An Improved Synthetic Route to the Potent Angiogenesis Inhibitor Benzyl Manα(1→3)-Manα(1→3)-Manα(1→3)-Manα(1→2)-Man Hexadecasulfate*

Ligong Liu; Ken D. Johnstone; Jon K. Fairweather; Keith Dredge; Vito Ferro

doi:10.1071/CH09015

RESEARCH FRONT

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An Improved Synthetic Route to the Potent Angiogenesis Inhibitor Benzyl Manα(1→3)-Manα(1→3)-Manα(1→3)-Manα(1→2)-Man Hexadecasulfate*

Ligong Liu ^A ^B , Ken D. Johnstone ^A , Jon K. Fairweather ^A ^C , Keith Dredge ^A and Vito Ferro ^A ^D ^E

+ Author Affiliations

- Author Affiliations

^A Drug Design Group, Progen Pharmaceuticals Limited, Darra, Qld 4076, Australia.

^B Current address: Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia.

^C Current address: Chemical Analysis Pty Ltd, 41 Greenaway Street, Bulleen, Vic. 3105, Australia.

^D Current address: CRC for Polymers, School of Physical and Chemical Sciences, Queensland University of Technology, GPO Box 2434, Brisbane, Qld 4001, Australia.

^E Corresponding author. Email: vito.ferro@qut.edu.au

Australian Journal of Chemistry 62(6) 546-552 https://doi.org/10.1071/CH09015
Submitted: 8 January 2009 Accepted: 5 February 2009 Published: 10 June 2009

Abstract

An improved synthetic route to α(1→3)/α(1→2)-linked mannooligosaccharides has been developed and applied to a more efficient preparation of the potent anti-angiogenic sulfated pentasaccharide, benzyl Manα(1→3)-Manα(1→3)-Manα(1→3)-Manα(1→2)-Man hexadecasulfate, using only two monosaccharide building blocks. Of particular note are improvements in the preparation of both building blocks and a simpler, final deprotection strategy. The route also provides common intermediates for the introduction of aglycones other than benzyl, either at the building block stage or after oligosaccharide assembly. The anti-angiogenic activity of the synthesized target compound was confirmed via the rat aortic assay.

^* Dedicated to Professor Bob Stick on the occasion of his retirement.

Acknowledgements

The authors thank Drs Richard Furneaux, Derek Watt, and Colin Hayman (Glycosyn, NZ) for useful discussions and suggestions. Ms Kat Davis is gratefully acknowledged for technical assistance with the rat aortic assay.

References

An Improved Synthetic Route to the Potent Angiogenesis Inhibitor Benzyl Manα(1→3)-Manα(1→3)-Manα(1→3)-Manα(1→2)-Man Hexadecasulfate*

Abstract

Acknowledgements

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