Collect. Czech. Chem. Commun.
2005, 70, 519-538
https://doi.org/10.1135/cccc20050519
Synthesis of Novel Conformationally Locked Carbocyclic Nucleosides Derived from 5,5- and 6,6-Bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol
Hubert Hřebabecký*, Milena Masojídková and Antonín Holý
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
Abstract
(1R*,2R*,3R*,4S*)-3-Amino-6,6-bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol (13) was prepared from (bicyclo[2.2.1]hept-5-ene-2,2-diyl)dimethyl dibenzoate (7) via cis-diol 8, cyclic sulfate 10, and azide 12. (1R*,2R*,3S*,4S*)-3-Amino-6,6-bis(hydroxymethyl)bicyclo[2.2.1]-heptan-2-ol (18) and (1R*,2S*,3S*,4S*)-3-amino-5,5-bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol (19) were obtained by addition of chromyl azide to double bond of 7, chromatographic separation, debenzoylation and hydrogenation of resulting azides 14 and 16. The amines 13, 18, and 19 were used to build (1R*,2R*,3R*,4S*)- (21a), (1R*,2R*,3S*,4S*)-3-(6-chloro-9H-purin-9-yl)-6,6-bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol (21b), and (1R*,2S*,3S*,4S*)-3-(6-chloro-9H-purin-9-yl)-5,5-bis(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol (21c), respectively. Ammonolysis of these compounds led to 6-amino-9H-purine derivatives 22a-22c. 6-(Dimethylamino)-9H-purine analogues 23a-23c and 6-(cyclopropylamino)-9H-purine analogues 24a-24c were prepared by aminolysis of 21a-21c. Reaction of amines 13, 18, and 19 with ethyl N-((2E)-3-ethoxymethacryloyl)carbamate afforded thymine derivatives 28a-28c.
Keywords: Azides; Amines; Cyclic sulfates; Nucleosides; Carbocyclic nucleosides; Purines; Pyrimidines; Nucleobases; Alkenes; Azidohydroxylation; Antivirals.
References: 26 live references.
