Multicomponent Approach to Homo- and Hetero-Multivalent Glycomimetics Bearing Rare Monosaccharides

Abstract

We applied a multicomponent approach to access a library of densely functionalized homo- and hetero-multivalent glycomimetics comprising aldehyde, amine, and isocyanide components related to isopropylidene-protected d-fructose, l-sorbose, d-galactose, and d-allose. Passerini products were obtained in very good yields (up to 78%) and high diastereoselectivities (up to 98:2). Three types of products were obtained by the Ugi reaction; along with the “classical” four-component product, α-acylaminoamides, a three-component α-aminoamides, and a four- component α-aminoacylamides were isolated. The presence of multiple pathways is rationalized by the structure of the imidate intermediate, mainly influenced by the amine component.

The synthesis of oligomers containing alternating C-glycosyl α-amino acids and proteinogenic α-amino acids

“…(3aR,5S,5aR,8aS,8bR)-2,2,7,7-tetramethyltetra-hydro-5H-bis([1,3]dioxolo)[4,5-b:4 0 ,5 0 -d]pyran-5-carbaldehyde (Gal-related aldehyde) and (3aS,3bR,7aS,8aR)-2,2,5,5-tetramethyltetrahydro-8aH- [1,3]dioxolo[4 0 ,5 0 :4,5]furo[3,2-d][1,3]dioxine-8a-carbaldehyde (Sor-related aldehyde) were prepared following published procedure. 21 General procedure for the synthesis of amino acid-derived isocyanides Amino acid methyl ester (1 equiv.) was dissolved in DCM and solution was cooled to 0 1C.…”

“…(3 aR ,5 S ,5 aR ,8 aS ,8 bR )-2,2,7,7-tetramethyltetra-hydro-5 H -bis([1,3]dioxolo)[4,5- b :4′,5′- d ]pyran-5-carbaldehyde (Gal-related aldehyde) and (3 aS ,3 bR ,7 aS ,8 aR )-2,2,5,5-tetramethyltetrahydro-8aH-[1,3]dioxolo[4′,5′:4,5]furo[3,2- d ][1,3]dioxine-8 a -carbaldehyde (Sor-related aldehyde) were prepared following published procedure. 21…”

Sugars in Multicomponent Reactions: A Toolbox for Diversity-Oriented Synthesis

“…The Jeric group 35 have also synthesized a varied range of substituted homo- and hetero-multivalent glycomimetics 46 , 47 , 48 , and 49 via the three-component Passerini and three- and four-component Ugi reactions of appropriate aldehydes 42 , isocyanides 43 , carboxylic acids 44 , and amines 45 derived from isopropylidene-protected d -fructose, d -galactose, d -allose, and l -sorbose (Scheme 8 ). The three-component Passerini reaction was conducted with various aldehydes 42 , isocyanides 43 , and carboxylic acid 44 derivatives.…”

The 100 facets of the Passerini reaction

“…The same protocol was later applied to the reaction involving other sugar aldehydes (from sorbose, galactose, and allose), and sugar isocyanides and carboxylic acids: the robustness of the methodology was demonstrated and in some cases d.r.s are >99%, while the yields depend on the nature of the reagents. 95 …”