of total synthesis desferrisalmycin B. In previous study, 6-deoxy-6-(methylamino)-D-gluco-heptopyranosyl building block was synthesized indirectly from a heptoglucopyranosyl precursor. However, the stereochemical control for the introduction of the C6 hydroxyl is moderate. We developed a new approach for the stereoselective synthesis of heptoglycosides from hexosugar substrates. The stereoselectivity comes from the use of an asymmetric hydroxylation method. In the thesis, we speculate that it should be possible to apply the asymmetric amination or hydroxylation method to obtain the desired 6-deoxy-6-(methylamino)-D-gluco-heptopyranosyl building block from a D-glucose. The methods synthesize the key building block with high chiral purity, and they would be useful for the assembly of Salmycins.

Desferrisalmycin B exhibits potent growth inhibitory activity against Gram-positive organisms including multidrug resistant strains. The compound contains a danoxamine, a D-arabino-hexopyranos-2-ulose, and a 6-deoxy-6-(methylamino)-D-gluco-heptopyranose. The stereoselective synthesis of 6-deoxy-6-(methylamino)-D-gluco-heptopyranosyl building block is challenge of total synthesis desferrisalmycin B. In previous study, 6-deoxy-6-(methylamino)-D-gluco-heptopyranosyl building block was synthesized indirectly from a heptoglucopyranosyl precursor. However, the stereochemical control for the introduction of the C6 hydroxyl is moderate. We developed a new approach for the stereoselective synthesis of heptoglycosides from hexosugar substrates. The stereoselectivity comes from the use of an asymmetric hydroxylation method. In the thesis, we speculate that it should be possible to apply the asymmetric amination or hydroxylation method to obtain the desired 6-deoxy-6-(methylamino)-D-gluco-heptopyranosyl building block from a D-glucose. The methods synthesize the key building block with high chiral purity, and they would be useful for the assembly of Salmycins.