81969-62-2

Provided are molecules capable of binding to binding pockets of Plasmodium falciparum hexose transporter (PfHT) or analogs thereof and complexes comprising the same. Also provided herein are inhibitors of PfHT, pharmaceutical compositions comprising the i

A convenient method for conversion of sugar diols (2a-2d) into a-acetoxy-aldehydes: 5-O-acetyl-3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranos-6-ulose (5a), 5-O-acetyl-3-O-benzyl-1,2-O-isopropylidene-α-D-allofuranos-6-ulose (5b), methyl 6-O-acetyl-2,3,4-tri-O-benzyl-D-glycero-α-D-gluco- and L-glycero-α-D-gluco-heptopyranosid-7-uloses (5c and 5d respectively) is presented. This involves the protection (as TBDMS ether) of the primary hydroxyl group, acetylation of the remaining secondary one and desilylation followed by a Swern oxidation. Partial migration of the acetyl group during desilylation (with Bu4NF) was observed for compound 4a and complete migration for 4f. α-Acetoxy-aldehydes 5a-5d were characterized as adducts with Ph3P = CH-CO2Me (12a-12d).

The synthesis of 1,2-anhydromanno-, -lyxo-, -gluco-, and -xylofuranose benzyl ethers was successfully achieved via intramolecular S(N)2 reaction of the corresponding C-1 alkoxide with C-2 bearing tosyloxy group. The key intermediates, furanose 2-sulfonate

The acid-catalyzed solvolysis of methyl 3,5,6-tri-O-benzyl-2-O-(2-hydroxypropyl)-α-D-glucofuranoside (1) in chloroform involves a neighboring-group attack on C-1 by the hydroxypropyl substituent, and opening of the furanoside ring to yield a diastereomeric pair of 3,5,6-tri-O-benzyl-1-Omethyl-1,2-O-(1-methyl-ethanediyl)-D-glucose acetals (2 and 3).The latter, which differ in configuration at C-8,represent a resolution of the enantiomeric forms of the original 2-O-(2-hydroxypropyl) group.In a succeeding reaction, the 1-methoxyl group of each acetal undergoes an intramolecular displacement by O-4, leading to the formation of the corresponding biycyclic acetals, i.e., the two diastereomers (4 and 5) of 3,5,6-tri-O-benzyl-1,2-O-(1-methyl-1,2-ethanediyl)-α-D-glucofuranose.Solvolysis of 6, the β anomer of 1, proceeds in an analogous manner, although more rapidly, to yield a corresponding pair of acyclic-aldose acetals (7 and 8), as well as bicyclic acetals 4 and 5.Similar results are observed for solvolysis in the 2-O-(2-hydroxyethyl) series, whereas the reaction of the 2-O-(2,3-epoxypropyl) counterpart of 1 (or 6) with hydrogen chloride affords the corresponding chloromethyl analogs of 4 and 5.In all of these series, one of each diastereomeric pair of products is more stable than the other, and reasons for this are considered.Evidence based on n.m.r.-spectral data and steric factors is presented to show that the configuration of the chiral center C-8 of 2, 4, and 7 is (S), whereas it is (R) in 3, 5, and 8.Also, conformational characteristics of the various solvolysis products are assessed, and mechanisms possibly involved in their formation are discussed.

The title compound 13 is prepared on different routes from suitable benzyl derivatives with gluco-configuration.Preparations use the susceptibility of axial 5-O-benzyl groups in this compounds to selective hydrogenolysis, thus allowing subsequent inversion of configuration in this position from D-gluco to L-ido by an oxidation/reduction sequence.Only 0.08percent of 13 are found in the equilibrium mixture of idose in acidic medium.It is shown with 4-C-methyltalose as example, that the amount of 1,6-anhydrofuranoses in these equilibria rises significantly by changing the hydroxy groups in 4-position from secondary to tertiary ones.