Intramolecular Tandem seleno-Michael/Aldol Reaction - Novel Strategy in Carbasugars Synthesis

Carbasugars are a wide group of carbohydrate mimetics in which the ring oxygen had been replaced by a methylene group.¹ The high importance of these compounds is related to their interesting biological and pharmacological properties which are the matter of current studies.

In our work, concise synthesis of carbasugars from naturally occurring D-pentoses is presented. The one-pot seleno-Michael reaction connected with intramolecular aldol reaction is a key step of the carbasugar core asymmetric synthesis. Further transformation of obtained carbasugar moiety led to different bioactive compounds.^{2, 3}

Tandem seleno-Michael reaction conjugated with oxidation/elimination step of in situ generated nucleophile has been described a few years ago in the intermolecular variant.⁴ In our work, we present the first example of this reaction in an intramolecular way which leads to a previously inaccessible cyclic product of Morita-Baylis-Hillman reaction. Conducted experiments allowed to receive cyclic products with high yields and good diastereoisomeric excesses.⁵

Further research on the developed method allows applying trimethylsilyl ethers as temporary protecting groups. This protocol drastically decreased synthesis time and resulted in total yields up to 40% from naturally occurring pentoses.

This work was financed by the Polish National Science Center (Grant No. 2015/17/D/ST5/01334 & 2018/31/N/ST5/03503)

[1] O. Arjona, A. M. Gómez, J. C. López, J. Plumet, Chem. Rev., 2007, 107, 1919.

[2] N. Biduś; P. Banachowicz; S. Buda, Tetrahedron, 2020, doi.org/10.1016/j.tet.2020.131397.

[3] P. Banachowicz; S. Buda, RSC Adv., 2019, 9, 12928.

[4] B. A. Sousa, A. A. Dos Santos, Eur. J. Org. Chem., 2012, 18, 3431.

[5] P. Banachowicz; J. Mlynarski; S. Buda, J. Org. Chem., 2018, 83, 11269.