<i>De Novo</i> Synthesis of the Bacterial 2-Amino-2,6-Dideoxy Sugar Building Blocks d‑Fucosamine, d‑Bacillosamine, and d‑Xylo-6-deoxy-4-ketohexosamine

The cell-surface glycans on bacteria contain many monosaccharides that cannot be obtained by isolation from natural sources. Availability of differentially protected monosaccharides is therefore often limiting access to potential oligosaccharide vaccine antigens. d-Fucosamine, d-bacillosamine, and d-xylo-2,6-deoxy-4-ketohexosamine building blocks were prepared via a divergent <i>de novo</i> synthesis from l-Garner aldehyde. The route relies on a chelation-control assisted organometallic addition and an <i>anti</i>-selective dihydroxylation reaction

<i>De Novo</i> Synthesis of the Bacterial 2-Amino-2,6-Dideoxy Sugar Building Blocks d‑Fucosamine, d‑Bacillosamine, and d‑Xylo-6-deoxy-4-ketohexosamine

The cell-surface glycans on bacteria contain many monosaccharides that cannot be obtained by isolation from natural sources. Availability of differentially protected monosaccharides is therefore often limiting access to potential oligosaccharide vaccine antigens. d-Fucosamine, d-bacillosamine, and d-xylo-2,6-deoxy-4-ketohexosamine building blocks were prepared via a divergent <i>de novo</i> synthesis from l-Garner aldehyde. The route relies on a chelation-control assisted organometallic addition and an <i>anti</i>-selective dihydroxylation reaction

<i>De Novo</i> Synthesis of the Bacterial 2-Amino-2,6-Dideoxy Sugar Building Blocks d‑Fucosamine, d‑Bacillosamine, and d‑Xylo-6-deoxy-4-ketohexosamine

The cell-surface glycans on bacteria contain many monosaccharides that cannot be obtained by isolation from natural sources. Availability of differentially protected monosaccharides is therefore often limiting access to potential oligosaccharide vaccine antigens. d-Fucosamine, d-bacillosamine, and d-xylo-2,6-deoxy-4-ketohexosamine building blocks were prepared via a divergent <i>de novo</i> synthesis from l-Garner aldehyde. The route relies on a chelation-control assisted organometallic addition and an <i>anti</i>-selective dihydroxylation reaction

Total Synthesis of Legionaminic Acid as Basis for Serological Studies

Legionaminic acid is a nine-carbon diamino monosaccharide that is found coating the surface of various bacterial human pathogens. Its unique structure makes it a valuable biological probe, but access via isolation is difficult and no practical synthesis has been reported. We describe a stereoselective synthesis that yields a legionaminic acid building block as well as linker-equipped conjugation-ready legionaminic acid starting from cheap d-threonine. To set the desired amino and hydroxyl group pattern of the target, we designed a concise sequence of stereoselective reactions. The key transformations rely on chelation-controlled organometallic additions and a Petasis multicomponent reaction. The legionaminic acid was synthesized in a form that enables attachment to surfaces. Glycan microarray containing legionaminic acid revealed that human antibodies bind the synthetic glycoside. The synthetic bacterial monosaccharide is a valuable probe to detect an immune response to bacterial pathogens such as Legionella pneumophila, the causative agent of Legionnaire’s disease

<i>De Novo</i> Synthesis of l-Colitose and l-Rhodinose Building Blocks

A divergent, practical, and efficient <i>de novo</i> synthesis of fully functionalized l-colitose (3,6-dideoxy-l-galactose), 2-<i>epi</i>-colitose (3,6-dideoxy-l-talose), and l-rhodinose (2,3,6-trideoxy-l-galactose) building blocks has been achieved using inexpensive, commercially available (<i>S</i>)-ethyl lactate as the starting material. The routes center around a diastereoselective Cram-chelated allylation that provides a common homoallylic alcohol intermediate. Oxidation of this common intermediate finally resulted in the synthesis of the three monosaccharide building blocks

Homogeneous Gold-Catalyzed Glycosylations in Continuous Flow

The use of versatile alkynyl-building blocks that are activated by gold­(I)-catalysis is demonstrated to efficiently generate a variety of glycosides in continuous flow. The application of a continuous flow setting to gold­(I)-catalyzed glycosylations enables very short reaction times and excellent control of the reaction conditions

Total Synthesis of Legionaminic Acid as Basis for Serological Studies

Legionaminic acid is a nine-carbon diamino monosaccharide that is found coating the surface of various bacterial human pathogens. Its unique structure makes it a valuable biological probe, but access via isolation is difficult and no practical synthesis has been reported. We describe a stereoselective synthesis that yields a legionaminic acid building block as well as linker-equipped conjugation-ready legionaminic acid starting from cheap d-threonine. To set the desired amino and hydroxyl group pattern of the target, we designed a concise sequence of stereoselective reactions. The key transformations rely on chelation-controlled organometallic additions and a Petasis multicomponent reaction. The legionaminic acid was synthesized in a form that enables attachment to surfaces. Glycan microarray containing legionaminic acid revealed that human antibodies bind the synthetic glycoside. The synthetic bacterial monosaccharide is a valuable probe to detect an immune response to bacterial pathogens such as Legionella pneumophila, the causative agent of Legionnaire’s disease

Chemoselective Photoredox Synthesis of Unprotected Primary Amines Using Ammonia

Unprotected α-amino carbon radicals are produced as novel intermediates via a transformation that merges acid-promoted N–H imine generation and chemoselective photocatalytic single-electron reduction. Coupling ammonia and aldehydes/ketones allows the generation of primary amines under mild conditions without the need for protecting groups. The key intermediate can be efficiently transformed into primary (di)­amines by a formal dimerization, reductive amination via hydrogen atom transfer, and arylation through radical–radical coupling

Visible-Light-Mediated Achmatowicz Rearrangement

Visible-light-mediated photoredox catalysis is a viable method to access highly reactive intermediates from cheap, readily available, and shelf-stable reagents to perform clean chemical transformations. Here, we report the first photoredox-catalyzed Achmatowicz reaction of furfuryl alcohol derivatives to produce functionalized dihydropyranones while only forming easily separable NaHSO₄ as a byproduct. The water solubility of the byproduct facilitates direct Boc-protection of the resulting hemiacetal without the need for column purification. The reaction is very robust and permits the use of various aqueous solutions and light sources including sunlight

Determining Substrate Specificities of β1,4-Endogalactanases Using Plant Arabinogalactan Oligosaccharides Synthesized by Automated Glycan Assembly

Pectin is a structurally complex plant polysaccharide with many industrial applications in food products. The structural elucidation of pectin is aided by digestion assays with glycosyl hydrolases. We report the automated glycan assembly of oligosaccharides related to the arabinogalactan side chains of pectin as novel biochemical tools to determine the substrate specificities of endogalactanases. Analysis of the digestion products revealed different requirements for the lengths and arabinose substitution pattern of the oligosaccharides to be recognized and hydrolyzed by the galactanases