The first general synthesis of 2- C -(β- d -glycopyranosyl)pyrimidines and their evaluation as inhibitors of some glycoenzymes

A systematic study was performed on the preparation of unknown 2- C -(β- d -glucopyranosyl)pyrimidines. Pinner type cyclisation of O -perbenzylated C -(β- d -glucopyranosyl)formamidine with β-ketoesters, dimethyl malonate, and β-diketone derived α,β-unsaturated β-chloroketones followed by catalytic...

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Bibliographic Details
Published in:New journal of chemistry 2018, Vol.42 (21), p.17439-17446
Main Authors: Szennyes, Eszter, Bokor, Éva, Langer, Peter, Gyémánt, Gyöngyi, Docsa, Tibor, Sipos, Ádám, Somsák, László
Format: Article
Language:English
Subjects:
Catalysis
Cyanides
Galactosidase
Glucosidase
Pyrimidines
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Summary:A systematic study was performed on the preparation of unknown 2- C -(β- d -glucopyranosyl)pyrimidines. Pinner type cyclisation of O -perbenzylated C -(β- d -glucopyranosyl)formamidine with β-ketoesters, dimethyl malonate, and β-diketone derived α,β-unsaturated β-chloroketones followed by catalytic hydrogenation resulted in various substituted 2- C -(β- d -glucopyranosyl)-pyrimidin-4(3 H )-ones, and 2- C -(β- d -glucopyranosyl)-4,6-disubstituted-pyrimidines, respectively, in moderate to good yields. The above pyrimidine derivatives were also obtained by ring closure of the unprotected C -(β- d -glucopyranosyl)formamidine with the same 1,3-dielectrophiles. In addition, a continuous one-pot three-step procedure starting from O -peracylated d -glycopyranosyl cyanides was also elaborated to give representatives of the aforementioned pyrimidines with various sugar configurations in acceptable to excellent overall yields (25–94%). Due to the versatility of the applied 1,3-dielectrophiles, these synthetic routes represent the first expansible method to obtain the target compounds. The new C -glycopyranosyl pyrimidines showed moderate inhibition against α-glucosidase and β-galactosidase enzymes, had, however, no activity against glycogen phosphorylase. The obtained molecule library is ready for further biological testing.
ISSN:1144-0546
1369-9261
DOI:10.1039/C8NJ04035D