Synthesis of 4-Nitrophenyl beta-D-Galactofuranoside. A useful substrate for beta-D-Galactofuranosidases studies

POKLEPOVICH CARIDE, S.; VILLAUME S.; MARINO C.; LEDERKREMER R. M.

Carbohydrate Chemistry: Proven Synthetic Methods 4

CRC Press Taylos and Francis groupr

Año: 2017; p. 93 - 98

-D-Galactofuranosyl units (-D-Galf) are constituents of microorganisms, some of them pathogenic, such as Mycobacteria, the trypanosomatids Trypanosoma cruzi and Leishmania1 and fungi like Aspergillus fumigatus.2 Since Galf has never been found in mammals, its biosynthesis and metabolism are good targets for chemotherapeutic strategies. In some species the degradation of Galf containing glycoconjugates is promoted by extracellular -D-galactofuranosidases. For example, Penicillium and Apergillius species,3 Helminthosporium sacchari4 and Trichoderma harzianum5 produce exo -D-galactofuranosidases (EC 3.2.1.146).First studies of -D-galactofuranosidases involved the use of methyl -D-galactofuranoside as substrate and the tedious measurement of the reducing sugar released by the enzyme.4,6 The availability of the chromogenic substrate 4-nitrophenyl -D-galactofuranoside (3), first described in our laboratory7 and later reported by Cousin et al.,8 significantly simplified this task. Since then, compound 3 has been extensively used for galactofuranosidase studies in P. fellutanum,9 and Aspergillius spp.8 Compound 3 has also been used as substrate for chemoenzymatic syntheses.10,11 It used to be commercially available (Merck) but it was later discontinued. In our case, the starting compound was per-O-benzoyl--D-Galf (1),12 obtained in a single step from D-Gal, and the glycosylation was promoted by p-toluensulfonic acid.7 The other laboratory started from per-O-acetyl--D-Galf, which required three steps for its synthesis, and the glycosylating agent was SnCl4,8 which proved to be very efficient for the synthesis of different galactofuranosides.13 We describe in this chapter the synthesis of 3 by SnCl4-promoted glycosylation of easily available 1,12 followed by de-O-acylation.