Expedient stereoselective synthesis of glycosides: Old catalysts, new tricks

S9.3 Stereoselectivity in glycosylation reactions
Location (hall): 
Start/end time: 
Thursday, July 4, 2019 - 15:00 to 15:30
Speaker reference: 

Carmen Galan1

1School Of Chemistry, University Of Bristol, Bristol, United Kingdom

The stereoselective synthesis of glycosides remains one of the biggest challenges in carbohydrate chemistry.(1) The chemical synthesis of complex carbohydrates generally involves the coupling of a fully protected glycosyl donor bearing a leaving group at its anomeric centre, with a suitably protected glycosyl acceptor (R-OH). In many instances, these reactions lead to a mixture of two stereoisomers. 

In recent years, our group has endeavoured to develop catalytic and stereoselective methods to address this important synthetic challenge.(2-5) Recent years have seen a steady increase in the application of organocatalysis applied to oligosaccharide synthesis,(3) since the reaction conditions are mild and the careful choice of catalyst can offer significant improvements over traditional methods in terms of atom economy, high yields and control of anomeric selectivity.

Herein, we will report our latest developments on the application of  borane catalysis to oligosaccharide synthesis. We will discuss the substrate-controlled direct alpha-stereoselective synthesis of deoxyglycosides from glycal whereby 2,3-Unsaturated alpha-O-glycoside products can be obtained with deactivated glycals at 75 oC in the presence of the catalyst, while 2-deoxyglycosides are formed using activated glycals that bear no leaving group at C-3 at lower temperatures. The reaction proceeds in good to excellent yields via concomitant borane activation of glycal donor and nucleophile acceptor. The method is exemplified with the synthesis of a series of rare and biologically relevant oligosaccharide analogues.

  1. a) S. Medina and M. Carmen Galan*. Carbohydr. Chem. 2016, 41, 59–89. b) R.     Williams and M. C. Galan*  Eur. J. Org. Chem.  2017, 6247
  2. E. I. Balmond, D. M. Coe, M. C. Galan, E. M. McGarrigle. Angew. Chem. Int. Ed.            2012, 51, 9152-9155.
  3. E. I. Balmond, D. M. Coe, D. Benito-Alifonso, E. M.McGarrigle, M. C. Galan. Angew.  Chem. Int. Ed. 2014, 53, 8190-8194.
  4. a) S. Medina, M. J. Harper, E. I.           Balmond, S. Miranda, E. M. G. Crisenza, D. M. Coe, E. M. McGarrigle, M. C. Galan, Org. Lett. 2016, 18, 4222. b) C. Palo-Nieto, A. Sau, R. Williams, M. C. Galan. J. Org. Chem. 2017, 82, 407S. 
  5. a) A. Sau and M. C. Galan*. Org. Lett. 2017, 19, 2857. b) A. Sau, R. Williams, C. Palo-Nieto, A. Franconetti, S. Medina and M. C. Galan* Angew. Chem. Int. Ed. 2017, 56, 640. c) C. Palo-Nieto, A. Sau and M. C. Galan* J. Am. Chem. Soc.  2017, 139, 14041. d) Medina,  A. S. Henderson, J. F. Bower, M. C. Galan. Chem. Commun. 2015, 51, 8939-8941.