Synthesis of fluoro- and seleno-containing D-lactose and D-galactose analogues,Organic & Biomolecular Chemistry

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Synthesis of fluoro- and seleno-containing D-lactose and D-galactose analogues
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2023-02-27 , DOI: 10.1039/d2ob02299k
Cecilia Romanò ₁ , Dennis Bengtsson ₁ , Angela Simona Infantino ₁ , Stefan Oscarson ₁

Affiliation

Synthetic deoxy-fluoro-carbohydrate derivatives and seleno-sugars are useful tools in protein–carbohydrate interaction studies using nuclear magnetic resonance spectroscopy because of the presence of the ¹⁹F and ⁷⁷Se reporter nuclei. Seven saccharides containing both these atoms have been synthesized, three monosaccharides, methyl 6-deoxy-6-fluoro-1-seleno-β-D-galactopyranoside (1) and methyl 2-deoxy-2-fluoro-1-seleno-α/β-D-galactopyranoside (2α and 2β), and four disaccharides, methyl 4-O-(β-D-galactopyranosyl)-2-deoxy-2-fluoro-1-seleno-β-D-glucopyranoside (3), methyl 4-Se-(β-D-galactopyranosyl)-2-deoxy-2-fluoro-4-seleno-β-D-glucopyranoside (4), and methyl 4-Se-(2-deoxy-2-fluoro-α/β-D-galactopyranosyl)-4-seleno-β-D-glucopyranoside (5α and 5β), the three latter compounds with an interglycosidic selenium atom. Selenoglycosides 1 and 3 were obtained from the corresponding bromo sugar by treatment with dimethyl selenide and a reducing agent, while compounds 2α/2β, 4, and 5α/5β were synthesized by the coupling of a D-galactosyl selenolate, obtained in situ from the corresponding isoselenouronium salt, with either methyl iodide or a 4-O-trifluoromethanesulfonyl D-galactosyl moiety. While benzyl ether protecting groups were found to be incompatible with the selenide linkage during deprotection, a change to acetyl esters afforded 4 in a 17% overall yield and over 9 steps from peracetylated D-galactosyl bromide. The synthesis of 5 was performed similarly, but the 2-fluoro substituent led to reduced stereoselectivity in the formation of the isoselenouronium salt (α/β ∼ 1 : 2.3). However, the β-anomer of the uronium salt could be obtained almost pure (∼98%) by precipitation from the reaction mixture. The following displacement reaction occurred without anomerisation, affording, after deacetylation, pure 5β.

中文翻译：

含氟和含硒的 D-乳糖和 D-半乳糖类似物的合成

^{由于存在19} F 和⁷⁷ Se 报告核，合成的脱氧-氟-碳水化合物衍生物和硒糖是使用核磁共振波谱研究蛋白质-碳水化合物相互作用的有用工具。合成了含有这两个原子的七种糖类，三种单糖，甲基 6-脱氧-6-氟-1-硒-β- D-吡喃半乳糖苷 ( 1 ) 和甲基 2-脱氧-2-氟-1-硒-α/ β- D -吡喃半乳糖苷（2α和2β），以及四种双糖，甲基 4- O -(β- D -吡喃半乳糖基)-2-脱氧-2-氟-1-硒代-β- D -吡喃葡萄糖苷 ( 3), methyl 4-Se-(β- D -galactopyranosyl)-2-deoxy-2-fluoro-4-seleno-β- D -glucopyranoside ( 4 ), 甲基 4-Se-(2-deoxy-2-fluoro -α/β- D -吡喃半乳糖基)-4-硒代-β- D -吡喃葡萄糖苷 ( 5α和5β )，后三种化合物具有糖苷间硒原子。硒糖苷1和3是由相应的溴代糖经二甲基硒和还原剂处理得到的，而化合物2α / 2β、4和5α / 5β是由一个D偶联合成的。-半乳糖基硒酸盐，从相应的异硒脲盐原位获得，具有碘甲烷或 4- O-三氟甲磺酰基D-半乳糖基部分。虽然发现苄基醚保护基团在脱保护过程中与硒化物键不相容，但改用乙酰酯后，从全乙酰化D-半乳糖基溴化物得到4 ，总收率为 17%，超过 9 个步骤。5的合成类似地进行，但 2-氟取代基导致异硒脲盐（α/β ~ 1：2.3）形成过程中的立体选择性降低。然而，通过从反应混合物中沉淀，可以获得几乎纯的（~98%）脲盐的 β-端基异构体。以下置换反应在没有异头化的情况下发生，在脱乙酰化后提供纯5β。

更新日期：2023-02-27

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