Regio- and Stereoselective Synthesis of C-4' Spirocyclobutyl Ribofuranose Scaffolds and Their Use as Biologically Active Nucleoside Analogues.
Org Lett
; 23(22): 8828-8833, 2021 11 19.
Article
em En
| MEDLINE
| ID: mdl-34730365
ABSTRACT
Novel C-4',C-5' cyclobutane-fused spirocyclic ribonucleoside analogues were prepared. Thermal [2 + 2] cycloaddition between dichloroketene and readily derived 4'-exo-methylene furanoses afforded a first entry to the required constrained ribofuranoses, relying on a carbonyl transposition sequence. Alternatively, an unusual stereoselective ionic [2 + 2] cycloaddition using methyl propiolate promoted by methylaluminoxane gave a complementary, more direct approach to such ribofuranoses. Further conversion to the constrained adenosine analogues revealed promising structure-dependent inhibition of the protein methyltransferase PRMT5MEP50 complex in the (sub)micromolar range.
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Base de dados:
MEDLINE
Assunto principal:
Adenosina
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article