Chiral Crown Ethers Based on Galactopyranosides

Abstract

The 1,4- and 1,6-bridged 20- and 23-membered galacto-crown ethers 7, 8 and 11 were synthesized by intramolecular transglycosidation of the phenyl 1-thio-d-galactopyranosides 5, 6, and 10, respectively. The relevant precursors 5, 6, and 10 were obtained from phenyl 2,3,6-tri-O-benzyl-1-thio-β-d-galactopyranoside (2) and phenyl 2,3,4-tri-O-benzyl-1-thio-β-d-galactopyranoside (3), respectively, via two etherification steps. Compounds 2 and 3 are accessible from the same precursor, phenyl 2,3-di-O-benzyl-4,6-O-benzylidene-1-thio-β-d-galactopyranoside (1), by regioselective opening of benzylidene acetal. O-Alkylation of 2 and 3 with bis(2-chloroethyl)ether gave phenyl 2,3,6-tri-O-benzyl-4-[2-(2-chloro-ethoxy)ethyl]-1-thio-β-d-galactopyranoside (4) and phenyl 2,3,4-tri-O-benzyl-6-[2-(2-chloro-ethoxy)ethyl]-1-thio-β-d-galactopyranoside (9), respectively. The ensuing chain elongation of 4 was carried out with triethylene glycol and tetraethylene glycol, respectively, yielding 5 and 6. Compound 9 was alkoxylated with tetraethylene glycol under the same reaction conditions yielding phenyl 2,3,4-tri-O-benzyl-6-O-{2-[ω-hydroxy-penta-(oxyethylene)ethyl]}-1-thio-β- d-galactopyranoside (10). The yields of the chiral crowns 7, 8 and 11, obtained in the final cyclization step from the thioglycosides 5, 6, and 10, are 32-61%, i.e., they could be more than doubled compared to previous experiments with O-glycosidic precursors. High β-stereoselectivity was found for the cyclizations to the 1,4-bridged crowns 7 and 8. In contrast, the more flexible 6-O-polyethylene derivative 10 cyclized exclusively to the 1,6-bridged α-glycosidic crown ether 11.

Key words

crown ethers - ansa-glycosides - 1-thio-galactopyranosides - polyethylene glycols - intramolecular glycosidation

References

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