Synthesis of β- d-galactofuranosyl nucleoside analogues. A new type of β- d-galactofuranosidase inhibitor

• Published in: Carbohydrate research 2001-07, Vol.333 (2), p.123-128
• Main Authors: Marino, Carla, Herczegh, Pal, de Lederkremer, Rosa M
• Format: Article
• Language: English
• Subjects: 4-Imidazoline; beta-Galactosidase - antagonists & inhibitors; beta-Galactosidase - metabolism; Galactofuranosidase inhibitors; Galactosides - chemical synthesis; Galactosides - pharmacology; Humans; Imidazolidine-2-thion derivatives; Isothiocyanate; Molecular Structure; Nucleosides - chemical synthesis; Nucleosides - pharmacology; Penicillium - chemistry; Penicillium - enzymology; Thioglycosides - chemistry; Thiohydantoin
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/S0008-6215(01)00146-X

The development of β- d-galactofuranosidase inhibitors provides a good chemotherapeutic target for treatment of major human diseases, because β- d-galactofuranose is a constituent of important pathogen microorganisms but is absent in mammals. With this purpose we have prepared β- d-galactofuranosyl nucleoside analogues, derived by the addition of nucleophiles to perbenzoylated β- d-galactofuranosyl isothiocyanate, a compound previously prepared in this laboratory. N-β- d-Galactofuranosyl- O-ethylthiourethane, N-β- d-galactofuranosyl-4-oxoimidazolidine-2-thione, N-β- d-galactofuranosyl-4-imidazoline-2-thione, and N-β- d-galactofuranosyl-4-methoxyimidazolidine-2-thione, were prepared. The biological assays showed that imidazoline and imidazolidine-2-thione derivatives act as a new type of exo β- d-galactofuranosidase inhibitor. Graphic