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
