DOI: 10.1021/acs.orglett.6c02533 ISSN: 1523-7060
2-Naphthylmethyl Protecting Group Strategy for Streamlined Synthesis of a Fondaparinux Analogue
Zhenghao Wu, Xiao Liu, Deqian Li, Lin Yan, Min Li, Xiongyan Meng, Huiting Li, Shiyan Mai, Shuai Meng, Tiantian Sun, Chengli ZongAbstract
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.