Total Synthesis of a Densely Functionalized Plesiomonas shigelloides Serotype 51 Aminoglycoside Trisaccharide Antigen

Abstract

Plesiomonas shigelloides, a pathogen responsible for frequent outbreaks of severe travelers' diarrhea, causes grave extraintestinal infections. Sepsis and meningitis due to P. shigelloides are associated with a high mortality rate as antibiotic resistance increases and vaccines are not available. Carbohydrate antigens expressed by pathogens are often structurally unique and are targets for developing vaccines and diagnostics. Here, we report a total synthesis of the highly functionalized trisaccharide repeating unit 2 from P. shigelloides serotype 51 from three monosaccharides. A judicious choice of building blocks and reaction conditions allowed for the four amino groups adorning the sugar rings to be installed with two N-acetyl (Ac) groups, rare acetamidino (Am), and d-3-hydroxybutyryl (Hb) groups. The strategy for the differentiation of amino groups in trisaccharide 2 will serve well for the syntheses of other complex glycans.

Synthesis and Stereocontrolled Equatorially Selective Glycosylation Reactions of a Pseudaminic Acid Donor: Importance of the Side-Chain Conformation and Regioselective Reduction of Azide Protecting Groups

“…60 In the event, heating of 47 with thioacetic acid and lutidine in chloroform at reflux for 10 h yielded 68% of a single monoamide 50 arising from conversion of the side chain azide (Scheme 6). Subsequent treatment with 1,3-propanedithiol and triethylamine in wet pyridine 108 at room temperature followed by installation of a Boc group afforded the amido carbamate 51 in 72% yield. Finally, heating with aqueous barium hydroxide in dioxane followed by hydrogenolysis afforded the Pse glycoside 52 with the two amines differentially protected, one in the form of a tert -butylcarbamate suitable for selective cleavage and further elaboration (Scheme 6).…”

1‐Picolinyl‐5‐azido Thiosialosides: Versatile Donors for the Stereoselective Construction of Sialyl Linkages

“…In the donor design stage, the azido group in 2 was en‐visioned to be a versatile precursor for the amino group, thus the transformations of the azido group to the corresponding acetamido as well as glycolamido groups were investigated (Scheme ). Under the effect of thioacetic acid, the reduction and simultaneous acetylation of 14 was achieved, affording 45 efficiently (79 %). Similarly, methyl ester 42 was converted to 46 with comparable efficiency (73 %).…”

1‐Picolinyl‐5‐azido Thiosialosides: Versatile Donors for the Stereoselective Construction of Sialyl Linkages

“…In the donor design stage,t he azido group in 2 was envisioned to be aversatile precursor for the amino group,thus the transformations of the azido group to the corresponding acetamido as well as glycolamido groups were investigated (Scheme 3). Under the effect of thioacetic acid, [26] the reduction and simultaneous acetylation of 14 was achieved, affording 45 efficiently (79 %). Similarly,methyl ester 42 was converted to 46 with comparable efficiency(73 %).…”