Synthesis and antiproliferative activities of OSW-1 analogues bearing 2-acylamino-xylose residues

Abstract

We synthesized 38 OSW-1 analogues with 2-acylamino xylose residues and found that the antitumor activities could be greatly enhanced.

Biological and Pharmacological Effects of Synthetic Saponins

“…Although the cytotoxicity was lower, compounds with complex acyl group on 2-N position of xylose (30) were found to increase the selectivity index. Besides, an analogue with photoaffinity and clickable moiety was also synthesized and can be applied to target identification in the future [63].…”

Synthesis and Antiproliferative Activities of OSW‐1 Analogues Bearing 2”‐O‐p‐Acylaminobenzoyl Residues†

“…In our previous studies, it was found that xylosyl donor 8 bearing BDA protecting group at O3 and O4 led mainly to the undesired (1→4)‐linked disaccharide product when coupled with L ‐arabinoside 3,4‐diol 10 , [ 35 ] whereas the glycosylation with TES‐protected donor 9 offered the desired (1→3)‐linked disaccharide as the major product (Figure 2). [ 8,11 ] In order to improve the regio‐selectivity and verify our assumption that these regio‐selectivities were mainly determined by the protecting groups at O3 and O4 of the donors instead of the substitutes at O2 or anomeric position, [ 50‐53 ] we envisioned the TES‐protected thioxyloside 11 as a counterpart of BDA‐protected 6 in the present studies (Scheme 2).…”

“…Next, the anomeric benzyl group on 26 was successfully removed by an enhanced 24‐h hydrogenolysis with an excess amount of Pd/C, and the resulting hemiacetal was coupled with alkynylbenzoic acid 14 . A Ph 3 PAuNTf 2 ‐catalyzed glycosylation was then conducted with either azido‐bearing aglycone 27 or alkyne‐bearing aglycone 28 at 0 o C (See SI for the preparation of 28 ), [ 35 ] and subsequent removal of the TES and Boc groups under the conditions of CF 3 COOH and CH 2 Cl 2 at rt furnished the desired OSW‐1 analogues 29 and 30 , which bear a 2‐ O ‐( p ‐amino‐benzoyl)‐xylose residue.…”

“…[ 28‐34 ] Very recently, we revealed that analogue 3 , with the original ester at the xylose residue being replaced by amide, displayed even stronger antitumor activities with the IC 50 value as low as 0.11 nM against Jurkat T cell lines. [ 35 ]…”

Development of Chemical Probes for Functional Analysis of Anticancer Saponin OSW‐1

“…[8] In contrast, a relatively few studies have been reported on the development of chemical probes of OSW-1 for investigation of its biological role. [4,9,10] Here, we summarize our recent efforts in the synthesis, biological properties of probes derived from naturally occurring OSW-1 and their application to the analysis of intracellular localization and the interaction with known target proteins.…”