Expeditious chemical synthesis of xylomannans disproves the proposed antifreeze activities

Cold-adapted species are able to generate cryoprotective proteins and glycoproteins to prevent freezing damage. The [→4)-<i>β</i>-D-Man<i>p</i>-(1→4)-<i>β</i>-D-Xyl<i>p</i>-(1→] <i>_n</i> xylomannan from the Alaska beetle <i>Upis ceramboides</i> was disclosed by Walters and co-workers in 2009 as the first glycan-based antifreeze agent, which was later reported to be found in diverse taxa. Here, we report the rapid synthesis of four types of xylomannans, including the proposed antifreeze xylomannan up to a 64-mer (Type I), the regioisomeric [→3)-<i>β</i>-D-Man<i>p</i>-(1→4)-<i>β</i>-D-Xyl<i>p</i>-(1→] <i>_n</i> 16-mer (Type II), the diastereomeric [→4)-<i>β</i>-L-Man<i>p</i>-(1→4)-<i>β</i>-D-Xyl<i>p</i>-(1→] <i>_n</i> 16-mer (Type III) and the block-wise [→4)-<i>β</i>-D-Man<i>p</i>-(1→] <i>_m</i> [→4)-<i>β</i>-D-Xyl<i>p</i>-(1→] <i>_n</i> 32-mer (Type IV), by employing a strategic iterative exponential glycan growth (IEGG) process. The nuclear magnetic resonance spectral data of the alleged natural xylomannan are in accordance only to those of the block-wise Type IV glycan and none of these synthetic xylomannans has been found to be capable of inducing thermal hysteresis. These results disprove the previous reports about the natural occurrence of antifreeze xylomannans.