Yuanyuan Jiang, Shichao Duan, Jiaming Li, Yanli Zhao, Jinsong Yang
{"title":"Sialyl Lewisa 四糖抗原的化学合成和化学酶合成。","authors":"Yuanyuan Jiang, Shichao Duan, Jiaming Li, Yanli Zhao, Jinsong Yang","doi":"10.1039/d4ob00809j","DOIUrl":null,"url":null,"abstract":"<p><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 1 structurally derived from sLe<sup>a</sup> are reported. Challenges involved in the chemical synthesis include the highly stereoselective construction of 1,2-<i>cis</i>-α-L-fucoside and α-D-sialoside, as well as the assembly of the 3,4-disubstituted <i>N</i>-acetylglucosamine subunit. Perbenzylated thiofucoside and <i>N</i>-acetyl-5-<i>N</i>,4-<i>O</i>-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-<i>O</i> and then 4-<i>O</i> 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.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chemical and chemoenzymatic syntheses of sialyl Lewis<sup>a</sup> tetrasaccharide antigen.\",\"authors\":\"Yuanyuan Jiang, Shichao Duan, Jiaming Li, Yanli Zhao, Jinsong Yang\",\"doi\":\"10.1039/d4ob00809j\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><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 1 structurally derived from sLe<sup>a</sup> are reported. Challenges involved in the chemical synthesis include the highly stereoselective construction of 1,2-<i>cis</i>-α-L-fucoside and α-D-sialoside, as well as the assembly of the 3,4-disubstituted <i>N</i>-acetylglucosamine subunit. Perbenzylated thiofucoside and <i>N</i>-acetyl-5-<i>N</i>,4-<i>O</i>-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-<i>O</i> and then 4-<i>O</i> 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.</p>\",\"PeriodicalId\":96,\"journal\":{\"name\":\"Organic & Biomolecular Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Organic & Biomolecular Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1039/d4ob00809j\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic & Biomolecular Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1039/d4ob00809j","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Chemical and chemoenzymatic syntheses of sialyl Lewisa tetrasaccharide antigen.
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.