{"title":"Chemical and chemoenzymatic syntheses of sialyl Lewisa tetrasaccharide antigen†","authors":"","doi":"10.1039/d4ob00809j","DOIUrl":null,"url":null,"abstract":"<div><p>Sialyl Lewis<sup>a</sup> (sLe<sup>a</sup>), also known as cancer antigen 19-9, is a tumor-associated carbohydrate antigen. In this article, chemical and chemoenzymatic syntheses of a tetrasaccharide glycan <strong>1</strong> structurally derived from sLe<sup>a</sup> are reported. Challenges involved in the chemical synthesis include the highly stereoselective construction of 1,2-<em>cis</em>-α-<span>l</span>-fucoside and α-<span>d</span>-sialoside, as well as the assembly of the 3,4-disubstituted <em>N</em>-acetylglucosamine subunit. Perbenzylated thiofucoside and <em>N</em>-acetyl-5-<em>N</em>,4-<em>O</em>-oxazolidinone protected sialic acid thioglycoside were employed as glycosyl donors, respectively, for the efficient preparation of the desired α-fucoside and α-sialoside. The 3,4-branched glucosamine backbone was established through a 3-<em>O</em> and then 4-<em>O</em> glycosylation sequence in which the 3-hydroxyl group of the glucosamine moiety was glycosylated first and then the 4-hydroxyl. A facile chemoenzymatic approach was also exploited to synthesize the target molecule. The chemically obtained free disaccharide <strong>30</strong> was sequentially sialylated and fucosylated in an enzyme-catalyzed regio- and stereospecific manner to form <strong>1</strong> in high yields. The linker appended <strong>1</strong> can be covalently attached to a carrier protein for further immunological studies.</p></div>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic & Biomolecular Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/org/science/article/pii/S1477052024005688","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
Sialyl Lewisa (sLea), also known as cancer antigen 19-9, is a tumor-associated carbohydrate antigen. In this article, chemical and chemoenzymatic syntheses of a tetrasaccharide glycan 1 structurally derived from sLea are reported. Challenges involved in the chemical synthesis include the highly stereoselective construction of 1,2-cis-α-l-fucoside and α-d-sialoside, as well as the assembly of the 3,4-disubstituted N-acetylglucosamine subunit. Perbenzylated thiofucoside and N-acetyl-5-N,4-O-oxazolidinone protected sialic acid thioglycoside were employed as glycosyl donors, respectively, for the efficient preparation of the desired α-fucoside and α-sialoside. The 3,4-branched glucosamine backbone was established through a 3-O and then 4-O glycosylation sequence in which the 3-hydroxyl group of the glucosamine moiety was glycosylated first and then the 4-hydroxyl. A facile chemoenzymatic approach was also exploited to synthesize the target molecule. The chemically obtained free disaccharide 30 was sequentially sialylated and fucosylated in an enzyme-catalyzed regio- and stereospecific manner to form 1 in high yields. The linker appended 1 can be covalently attached to a carrier protein for further immunological studies.