Glycal-Type Enecarbamates: Straightforward Access to O- and S-Alpha-Glycoside Mimetics

PS1 Poster session 1 Odd numbers
Location (hall): 
Start/end time: 
Monday, July 1, 2019 - 15:45 to 17:15

Elena M. Sánchez-Fernández1, Irene Herrera1, Cristina Nativi2, Abhijit Sau3, Carmen Galán3, José M García Fernández4, Carmen Ortiz Mellet1

1University of Seville, Seville, Spain, 2University of Florence, Florence, Italy, 3University of Bristol, Bristol, United Kingdom, 4Instituto de Investigaciones Químicas, CSIC – University of Seville, Seville, Spain

Chemically and configurationally stable sp²-iminosugar N-, S-, O- and C- pseudo-α-glycosides have shown interesting biological properties as anti-tumor, anti-parasitic and anti-inflammatory agents [1]. The high α-anomeric selectivity achieved in the corresponding glycosylation reactions, using glycosyl fluoride or peracetylated donors, in this family of glycomimetics, is attributed to the presence of the endocyclic sp²-hybridised nitrogen, which results in an unusually strong orbital contribution to the generalized anomeric effect [2]. This peculiar reactivity has further been exploited in the preparation of Tn antigen (GalNAc-α-O-Ser/Thr) mimics as precursors of anti-cancer vaccines [3]. In this case, the incorporation of the acetamido group involved the unsaturated derivative 3a (Figure 1), which can be considered a glycal-enecarbamate hybrid. Given that glycals and enecarbamates have a quite reach chemistry, the use of synthetic intermediates combining the structural features of both classes of compounds to access new families of glycomimetics is very appealing. As a showcase, here we present the efficient synthesis of 2-deoxy-α-glycoside mimics, keeping in mind that this structural unit is present in a wide variety of biologically active natural products [4]. A range of alcohols/thiols have been used as glycosyl acceptors against the pseudoglycals 3a-3c, using different promotors to trigger activation of the C=C bond (boron trifluoride-diethyl ether, ceric ammonium nitrate or thiourea-type organocatalysts). The scope and limitations of the methodology will be discussed.

Figure 1. Retrosynthetic scheme for the stereoselective synthesis of 2-deoxy-α-O-(S)-glycomimetics.

  1. a) E.M. Sánchez-Fernández et al., Chem. Commun. 2010, 46, 5328-5330; b) E.M. Sánchez-Fernández et al., RSC Adv. 2015, 5, 21812-21822; c) E. Schaeffer et al., Eur. J. Med. Chem. 2019, 169, 111-120.
  2. V.M. Díaz Pérez et al., J. Org. Chem. 2000, 65,136-143.
  3. E.M. Sánchez-Fernández et al, Org. Lett. 2016, 18, 3890-3893.
  4. C.S. Bennett et al., Chem. Rev., 2018, 118, 7931-7985.