Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals.

1-C and 2-C-branched carbohydrates are present as substructures in a number of biologically important compounds. Although the synthesis of such carbohydrate derivatives is extensively studied, the synthesis of 1,2-cis-2-C-branched C-, S-, and N-glycosides is less explored. In this article a synthetic strategy for the synthesis of 1,2-cis-2-C-branched-aryl-C-glucosides is reported via a hydrogenolytic desulfurization of suitably orientated carbohydrate based hemithioacetals. 1,2-cis-2-Hydroxymethyl and 2-carbaldehyde of aryl-C-glucosides have been synthesized using the current strategy in very good yields. The 2-carbaldehyde-aryl-C-glucosides have been identified as suitable substrates for the stereospecific preparation of 2,3-unsaturated-aryl-C-glycosides (Ferrier products).

Stereoselective synthesis of thiochromenes via intramolecular tandem thio-Michael addition of in situ generated α,ß-unsaturated aldehydes.

An efficient and highly stereoselective strategy for the synthesis of 2,3-substituted thiochromenes having a complex and easily transformable group at the stereogenic center has been developed via a tandem thio-Michael addition reaction of an in situ generated α,ß-unsaturated aldehyde sugar derivative. The protocol is superior to reported protocols in that the carbohydrate-derived substituent at the stereogenic center of the thiochromene is versatile and is amenable for further transformation.

Phenyl 4,6-di-O-acetyl-2,3-dide-oxy-1-thio-α-d-erythro-hex-2-enopyran-oside.

The pyranosyl ring in the title compound, C(16)H(18)O(5)S, adopts an envelope conformation, with the acetyl groups in equatorial positions. In the crystal, weak C-H⋯O inter-actions link the molecules into chains.

Lerisetron Analogues with Antimalarial Properties: Synthesis, Structure-Activity Relationship Studies, and Biological Assessment.

A phenotypic whole cell high-throughput screen against the asexual blood and liver stages of the malaria parasite identified a benzimidazole chemical series. Among the hits were the antiemetic benzimidazole drug Lerisetron 1 (IC50 NF54 = 0.81 µM) and its methyl-substituted analogue 2 (IC50 NF54 = 0.098 µM). A medicinal chemistry hit to lead effort led to the identification of chloro-substituted analogue 3 with high potency against the drug-sensitive NF54 (IC50 NF54 = 0.062 µM) and multidrug-resistant K1 (IC50 K1 = 0.054 µM) strains of the human malaria parasite Plasmodium falciparum. Compounds 2 and 3 gratifyingly showed in vivo efficacy in both Plasmodium berghei and P. falciparum mouse models of malaria. Cardiotoxicity risk as expressed in strong inhibition of the human ether-a-go-go-related gene (hERG) potassium channel was identified as a major liability to address. This led to the synthesis and biological assessment of around 60 analogues from which several compounds with improved antiplasmodial potency, relative to the lead compound 3, were identified.

NaHSO(4) supported on silica gel: an alternative catalyst for Ferrier rearrangement of glycals.

NaHSO(4) supported on silica gel catalyses the Ferrier rearrangement reaction of 3,4,6-tri-O-acetyl-D-glucal with alcohols and thiols to give the corresponding 2,3-unsaturated glycosides in high anomeric selectivity and good to excellent yield in short reaction time.