A new, scalable preparation of a glucopyranosylidene-spiro-thiohydantoin: one of the best inhibitors of glycogen phosphorylases
2000; Elsevier BV; Volume: 11; Issue: 8 Linguagem: Inglês
10.1016/s0957-4166(00)00107-5
ISSN1362-511X
Autores Tópico(s)Glycogen Storage Diseases and Myoclonus
ResumoBenzobromo-glucose was converted into per-O-benzoylated β-d-glucopyranosyl cyanide by mercury(II) cyanide in nitromethane. Partial hydrolysis of the nitrile with hydrogen bromide in acetic acid gave per-O-benzoylated C-(β-d-glucopyranosyl)formamide. Photobromination using bromine in carbon tetrachloride, chloroform, or dichloromethane gave the corresponding per-O-benzoylated 1-bromo-1-deoxy-β-d-glucopyranosyl cyanide and C-(1-bromo-1-deoxy-β-d-glucopyranosyl)formamide. Reaction of the latter with ammonium thiocyanate in nitromethane gave the per-O-benzoylated C-6S configured glucopyranosylidene-spiro-thiohydantoin together with a small amount of the per-O-benzoylated C-(1-hydroxy-β-d-glucopyranosyl)formamide. Debenzoylation of the spiro-thiohydantoin with sodium methoxide in methanol gave gram amounts of the title inhibitor. The described sequence should be suitable for scaling up and the target compound can be prepared in ∼30% overall yield starting from d-glucose.
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