The first general synthesis of 2-C-(β-d-glycopyranosyl)pyrimidines and their evaluation as inhibitors of some glycoenzymesElectronic supplementary information (ESI) available: Further details of the experimental procedures and compound characterization. See DOI: 10.1039/c8nj04035d

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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Main Authors: Szennyes, Eszter, Bokor, Éva, Langer, Peter, Gyémánt, Gyöngyi, Docsa, Tibor, Sipos, Ádám, Somsák, László
Format: Article
Language:English
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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. The first systematic study on the synthesis of 2- C -(β- d -glycopyranosyl)pyrimidines either from amidine A or glycosyl cyanides B and 1,3-dicarbonyl compounds.
ISSN:1144-0546
1369-9261
DOI:10.1039/c8nj04035d