Sugar γ‐Amino Acids as Building Blocks for the Synthesis of Cyclic Neoglycopeptides.

Abstract

Anomeric sugar γ‐amino acids efficiently obtained by nucleophilic addition of nitronate anion on sugar olefins are useful building blocks for the preparation of new cyclic glycopeptides. Cyclopeptides have interesting biological properties or find potential applications as templates for anchoring of a wide range of biomolecules or detection dyes. We report here the synthesis of two types of cyclic systems containing γ‐glyco amino acid and α‐amino acid units. A first example was prepared to demonstrate the feasibility of the cyclization of these original structures. To explore the feasibility with more functionalized structures, α‐amino acid and sugar amino‐acid moieties bearing additional functions were chosen as building blocks for the second macrocycle. Furthermore, we describe and explain some unexpected results obtained during deprotection of these new cyclic glycopeptides.

Synthesis of anti-proliferative [3.3.0]furofuranone derivatives by lactonization and functionalization of C-glycosyl compounds

“…Indeed, we previouly described a spontaneous concommitant acetal deprotection and lactonization during acid catalyzed removal of isopropylidene leading to a C-glycosyl bicyclic lactone in which the lactone ring is annulated to a furanoid system. [13] Among the numerous synthetic methods to prepare C-glycosyl derivatives, we developped and used for several years the double bond reduction of C-glycosylidene compounds commonly called exoglycals (compound 2). Thus, starting from commercially available D-ribonolactone 1 (Scheme 1) and D-gulonolactone 18 (Scheme 4), we managed to prepare C-5 and C-5/C-6 stereoisomers of the bicyclic furofuranone moiety of (+)-Gogniofufurone respectively.…”

“…[1][2][3][4] In this context, our lab was early involved in the development of C-glycosidic derivatives [5][6][7][8] to build bioactive compounds, [9,10] peptidomimetic derivatives [11] suitable for imaging applications [12] and also for the design and synthesis of foldamers. [13,14] In the course of the synthesis of glycopeptides based on sugar γ-amino acids, we reported the spontaneous formation of a C-glycosyl bicyclic lactone in which the lactone ring is annulated to a furanoid system. [13] The [3.3.0]furofuranone scaffold obtained this way is found in numerous families of biologically active natural and synthetic products explaining the continual interest nowadays in its chemistry.…”

“…[13,14] In the course of the synthesis of glycopeptides based on sugar γ-amino acids, we reported the spontaneous formation of a C-glycosyl bicyclic lactone in which the lactone ring is annulated to a furanoid system. [13] The [3.3.0]furofuranone scaffold obtained this way is found in numerous families of biologically active natural and synthetic products explaining the continual interest nowadays in its chemistry. [15][16][17][18][19] Figure 1a shows some natural molecules with [3.3.0]furofuranone structure.…”

“…Optical rotations were measured on an Anton-Paar MCP 300 polarimeter 1. H and13 C NMR spectra were recorded on a Bruker Avance III 400 (400 MHz and 100.6 MHz, respectively). For complete assignment of 1 H and13 C signals, two-dimensional 1 H, 1 H COSY and 1 H,13 C correlation spectra were recorded.…”

“…H and13 C NMR spectra were recorded on a Bruker Avance III 400 (400 MHz and 100.6 MHz, respectively). For complete assignment of 1 H and13 C signals, two-dimensional 1 H, 1 H COSY and 1 H,13 C correlation spectra were recorded. Chemical shifts (δ) are given in parts per million relatives to the solvent residual peak.…”