Glycomimetics:  A Versatile de Novo Synthesis of β-1-C-Aryl-deoxymannojirimycin Analogues

Abstract

The synthesis of 11 β-1-C-aryl-deoxymannojirimycin analogues using a versatile de novo strategy is described. The origins of this report are derived from several recent developments in the area of C1-substituted glycomimetic polyhydroxylated piperidines. This study is designed as a structure−activity comparison to explore the effects of aryl substitution on the ability of the title compounds to inhibit glycosidase enzymes. The polyhydroxylated piperidine ring was constructed using vinyl bromide 10, which was synthesized in six steps from the bromobenzene microbial oxidation metabolite bromo diol 9. A palladium-catalyzed Suzuki cross-coupling of vinyl bromide 10 and the corresponding arylboronic acid served as the key pseudoanomeric carbon−carbon bond-forming step. Ozonolysis and selective reduction of the resultant carbonyl functions followed by reductive amination served to produce the azasugar ring. The complete NMR analysis of the resultant piperidine ring stereochemistry is also discussed. Fully deprotected β-1-C-aryl-deoxymannojirimycin analogues 8·HCl were obtained upon acidic deprotection.

Tactics and strategies for the synthesis of iminosugar C-glycosides: a review

“…45 Johnson et al also applied the ozonolysis and selective reduction protocole to access b-1-C-aryl-1-deoxymannojirimycin analogues (Scheme 18). 46 An elegant synthesis of b/b tethered polyhydroxylated ring systems (bis-imino-C-glycosides) has also been reported and further highlights the versatility of Johnson's strategy (Scheme 19). 47 The double reductive amination of the bis-keto amine obtained after the reduction of the ozonolysis product afforded the expected b/b C 8 linked bis-iminosugar 37 as a single diastereoisomer in good yield from 36 (Scheme 19).…”

Neue Erkenntnisse über Hemmung, Struktur und Mechanismus konfigurationserhaltender Glycosidasen

“…Abbildung [175] Isofagomin, [155] Valienamin, [176] 1-Desoxynojirimycin, [177±180] 1-Desoxymannojirimycin [181,182] und anderen Azasacchariden. [183±190] Da die Oximfunktion eines Hydroximsäurelactons oder -lactams in eine Richtung zeigt, die der Lage des Aglycons eines b-d-Glycosids näherkommt als jener eines a-Glycosids, sollte ein Oximsubstituent das Aglycon eines b-Glycosids besser nachahmen als jenes eines a-Glycosids; ein derart substituierter Inhibitor sollte b-Glycosidasen selektiver hemmen als die unsubstituierte Hydroximsäureverbindung.…”

Stille reaction over cis-halocyclohexadienediol derivatives

“…Reaction of the sterically hindered derivative 1k only afforded small amounts of 2k, and compound 1j showed no reaction. A more detailed observation of the results in [7][8][9] shows that compounds 1g and 1i were converted to the corresponding allyl derivatives in higher yields than 1h. These results outline the importance of the presence of an allylic hydroxyl moiety at the coupling partner, specially when it is arranged at the less hindered face, opposite to the isopropylidene group.…”

“…8 Also, results concerning the side chain modification of cis-diols on previously functionalized rings have been reported. 9 We based our study on Boyd's work 5 in which cis-cyclohexadienediols reacted with allyltributyltin in the presence of a palladium catalyst to replace bromine or iodine by an allyl group, forming allyl cis-dihydrodiols in low to moderate yields. We studied this reaction over several cis-dihydrodiol derivatives in order to obtain valuable synthons for our research program in natural products synthesis.…”

“…8 Also, results concerning the side chain modification of cis-diols on previously functionalized rings have been reported. [9][10][11][12][13][14][15] 0040-4039/$ -see front matter Ó …”