Synthesis of a fluorescent photoaffinity probe of OSW-1 by site-selective acylation of an inactive congener and biological evaluation

Abstract

A novel fluorescent photoaffinity probe of OSW-1 was prepared in two steps from a naturally occurring inactive congener by a sequential site-selective acylation strategy using MeSnCl. It displayed highly potent anticancer activity and a similar intracellular localization property to that of a fluorescently-tagged OSW-1, thereby demonstrating its potential utility in live cell studies.

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

“…[ 28‐34,36‐41 ] It is of great interest to identify the antitumor‐associated binding proteins, which could be exploited as drug targets for cancer treatment. Recently, Sakurai and co‐workers synthesized several OSW‐1‐based probes with fluorescent tags installed at C3” or C4” on the xylose residue, [ 42‐47 ] and found these probes could localize to the ER and Golgi apparatus in HeLa cells and induce Golgi stress. [ 41 ]…”

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

“…To simplify the synthetic scheme, a fluorescent tag was introduced to C4′′‐OH of OSW‐1. We envisioned that probe 16 could be synthesized by sequential acylation of a naturally occurring deacylated OSW‐1 ( 2 , Scheme ) at C4′′‐OH and then at C2′′‐OH by using Me 2 SnCl 2 . Treatment of 5 under the Me 2 SnCl 2 ‐mediated acylation conditions using acid chloride 15 gave the desired C2′′‐OH acylated product in 50 % (62 % brsm).…”

“…The Me 2 SnCl 2 -mediated site-selective acylation method was applied to synthesize fluorescent probes 5 using the deacylated OSW-1 2 with six hydroxyl group and the acetylated OSW-1 6 using the dideacylated OSW-1 3 with seven hydroxyl groups. Deacetylated congeners were successfully acylated at C4''-OH to give 5 in a 50 % yield (62 %, based on the recovered starting material, brsm) [15] and 6 in 48 % (58 %, brsm). [16] The fluorescent probes 4-6 were tested using XTT assay for their antiproliferative activity in HeLa cells.…”

“…We envisioned that probe 16 could be synthesized by sequential acylation of a naturally occurring deacylated OSW-1 (2, Scheme 4) at C4''-OH and then at C2''-OH by using Me 2 SnCl 2 . [15] Treatment of 5 under the Me 2 SnCl 2 -mediated acylation conditions using acid chloride 15 gave the desired C2''-OH acylated product in 50 % (62 % brsm). While extensive structure-activity relation- ship studies have been conducted for OSW-1, probe 16 represented the first example in the synthetic modification of the biologically essential C2''-moiety.…”

Design, Synthesis, and Biological Application of Novel Photoaffinity Probes of Dihydropyridine Derivatives, BAY R3401

“…Photoaffinity labeling is one of the major methods to directly capture small-molecule binding proteins [5]. The conventional approach, however, usually relies on the synthesis of photoaffinity probes and the identification of photolabeled fragments in proteins [6].…”