The effect of deoxyfluorination and O-acylation on the cytotoxicity of N-acetyl-d-gluco- and d-galactosamine hemiacetals

Abstract

Fully acetylated deoxyfluorinated hexosamine analogues and non-fluorinated 3,4,6-tri-O-acylated N-acetyl-hexosamine hemiacetals have previously been shown to display moderate anti-proliferative activity. We prepared a set of deoxyfluorinated GlcNAc and GalNAc hemiacetals that...

The Synthesis and Glycoside Formation of Polyfluorinated Carbohydrates

“…Azide reduction with concomitant acetylation then gave 1011. 463 Alternatively The Karban group also developed similar a synthesis of 3,6-difluorinated GalNAc derivative 1019 (Scheme 140). Starting again from 988, oxidative debenzylation followed by Lattrell-Dax inversion 276 resulted in the galacto-derivative 1016, which was protected as benzyl ether 1017.…”

“…146,451 Epoxide opening with lithium azide led to 1048 in 74% yield with a small amount of regioisomer 1049 observed. The alcohol group in 1048 was now acylated to give the acetate 1050a, 472 the propionate 1050b, and the butyrate 1050c, 463 as well as benzylated to give 1050d. 464 Anhydro-bridge cleavage was effected with PhSTMS to give a mixture of separable anomers 906a-d. 463,464 Interestingly, for the propionate derivative 1050b, a rearrangement byproduct 1051 was also isolated.…”

“…Sequential fluorination strategy via 1,6-anhydro derivatives to access 4,6-difluorinated GalNAc derivatives. 429,463 In Cabrera-Escribano's investigations of fluorinations on branched nitrosugars (cf. Scheme 132), 4,6dideoxy difluorination was also achieved from 925 (Scheme 144), which was obtained by benzylidene acetal deprotection of b-ent-926.…”

“…Schemes 128 and 129), to give the 4,6-difluorinated GlcNAc derivatives 1080a-c in high yield. 463 However, when the deoxyfluorination was carried out on the mixture of benzyl anomers 1078d, an excellent yield of 1080d was obtained with no mention of migration issues. reduced with concomitant acetylation to give 1082a-d. 429,463 The benzyl ether was then removed via hydrogenolysis to give 4,6-dideoxy-4,6-difluoroGlcNAc 1083.…”

“…Azide reduction with concomitant acetylation then gave 1011. 463 Alternatively, the 4-O-benzyl-protected 1,6-anhydro derivative 988, obtained in four steps from D-glucal as discussed in Scheme 137, was treated with PhSTMS to obtain a separable mixture of thioglycoside anomers α-and β-900. 464 These anomers were separated before deoxyfluorination, given the 1 → 6 migration side reaction of the β-thiophenyl anomer (see Schemes 128 and 129).…”