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A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products
Published on: September 9, 2016
2-Naphthylmethyl Protecting Group Strategy for Streamlined Synthesis of a Fondaparinux Analogue
Zhenghao Wu1, Xiao Liu1, Deqian Li1
1School of Pharmaceutical Sciences, Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou570288, China.
Abstract:
Fondaparinux synthesis remains challenging because of demanding stereochemical control, protecting group manipulation, and purification of highly functionalized intermediates. We report a 2-naphthylmethyl (Nap) protecting group strategy for an azide-functionalized fondaparinux analogue. Direct C-2 Nap installation, combined with C-6 2-(diphenylphosphinoyl)acetyl (DPPA)-assisted β-glucosylation, streamlined assembly, while Nap-mediated phase behavior enabled 17 of 20 intermediates to be isolated without chromatography. The final analogue showed anti-FXa activity comparable to commercial fondaparinux.
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