Recent studies have shown that L-like carbocyclic nucleosides, such as L-isoneplanocin analogues, possess broad spectrum antiviral activities, including Ebola, norovirus, vaccinia, HBV, HCMV, measles and Dengue. It is noteworthy that replacing the nitrogen atom to a CH or a CBr group at the N-3 position has significant impacts on their biological properties. Previous studies have also found that C-4’ truncated neplanocin analogue (DHCDA) is effective against a series of viruses, which is likely due to its inhibition of SAH hydrolase. Its selectivity was even greater than that of neplanocin, particularly against vesicular stomatitis virus (VSV) and rotavirus. Following the lead of these compounds and as part of a program that is study L-like carbocyclic nucleosides, the L form of DHCDA (1), its 3-Br derivative (3), and the conformation restricted methanocarba (MC) nucleoside analogues (2 and 4) were set as target structures. The L form MC nucleoside analogues (2, 4) have similar locked conformation as conventional D-MC nucleosides, but different configuration, which will provide interesting information regarding to their antiviral activities. The L-5’-isoneplanocin (5) and its 3-deaza analogue (6) targets were also included in the study of L-like carbocyclic nucleosides. The synthesis of these compounds and their antiviral properties will be described.

Design and synthesis of L-neplanocin analogues as antiviral agents

253rd National Meeting (2017)

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