The trisaccharide 2,3,4-O-tribenzyl-a-L-rhamnosyl-(1→3)-4-O-acetyl-2-O-benzoyl-(1→2)-4-O-acetyl-3-O-benzoyla-L-rhamnosyl-1-(4-tolyl)thio-a-L-rhamnopyranoside was prepared from the thio-sugar 1-(4-tolyl)thio-a,b-L-rhamnopyranoside from the nonreducing end to the reducing end. The two acceptors possessing 2-and 3-OH groups for the construction of the trisaccharide were obtained from a 2,3-benzylidine-protected thio-sugar in a one-pot deprotection manner in a respective ratio of 1:2.5. As donors for glycosylation, the thio-sugars of both mono-and disaccharides were converted to trichloroacetimido rhamnosides. Through this chemoselective strategy, a trisaccharide was obtained that retained an anomeric thio group for coupling with ceramide moieties. Bioassays are in progress.

We constructed a minilibrary using a solution-phase synthesis through coupling of three core amino compounds (5'-amino-5'-deoxy uridine, 5'-amino-2',5'-di-deoxy arabinosyl uridine, and butan-1-amine) with 30 carboxylic acids via amide bond formation. The simplified structural core compound butan-1-amine was selectively coupled with 9 carboxylic acids as control. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay of the crude mixtures showed that analogues derived from fenbufen, butylfenbufen C15; ethacrynic acid, butyl ethacrynic amide C18; and sphingosines, Sph-1, Sph-2 and U27 had an increased cytotoxicity against MCF-7 cells as well as A549 cells. Structural elucidation with molecular docking suggested that cytotoxicity of these compounds is mainly due to the inhibition of enzymes regulating cellular apoptosis.

1-Aminophytosphingosine and 6-aminogalactosyl phytosphingosine were prepared in 61% and 40% yield libraries with 44 carboxylic acids showed that a 4-butylbenzoic acid-derived product exe, respectively. Glycosylation using benzoylprotected lipid resulted in better -selectivity for ceramide analogs, but the yield was less than that obtained with benzyl moieties. Screening the amide rted less cytotoxicity. These analogs were purified for validation of immunological potencies and the -GalCer analog but not the sphingosine analog stimulated human iNKT cell population.

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