First Jump to Gram-Scale Heparin Dodecassaharide Synthesis - route to new scales and sequences

Dr John Gardiner's group's paper, "First Gram-scale Synthesis of a Heparin-related Dodecasaccharide" has been the subject of a Highlight news article in Chemical & Engineering News.

Gram-scale Synthesis of a Heparin-related Dodecasaccharide

Dr John Gardiner's group's paper, "First Gram-scale Synthesis of a Heparin-related Dodecasaccharide" has been the subject of a Highlight news article in Chemical & Engineering News.

Synthetic access to long, complex heparanoid-type oligosaccharides is at the forefront of current chemical glycobiology, with pursuit of effective methods to provide structurally-modified pure long oligosaccharides, critical tools to begin unravelling the chemical biology of these structures, and to evaluate their in vivo effects. Until recently, only tens of mgs of deca- and dodecasaccharides (10-mers and 12-mers) had been accessible from the pioneering synthetic work of several international labs, with the race on to provide demonstration of synthetic routes sufficiently efficient to provide larger gram-pscale amounts. Sufficiently scalable access to the rare iduronate component of the most important targets has been a limitation. In, 2012 synthetic work by postdocs Steen Hansen and Gavin Miller (John Gardiner group), funded by an MRC DFPS Project Grant, has been published providing the first large-scale access to the key iduronate-containing building blocks (J. Org. Chem., 2012, 77, pp 7823–7843), and reporting the first gram-scale synthesis of any heparin dodecasaccharide (Org. Lett., DOI: 10.1021/jo300722y). This significant jump in scale capability, in a synthesis only 14 steps from multigram batches of the building block disaccharide, has been highlighted in the final 2012 issue of Chemical & Engineering News ('Heparin Building Blocks Go Upscale'). This research opens the way to addressing access to a wider diversity of structures and lengths more readily that has yet been possible on scales suitable for a wide range of investigations.

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