3453-00-7Relevant articles and documents
Novel cobalt(0)- or magnesium-mediated approaches to β-ketophosphonates
Orsini, Fulvia,Di Teodoro, Emanuela,Ferrari, Marinella
, p. 1683 - 1688 (2002)
Two novel approaches to β-ketophosphonates, based on cobalt(0)- or magnesium-mediated reactions of α-halophosphonates with esters are described.
Synthesis and antiproliferative evaluation of new zampanolide mimics
Chen, Guanglin,Patanapongpibul, Manee,Jiang, Ziran,Zhang, Qiang,Zheng, Shilong,Wang, Guangdi,White, James D.,Chen, Qiao-Hong
, p. 3830 - 3844 (2019)
(?)-Zampanolide is a marine microtubule-stabilizing macrolide that has been shown by in vitro experiments to be a promising anticancer lead compound. Through its unique covalent-binding with β-tubulin, zampanolide exhibits cytotoxic potency towards multi-drug resistant cancer cells that is superior to paclitaxel. However, the limited availability of zampanolide impedes its further in vivo evaluation as a viable drug candidate. Zampanolide is envisioned to become more drug-like if its chemically fragile side chain can be stabilized; hence, this project aims to develop mimics of zampanolide with a stable side chain using straightforward synthetic methods. To this end, twelve novel zampanolide mimics (51-62) with conjugated and planar side chains have been synthesized via a 24-step sequence for each mimic from commercially available 2-butyn-1-ol as starting material. A Horner-Wadsworth-Emmons reaction incorporates the α,β-unsaturated ketone side chain and also closes the core macrocycle. WST-1 cell proliferation assays in three docetaxel-sensitive and two docetaxel-resistant human prostate cancer cell models confirm that a suitably designed side chain can serve as a bioisostere for the N-acyl hemiaminal side chain in zampanolide. Mimic 52 with a 17R chiral center was identified as the optimal candidate with IC50 values of 0.29-0.46 μM against both docetaxel-sensitive (PC-3 and DU145) and docetaxel-resistant prostate cancer cell lines (PC-3/DTX and DU145/DTX). Zampanolide mimic 52 exhibited equivalent antiproliferative potency towards both docetaxel-sensitive and docetaxel-resistant cell lines, with relative resistance in the range of 0.9-1.6.
Copper-Catalyzed Microwave-Expedited Oxyphosphorylation of Alkynes with Diethyl Phosphite and t-Butyl Hydroperoxide Synthesis of Densely Functionalized Phosphonylated Indenones
Maciás-Benítez, Pablo,Sierra-Padilla, Alfonso,Tenorio, Manuel J.,Moreno-Dorado, F. Javier,Guerra, Francisco M.
, p. 16409 - 16424 (2021/11/16)
Treatment of alkynes with diethyl phosphite and t-butyl hydroperoxide in the presence of [Cu(MeCN)4]BF4 under microwave irradiation produced the oxyphosphorylation of the triple bond, giving rise to the corresponding β-ketophosphonates in moderate-to-good yields. When the triple bond was conjugated to a carbonyl group bearing an aromatic ring, it led to the cyclization of the resulting ketone intermediate, producing eventually different phosphonylated indenones.
Access to chiral α-substituted-β-hydroxy arylphosphonates enabled by biocatalytic dynamic reductive kinetic resolution
Chen, Fener,Huang, Zedu,Li, Zihan,Tao, Yuan,Wang, Zexu,Wu, Xiaofan,Yu, Xiaomin,Zeng, Yiping
supporting information, p. 2672 - 2677 (2020/04/17)
Ketoreductase (KRED)-catalyzed dynamic reductive kinetic resolution (DYRKR) of α-substituted-β-keto arylphosphonates was developed as a generic and stereoselective approach to synthesize chiral α-substituted-β-hydroxy arylphosphonates, with moderate-to-excellent isolated yield (up to 96%), good-to-excellent diastereoselectivity (up to >99 : 99% ee) being achieved.
