Anti-metastatic semi-synthetic sulfated maltotriose C-C linked dimers. Synthesis and characterisation

Abstract

This manuscript describes the preparation and the spectroscopic characterisation of semi-synthetic sulfated maltotriose C-C linked dimers (SMTCs) where the natural C-O-C anomeric bond was substituted by one direct central C-C bond. This C-C bond induces conformation and flexibility changes with respect to the usual anomeric bond. SMTCs neutral precursors came from maltotriosyl bromide electroreduction through maltotriosyl radical intermediate dimerisation. The new C-C bond configuration, named for convenience α,α, α,β and β,β as the natural anomeric bond, dictated the statistic ratio formation of three diastereoisomers. They were separated by silica gel flash chromatography followed by semi preparative HPLC chromatography. Each diastereoisomer was exhaustively sulfated to afford the corresponding SMTCs. SMTCs were huge characterised by NMR spectroscopy which provided the sulfation degree, too. α,α and α,β were found quite homogeneous samples with a high degree of sulfation (85-95%). β,β appeared a non-homogeneous sample whose average sulfation degree was evaluated at around 78%. Mass spectroscopy experiments confirmed the sulfation degree range. Some considerations were proposed about SMTCs structure-biological properties.

Figure 1

Structures of the maltotriose and maltose C-C linked dimers 1–3 and 7,8 and of their sulfated forms (SMTCs) 4–6 and 9,10.

Scheme 1

Summary of 4–6 and 9,10 preparation from commercially available maltotriose and maltose.

Figure 2

Comparison of ¹H-NMR spectra of 6 (blue) at T = 303 K and its hydroxyl precursor 3 (red) at 298 K. 500 MHz in D₂O.

Figure 3

1D ¹H-NMR (red) and ¹H-¹³C DEPT-HSQC NMR spectra (positive phase (blue) and negative phase (green), respectively secondary and primary carbons) of 6.

Figure 4

Comparison of ¹H-NMR regions of anomeric protons of 5, after one (green), two (red) and three (blue) sulfation reactions.

Figure 5

LC-MS analyses of α,β 6, α,α 4 and β,β 5 compounds. Labels indicate the number of sulfate groups for detected species.

Figure 6

HPLC chromatogram of acetylated maltotriose dimers mixture.