LaCl3-Enabled Synthesis of 2'-C-Substituted Galidesivir Analogues
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Updated: Oct 31, 2026

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products
Published on: September 9, 2016
James M Wood1,2, Rinu Shrestha1,2, Ashley Nutsford3
1Ferrier Research Institute, Te Herenga Waka─Victoria University of Wellington, Wellington6012, New Zealand.
Abstract:
The first synthesis of 2'-C-ethynylgalidesivir is reported. Access to this highly congested imino-C-nucleoside required development of a LaCl3·2LiCl-enabled addition of a 9-deazaadenine-derived Grignard reagent to 2'-C-substituted cyclic nitrones. The reaction proceeds with high β selectivity and enables the synthesis of galidesivir, 2'-C-methylgalidesivir, and 2'-C-ethynylgalidesivir. The respective syntheses required 6, 11, and 11 steps from known intermediates and proceeded in 54%, 22% and 17% overall yield. NMR titration and order-of-addition studies suggested that LaCl3·2LiCl perturbs both the nitrone substrate and Grignard speciation. Antiviral evaluation of the ethynyl analogue and its phosphoramidate prodrug revealed only weak activity at high concentration.
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