Modifications of Heptulopyranosonic Acid Esters Using the Mitsunobu-Reaction

PS2 Poster session 2 Even numbers
Location (hall): 
Start/end time: 
Tuesday, July 2, 2019 - 15:45 to 17:15

Kánya Nándor1, Sándor Kun1, László Somsák1

1University Of Debrecen, Debrecen, Hungary

The Mitsunobu-reaction – which is capable of exchanging a hydroxyl-group to a protonated nucleophile – was first published in 1967 [1]. This discovery proved to be of enormous significance over the years, as a great number of articles have been published since then for the synthetic applications of the reaction [2,5,6]. The method is well-known among carbohydrate chemists as well, its first application in this field was the exchange of free hydroxyl-groups of variuos mono- and oligosaccharides to form leaving or protecting groups at different positions of the substrate [2]. However, carbohydrates that contain a tertiary hydroxyl-group are known to react slowly, if at all, due to the steric hindrance of the host carbon atom [2]. Examples for the exchange of such hydroxyl-groups are extremely scarse in the literature [3]. In order to study the spirocyclisation possibilities, we needed the substitution products of heptulopyranosonic esters, and to this end, we have studied Mitsunobu-reactions of these substrates.

Success of the Mitsunobu-reaction largely depends on the pKa value of the nucleophilic reagent [4], therefore in the first phase of our research, we attempted to react several types of N- and O-nucleophiles that have a pKa lower than ten, with the glucose derivative containing the tertiary hydroxyle-group at its anomeric centre. As a result, we have successfully managed to synthesize a few O- and N-aryl glycosides, as well as some N-glycosyl-heterocycles. Curiously, alternative ways leading to the same products (which involved the exchange of a bromine atom under regular SN conditions) have failed to provide the corresponding glycosides. Next, we examined the possibility of further transformations of these glycosides into glycosylidene-spiro-heterocycles, which may have a potential antidiabetic effect. These efforts resulted in two new spiro-compounds, but unfortunately, they showed no effect in the inhibition of glycogen-phosphorylase enzyme [7]. Finally, we attempted to use some carbohydrate derivatives, that already have an NH-acidic centre, as nucleophiles in the Mitsunobu-reaction. The detailed results of these studies will be presented on the poster.

Mitsunobu-reactions performed on heptulopyranosonic esters.

  1. O. Mitsunobu, Y. Yamada; B. Chem. Soc. Jpn., 1967, 10, 2380-2382.
  2. D. Hughes; Organic Reactions (Hoboken, NJ, United States), 1992, 42, 337-636.
  3. G. Gao, O. Schwardt, B. Ernst; Carbohydr. Res., 2004, 339, 2835-2840. 
  4. J. Hain, P. Rollin, W.Klaffke, T. K. Lindhorst; Beilstein J. Org. Chem., 2018, 14, 1619-1636.
  5. K. C. K. Swamy, N. N. B. Kumar, E. Balaraman, K. V. P. P. Kumar; Chem. Rev., 2009, 109, 2551-2651.
  6. S. Fletcher; Org. Chem. Front., 2015, 2, 739-752.
  7. Kun, S.; Kánya, N.; Galó, N.; Páhi, A.; Mándi, A.; Kurtán, T.; Makleit, P.; Veres, S.; Sipos, Á.; Docsa, T.; Somsák, L., J. Agric. Food Chem. 2019, under revision.