Multigram-Scale Synthesis of 2,5-Dideoxy-2,5-imino-d-mannitol (DMDP) and 2,5-Dideoxy-2,5-imino-d-glucitol (DGDP) from d-Fructose and l-Sorbose Using a Regioselective Appel Reaction.

Sunde-Brown, Peter; Miller, Gavin J.; Houston, Todd A.

Abstract

We report a practical 5 g scale stereoselective synthesis of the valuable iminosugar DMDP from d-fructose in only 7 synthetic steps and in a 70% overall yield, which doubles previously reported yields. This process requires only two chromatographic purification steps, taking advantage of a regioselective Appel reaction. The regioselective reaction has also been applied on a similar scale to prepare the C-2 diastereomer of DMDP, DGDP, from l-sorbose in 7 steps (two purifications) and 56% overall yield, albeit with diminished diastereomeric purity (d.r. 90:10). The C-5 regioselectivity has also been illustrated on d-psicose and d-tagatose, making this an attractive method for preparing pyrrolidine iminosugars or 5-thiosugars from ketopyranoses.

Citation

Sunde-Brown, P., Miller, G. J., & Houston, T. A. (in press). Multigram-Scale Synthesis of 2,5-Dideoxy-2,5-imino-d-mannitol (DMDP) and 2,5-Dideoxy-2,5-imino-d-glucitol (DGDP) from d-Fructose and l-Sorbose Using a Regioselective Appel Reaction. The Journal of Organic Chemistry, 90(6), 2288-2297. https://doi.org/10.1021/acs.joc.4c02667

• Journal Article Type: Article
• Acceptance Date: Jan 27, 2025
• Online Publication Date: Feb 5, 2025
• Deposit Date: Feb 28, 2025
• Publicly Available Date: Feb 28, 2025
• Journal: The Journal of organic chemistry
• Print ISSN: 0022-3263
• Electronic ISSN: 1520-6904
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 90
• Issue: 6
• Pages: 2288-2297
• DOI: https://doi.org/10.1021/acs.joc.4c02667
• Public URL: https://keele-repository.worktribe.com/output/1078326