An efficient synthesis of novel l-rhamnose based non-ionic surfactants under controlled microwave irradiation

The scope and limitations of microwave-assisted glycosylation for the preparation of various alkyl l-rhamnoside amphiphiles were investigated. Straightforward coupling of hydrophilic unprotected sugar and hydrophobic high molecular weight alcohols, in the presence of p-toluenesulfonic acid as a promoter, yielded structurally different compounds in very good yields (37–87%). A homologous series including 17 examples of alkyl α-l-rhamnoside amphiphiles varying in chain structure (C4–C20) is reported. The structures of the new derivatives were determined by NMR spectroscopy and quantum chemical calculations. Molecular geometry optimizations of different ring forms (1C4 and 4C1) and anomeric configurations were carried out using DFT calculations. Herein we demonstrate the advantages of microwave irradiation for the preparation of a broad variety of linear and branched-chain alkyl α-l-rhamnosides. The application of this approach to the synthesis of new natural non-ionic surfactants makes this method attractive because of their potential use in biomedical and pharmaceutical chemistry.

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1-Butyl l-rhamnopyranosideC10H20O5Ee = 100%[α]D20 = −60.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

2-Butyl l-rhamnopyranosideC10H20O5Ee = 100%[α]D20 = −78.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

iso-Butyl l-rhamnopyranosideC10H20O5Ee = 100%[α]D20 = −66.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

tert-Butyl l-rhamnopyranosideC10H20O5Ee = 100%[α]D20 = −64.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

iso-Amyl l-rhamnopyranosideC11H22O5Ee = 100%[α]D20 = −60.8 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

2-Pentyl l-rhamnopyranosideC11H22O5Ee = 100%[α]D20 = −76.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

1-Hexyl l-rhamnopyranosideC12H24O5Ee = 100%[α]D20 = −56.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

2-Hexyl l-rhamnopyranosideC12H24O5Ee = 100%[α]D20 = −58.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

4-Methyl-2-pentyl l-rhamnopyranosideC12H24O5Ee = 100%[α]D20 = −72.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

C13H26O51-Heptyl l-rhamnopyranosideEe = 100%[α]D20 = −54.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

1-Octyl l-rhamnopyranosideC14H28O5Ee = 100%[α]D20 = −45.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

2-Octyl l-rhamnopyranosideC14H28O5Ee = 100%[α]D20 = −37.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

1-Decyl l-rhamnopyranosideC16H32O5Ee = 100%[α]D20 = −41.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

1-Dodecyl l-rhamnopyranosideC18H36O5Ee = 100%[α]D20 = −29.3 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

C20H40O51-Tetradecyl l-rhamnopyranosideEe = 100%[α]D20 = −28.0 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

1-Hexadecyl l-rhamnopyranosideC22H44O5Ee = 100%[α]D20 = −33.3 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material

1-Eicosyl l-rhamnopyranosideC26H52O5Ee = 100%[α]D20 = −30.7 (c 1, CHCl3)Source of chirality: synthesis6-deoxy-l-Mannose (l-Rhamnose) as starting material