New synthesis of pyrrolidine homoazasugars via aminohomologation of furanoses and their use for the stereoselective synthesis of aza-C-disaccharides.
The introduction of a formyl group at the anomeric center of 2,3,5-tri-O-benzyl furanoses and substitution of the ring oxygen with a basic nitrogen atom (aminohomologation) was carried out via stereoselective addition of 2-lithiothiazole to N-benzyl, N-furanosylhydroxylamines (masked N-benzyl sugar nitrones), followed by reductive dehydroxylation of the resulting open-chain adducts, and then ring closure via intramolecular displacement of the free hydroxy group by the amino group and unmasking of the formyl group from the thiazole ring. The resulting formyl aza-C-glycosides were transformed into 2,5-dideoxy-2,5-imino-hexitols (pyrrolidine homoazasugars) by reduction of the formyl to the hydroxymethyl group and removal of the O- and N-benzyl groups by hydrogenolysis. This reaction sequence was applied to four furanoses (D-arabino, D-ribo, D-lyxo, L-xylo) to give the hydroxy- and amino-free homoazasugars, including the natural product 2,5-dideoxy-2,5-imino-D-mannitol, in 17% overall yields (six steps). The formyl aza-C-glycosides proved to be valuable intermediates for the synthesis of more complex derivatives. In fact, these sugar aldehydes were employed in Wittig-type coupling reactions with galactose and ribose phosphoranes to give bis-glycosylated alkenes, which upon reduction of the double bond were transformed into methylene isosteres of (1-->6)- and (1-->5)-linked disaccharides in which one of the two sugar moieties was an azasugar (aza-(1-->x)-C-disaccharides).
Dondoni
Alessandro
A
Dipartimento di Chimica, Laboratorio di Chimica Organica, Università di Ferrara, Via L. Borsari 46, 44100 Ferrara, Italy. adn@dns.unife.it
Giovannini
Pier Paolo
PP
Perrone
Daniela
D
D001374:Azacitidine; D002236:Carbohydrate Conformation; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D005663:Furans / Q000737:chemistry; D007202:Indicators and Reagents; D008958:Models, Molecular; D009005:Monosaccharides / Q000737:chemistry*; D011759:Pyrrolidines; D013237:Stereoisomerism
D004187:Disaccharides; D005663:Furans; D007202:Indicators and Reagents; D009005:Monosaccharides; D011759:Pyrrolidines; D001374:Azacitidine