From D‐Glucose to Biologically Potent L‐Hexose Derivatives: Synthesis of α‐L‐Iduronidase Fluorogenic Detector and the Disaccharide Moieties of Bleomycin A₂ and Heparan Sulfate

Abstract

A novel and convenient route for the synthesis of biologically potent and rare L-hexose derivatives from D-glucose is described. Conversion of diacetone-alpha-D-glucose (14) into 1,2:3,5-di-O-isopropylidene-beta-L-idofuranose (19) was efficiently carried out in two steps. Orthogonal isopropylidene rearrangement of compound 19 led to 1,2:5,6-di-O-isopropylidene-beta-L-idofuranose (27), which underwent regioselective epimerization at the C3 position to give the L-talo- and 3-functionalized L-idofuranosyl derivatives. Hydrolysis of compound 19 under acidic conditions furnished 1,6-anhydro-beta-L-idopyranose (35) in excellent yield, which was successfully transformed into the corresponding L-allo, L-altro, L-gulo, and L-ido derivatives via regioselective benzylation, benzoylation, triflation and nucleophilic substitution as the key steps. Applications of these 1,6-anhydro-beta-L-hexopyranoses as valuable building blocks to the syntheses of 4-methylcoumarin-7-yl-alpha-L-iduronic acid and the disaccharide moieties of bleomycin A(2) as well as heparan sulfate are highlighted.

Glycosylations of Simple Acceptors with 2‐O‐Acyl l‐Idose or l‐Iduronic Acid Donors Reveal Only a Minor Role for Neighbouring‐Group Participation

“…The 1 H NMR spectrum of the orthoester 7 had two sets of signals due to the presence of two diastereoisomers in a ratio of 10:3. Hung has also reported the formation of orthoester as the major product on subjecting a similar α‐ l ‐glycosyl chloride to glycosylation with methanol using AgOTf as promoter . Similarly, Whitfield[9b] reported that glycosylation of methanol with a related IdoA‐configured glycosyl bromide also gave orthoester as the major product and interestingly, the β‐ l ‐glycoside as a minor product with no trace of α‐ l ‐glycoside.…”

“…Despite earlier reports, of the successful synthesis of 3 using titanium tetrabromide, in our hands the bromide 3 was found to be highly reactive and unstable. Hung has also reported that a similar l ‐idosyl bromide is unstable and is readily hydrolyzed to the hemiacetal …”

Improvement on the Synthesis of Primary Amino Sugar Derivatives <i>via</i> <i>N</i>-Benzyl Intermediates

“…Compounds 1a-1d were chosen as model structures, to investigate the potential of benzylamine in promoting the substitution of the tosylate group (Figure 1). Isopropylidene acetals 1a [25], 1b [26] and 1c [10,27] were synthesized according to literature procedures. Whereas 1d was achieved from the elaboration of known dimethyl ether 4 [28] which was treated initially with aqueous (aq.)…”

“…Isopropylidene acetals 1a [25], 1b [26] and 1c [10,27] were synthesized according to literature procedures. Whereas 1d was achieved from the elaboration of known dimethyl ether 4 [28] which was treated initially with aqueous (aq.) 60% acetic acid (AcOH) to obtain 5 in 72% yield [29].…”

Fluorescently labelled glycans and their applications

“…Commercially available from the 1960s, 4-methylumbelliferyl glycosides, such as 4-methylumbelliferyl-α/β-D-glucopyranoside, 4-methylumbelliferyl-β-D-cellobioside, 4-methylumbelliferyl-β-D-galactopyranoside, and 4-methylumbelliferyl-N-acetyl-β-Dglucosaminide, have been used for the identification, characterization and kinetic study of glycosidases [58][59][60][61]. Cleavages of the glyco linkage in these glycosides, such as 4-methylumbelliferyl-β-D-glucopyranoside 22, by glycosidases lead to the formation of fluorescent 4-methylumbelliferone 23 (Scheme 4).…”