Novel O- and N-Linked Inositol Oligomers: A New Class of Unnatural Saccharide Mimics

Abstract

Several N- as well as O-linked inositol oligomers were synthesized by a chemo-enzymatic approach. Whole-cell fermentation of bromobenzene with E. coli JM109(pDTG601) furnished a chiral cis-dienediol which was converted into its vinyl epoxide and vinyl aziridine, respectively. Two-fold epoxide/aziridine openings catalyzed by Yb(OTf)₃ served as the key step in the synthesis of N-linked analogs, whereas a convergent approach furnished the O-linked inositol oligomers. Their synthesis is described and structural comparisons drawn to higher oligomers of l-chiro- and neo-inositol oligomers.

Key words

oligosaccharides - ring-opening - epoxides - aziridines - inositols

References

• 1 Gabius H.-J. Naturwissenschaften  2000,  87:  108 
• 2 Sears P. Wong C.-H. Angew. Chem., Int. Ed.  1999,  38:  2300 
• 3 Hudlicky T. Abboud KA. Entwistle DA. Fan R. Maurya R. Thorpe AJ. Bolonick J. Myers B. Synthesis  1996,  897 
• 4 vanAlmsick M. Dolhaine H. Hönig H. MATCH  1999,  39:  21 
• 5 Hudlicky T. Abboud KA. Bolonick J. Maurya R. Stanton ML. Thorpe AJ. J. Chem. Soc., Chem. Commun.  1996,  1717 
• For synthesis and evaluation of antiglycosidic properties of similar compounds see:
• 6a Desjardins M. Lallemand M.-C. Freeman S. Hudlicky T. Abboud KA. J. Chem. Soc., Perkin Trans. 1  1999,  621 
• 6b Desjardins M. Lallemand M.-C. Hudlicky T. Abboud KA. Synlett  1997,  728 
• 7a Gibson DT. Hensley M. Yoshioka H. Mabry TJ. Biochemistry  1970,  9:  1626 
• 7b Hudlicky T. Luna H. Barbieri GL. Kwart LD. J. Am. Chem. Soc.  1988,  110:  4735 
• 7c Hudlicky T. Stabile MR. Gibson DT. Whited GM. Org. Syn.  1999,  76:  77 
• 8 Hudlicky T. Tian XR. Königsberger K. Rouden J. J. Org. Chem.  1994,  59:  4037 
• 9a Tian XR. Hudlicky T. Königsberger K. J. Am. Chem. Soc.  1995,  117:  3643 
• 9b Hudlicky T. Tian XR. Königsberger K. Maurya R. Rouden J. Fan B. J. Am. Chem. Soc.  1996,  118:  10752 
• 10 Hudlicky T. Luna H. Olivo H. Andersen C. Nugent T. Price JD. J. Chem. Soc., Perkin Trans. 1  1991,  2907 
• 13 Restrepo-Sanchez N. PhD dissertation   University of Cali; Columbia: 2001. work performed at the University of Florida

11

The ratio of 18a:18b seems to vary considerably with the reaction scale. Although we have separated 18a and 18b to establish their regiochemistry, it is not necessary to do so for preparative runs, since both ultimately yield 20.

12

These results will be reported in an upcoming full paper.

14

All molecular modeling was performed with SPARTAN SGI version 5.1.1, available from Wavefunction Inc., on a Silicon Graphics O².