(1RS,2RS,6RS)-2-(6-Amino-9H-purin-9-yl)-8-azaspiro[5.6]dodec-10-en-1-ol Dihydrochloride

Abstract

The title compound (1RS,2RS,6RS)-2-(6-Amino-9H-purin-9-yl)-8-azaspiro[5.6]dodec-10-en-1-ol dihydrochloride was synthesized for the first time in two steps, the first of which was a regioselectivity of epoxide ring-opening reaction under the action of adenine, yielding N-tert-butoxycarbonyl-((1RS,2RS,6RS)-2-(6-amino-9H-purin-9-yl)-8-azaspiro[5.6]dodec-10-en-1-ol. By treating the latter with a saturated methanolic solution of hydrogen chloride, it was possible to obtain ((1RS,2RS,6RS)-2-(6-Amino-9H-purin-9-yl)-8-azaspiro[5.6]dodec-10-en-1-ol dihydrochloride. The features of the molecular and crystal structure of ((1RS,2RS,6RS)-2-(6-Amino-9H-purin-9-yl)-8-azaspiro[5.6]dodec-10-en-1-ol dihydrochloride are discussed based on X-ray diffraction studies. The product overall yield was 40% out of two steps and after purification by column chromatography and recrystallization. The product was characterized by 1H-NMR, 13C-NMR, IR spectroscopy, HRMS and X-ray.

Synthesis of Substituted Pyrrole Derivatives Based on 8-Azaspiro[5.6]dodec-10-ene Scaffold

“…Amine hydrochloride 4 was obtained by removing the protecting group under acidic conditions. The stereochemistry of such compounds was assigned through comparison with similar structures from the literature [19]. Then, compounds 5-10 were synthesized from amine hydrochloride 4 using a coupling reaction.…”

Phenotypic assessment of antiviral activity for spiro‐annulated oxepanes and azepenes

“…We have performed a phenotypic screening of antiviral activity spectrum of fragment‐sized (MW ~ 350 Da) small molecules from spiro‐annulated oxepane and azepene series (Iusupov & Kurkin, 2024; Iusupov, Lukyanenko, et al., 2022; Iusupov, Lyssenko, et al., 2022) in cell‐based assays against several diverse viruses causing human infectious diseases. Antiviral activity was never studied before for these or similar compounds.…”

“…Synthesis of these structures usually relies on the mechanisms involving the ring expansion of either five or six‐membered compounds using various methods, for example thermally, photochemically, or by microwave irradiation. In our earlier works a linear sequence of transformations was developed (Iusupov & Kurkin, 2024; Iusupov, Lukyanenko, et al., 2022; Iusupov, Lyssenko, et al., 2022) based on the use of commercially available reagents, which allows to control the process and obtain either spiro‐oxepine or spiro‐oxepane derivatives. The uniqueness of this chemical transformation is that new spiro derivatives of seven‐membered heterocycles with one heteroatom can be obtained in high yield and then can be easily transformed through trivial chemical transformations into further spiro‐analogs needed for the structure–activity relationship exploration.…”