Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Mar 5;57(11):2929-2933.
doi: 10.1002/anie.201712022. Epub 2018 Feb 14.

A Diazido Mannose Analogue as a Chemoenzymatic Synthon for Synthesizing Di-N-acetyllegionaminic Acid-Containing Glycosides

Abhishek Santra  1 , An Xiao  1 , Hai Yu  1 , Wanqing Li  1 , Yanhong Li  1 , Linh Ngo  1 , John B McArthur  1 , Xi Chen  1
Affiliations

A Diazido Mannose Analogue as a Chemoenzymatic Synthon for Synthesizing Di-N-acetyllegionaminic Acid-Containing Glycosides

Abhishek Santra et al. Angew Chem Int Ed Engl. .

Abstract

A chemoenzymatic synthon was designed to expand the scope of the chemoenzymatic synthesis of carbohydrates. The synthon was enzymatically converted into carbohydrate analogues, which were readily derivatized chemically to produce the desired targets. The strategy is demonstrated for the synthesis of glycosides containing 7,9-di-N-acetyllegionaminic acid (Leg5,7Ac2 ), a bacterial nonulosonic acid (NulO) analogue of sialic acid. A versatile library of α2-3/6-linked Leg5,7Ac2 -glycosides was built by using chemically synthesized 2,4-diazido-2,4,6-trideoxymannose as a chemoenzymatic synthon for highly efficient one-pot multienzyme (OPME) sialylation followed by downstream chemical conversion of the azido groups into acetamido groups. The syntheses required 10 steps from commercially available d-fucose and had an overall yield of 34-52 %, thus representing a significant improvement over previous methods. Free Leg5,7Ac2 monosaccharide was also synthesized by a sialic acid aldolase-catalyzed reaction.

Keywords: carbohydrates; chemoenzymatic synthesis; glycosylation; legionaminic acid; sialic acid.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structures of 5,7-di-N-acetyllegionaminic acid (Leg5,7Ac2, 1), legionaminic acid (Leg, 2), N-acetylneuraminic acid (Neu5Ac, 3), and 2,4-diacetamido-2,4,6-trideoxy-D-mannose (6deoxyManNAc4NAc, 4) which is the six-carbon biosynthetic precursor of Leg5,7Ac2 (1).
Figure 2
Figure 2
Structures of Leg5,7Ac2α2–3LacβProN3 (25) and Leg5,7Ac2α2–6LacβProN3 (26).
Scheme 1
Scheme 1
Chemical synthesis of 6deoxyManNAc4NAc (4) from commercially available D-fucose (5) via a diazido intermediate 2,4-diazido-2,4,6-trideoxy mannose (6deoxyMan2,4diN3, 9).
Scheme 2
Scheme 2
PmAldolase-catalyzed synthesis of Leg5,7Ac2 (1) from 6deoxyManNAc4NAc (4) and sodium pyruvate.
See this image and copyright information in PMC

References

    1. Lewis AL, Desa N, Hansen EE, Knirel YA, Gordon JI, Gagneux P, Nizet V, Varki A. Proc Natl Acad Sci U S A. 2009;106:13552–13557. - PMC - PubMed
    2. Chen X, Varki A. ACS Chem Biol. 2010;5:163–176. - PMC - PubMed
    1. Hashii N, Isshiki Y, Iguchi T, Hisatsune K, Kondo S. Carbohydr Res. 2003;338:1055–1062. - PubMed
    2. Knirel YA, Shashkov AS, Tsvetkov YE, Jansson PE, Zahringer U. Adv Carbohydr Chem Biochem. 2003;58:371–417. - PubMed
    1. Schoenhofen IC, Young NM, Gilbert M. Methods Enzymol. 2017;597:187–207. - PubMed
    1. Hashii N, Isshiki Y, Iguchi T, Kondo S. Carbohydr Res. 2003;338:1063–1071. - PubMed
    2. MacLean LL, Vinogradov E, Pagotto F, Perry MB. Carbohydr Res. 2011;346:2589–2594. - PubMed
    3. Sun Y, Arbatsky NP, Wang M, Shashkov AS, Liu B, Wang L, Knirel YA. FEMS Immunol Med Microbiol. 2012;66:323–333. - PubMed
    4. Filatov AV, Wang M, Wang W, Perepelov AV, Shashkov AS, Wang L, Knirel YA. Carbohydr Res. 2014;392:21–24. - PubMed
    5. Kodali S, Vinogradov E, Lin F, Khoury N, Hao L, Pavliak V, Jones CH, Laverde D, Huebner J, Jansen KU, Anderson AS, Donald RG. J Biol Chem. 2015;290:19512–19526. - PMC - PubMed
    6. Vinogradov E, Maclean L, Xu HH, Chen W. Carbohydr Res. 2014;390:42–45. - PubMed
    7. Shashkov AS, Kenyon JJ, Senchenkova SN, Shneider MM, Popova AV, Arbatsky NP, Miroshnikov KA, Volozhantsev NV, Hall RM, Knirel YA. Glycobiology. 2016;26:501–508. - PubMed
    8. Shashkov AS, Senchenkova SN, Popova AV, Mei Z, Shneider MM, Liu B, Miroshnikov KA, Volozhantsev NV, Knirel YA. Russian Chem Bull Int Ed. 2015;64:1196–1199.
    1. Tsvetkov YE, Shashkov AS, Knirel YA, Zahringer U. Carbohydr Res. 2001;331:233–237. - PubMed

Publication types