Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• sugar nucleotides To evaluate pyrophosphorylative coupling using the C6-modified mannose 1-phosphates we selected the recombinant GDP-mannose pyrophosphorylase (GDP-Man PP) from Salmonella enterica, previously established to have a broad promiscuity for GDP-Man synthesis [4][6][15]. Glycosyl 1

• ). Conclusion We have developed a synthetic approach to a small series of C6-modified mannose 1-phosphates (6-amino, 6-chloro and 6-thio) and with these tools further explored the substrate promiscuity of the mannose pyrophosphorylase from S. enterica, observing that larger (than canonical OH) chlorine is

• : Detailed experimental protocols and characterisation data; spectral NMR data (1H, 13C and 31P NMR for compounds 10–17 and 19). Acknowledgements A clone encoding for GDP mannose-pyrophosphorylase from S. enterica was kindly donated by T. L. Lowary. Funding UK Research and Innovation (UKRI, Future Leaders

Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from Salmonella enterica

• Lu Zou,
• Ruixiang Blake Zheng and
• Todd L. Lowary

Beilstein J. Org. Chem. 2012, 8, 1219–1226, doi:10.3762/bjoc.8.136

• their ability to be converted into the corresponding guanosine diphosphate mannopyranose (GDP-Manp) analogues by a pyrophosphorylase (GDP-ManPP) from Salmonella enterica was studied. Evaluation of methoxy analogues demonstrated that GDP-ManPP is intolerant of bulky substituents at the C-2, C-3, and C-4

• synthesis; kinetics; methylation; pyrophosphorylase; sugar nucleotide; Introduction Modified sugar nucleotide analogues are valuable probes to study glycosyltransferases and other enzymes that use these activated glycosylating agents as substrates [1][2][3][4][5]. The synthesis of natural and non-natural

• attractive strategy is to employ a chemoenzymatic approach, in which a synthetic sugar 1-phosphate derivative is converted to the sugar nucleotide by a pyrophosphorylase (Figure 1B) [14][15]. This approach is increasingly used for the synthesis of sugar nucleotides, but a limitation is that the specificity

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• developing a continuous enzymatic production of GDP-mannose 43 from mannose 1-phosphate (40) using GDP-mannose pyrophosphorylase (Scheme 13), Fey and co-workers encountered a two-fold product inhibition of the enzyme by both products 43 and pyrophosphate 41, which deteriorated production performance [36

• enzyme membrane reactors. E1: GDP-mannose pyrophosphorylase; E2: Pyrophosphatase [36]. Continuous solvent-free chemo-enzymatic synthesis of ethyl (S)-3-(benzylamino)butanoate (48) in a sequence of a plug-flow reactor (PFR) and a packed-bed reactor containing Novozym 435 (E) [38]. Continuous chemo