4-表异麦角胺的5-氟衍生物作为D-半乳糖苷酶抑制剂以及用于GM1神经节苷脂贮积症和法布里病的潜在药理伴侣。
5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease.
作者信息
Thonhofer Martin, Gonzalez Santana Andres, Fischer Roland, Torvisco Gomez Ana, Saf Robert, Schalli Michael, Stütz Arnold E, Withers Stephen G
机构信息
Glycogroup, Institute for Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
出版信息
Carbohydr Res. 2016 Feb;420:6-12. doi: 10.1016/j.carres.2015.10.009. Epub 2015 Dec 8.
Electrophilic fluorination of an exocyclic methoxymethylene enol ether derived from N-tert-butyloxycarbonyl-1,5-dideoxy-1,5-imino-3,4-O-isopropylidene-D-erythro-pent-2-ulose (11) provided the 5-fluoro derivative of the powerful β-galactosidase inhibitor 4-epi-isofagomine (8). This structural alteration, in combination with N-alkylation, led to considerably improved α-galactosidase selectivity. New compounds may serve as leads en route to new pharmacological chaperones for Fabry's disease.
对源自N-叔丁氧羰基-1,5-二脱氧-1,5-亚氨基-3,4-O-异亚丙基-D-赤藓糖-2-酮（11）的环外甲氧基亚甲基烯醇醚进行亲电氟化反应，得到了强效β-半乳糖苷酶抑制剂4-表异法戈明（8）的5-氟衍生物。这种结构改变与N-烷基化相结合，使得α-半乳糖苷酶选择性得到显著提高。新化合物有望成为通往法布里病新型药理伴侣的先导化合物。
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