113250-72-9Relevant academic research and scientific papers
Prodrug Activation by Gold Artificial Metalloenzyme-Catalyzed Synthesis of Phenanthridinium Derivatives via Hydroamination
Chang, Tsung-Che,Vong, Kenward,Yamamoto, Tomoya,Tanaka, Katsunori
, p. 12446 - 12454 (2021)
An emerging approach in the field of targeted drug delivery is the establishment of abiotic metal-triggered prodrug mechanisms that can control the release of bioactive drugs. Currently, the design of prodrugs that use abiotic metals as a trigger relies heavily on uncaging strategies. Here, we introduce a strategy based on the gold-catalyzed activation of a phenanthridinium-based prodrug via hydroamination under physiological conditions. To make the prodrug strategy biocompatible, a gold artificial metalloenzyme (ArM) based on human serum albumin, rather than the free gold metal complex, was used as a trigger for prodrug activation. The albumin-based gold ArM protected the catalytic activity of the bound gold metal even in the presence of up to 1 mM glutathione in vitro. The drug synthesized via the gold ArM exerted a therapeutic effect in cell-based assays, highlighting the potential usefulness of the gold ArM in anticancer applications.
A stereoselective intramolecular Diels-Alder strategy for the tricyclo[9.3.1.03,8]pentadecane core of aromatic C-ring taxanes
Smil, David V.,Laurent, Alain,Spassova, Nidejda S.,Fallis, Alex G.
, p. 5129 - 5132 (2007/10/03)
A stereoselective Lewis acid-catalyzed and chelation controlled intramolecular Diels-Alder entry into the tricyclo[9.3.1.03,8]pentadecane core of aromatic C-ring taxanes is described. The approach affords an efficient, high yield, access to aromatic C-ring taxanes variably functionalized at the C2, C4, C5, and C9 positions.
Synthesis of NK109, an anticancer benzo[c]phenanthridine alkaloid
Nakanishi, Takeshi,Suzuki, Masanobu,Mashiba, Akihiro,Ishikawa, Keizou,Yokotsuka, Takashi
, p. 4235 - 4239 (2007/10/03)
A total synthesis of NK109 (7-hydroxy-8-methoxy-5-methyl-2,3- methylenedioxybenzo[c]phenanthridinium hydrogensulfate dihydrate), an anticancer benzo[c]phenanthridine alkaloid, is reported. The primary structure of this compound was erroneously communicated in 1973 as fagaridine (from Fagara xanthoxyloides) which the 8-hydroxy regioisomer. NK109 has not yet been isolated from a natural source and therefore can only be obtained by synthesis. To study a wide variety of analogues, we decided to use a synthetic route via substituted benzylamine 5, which was obtained from the appropriate benzaldehyde ad naphthylamine units. The benzo[c]phenanthridine ring was conducted by radical cyclization with tri-n-octyltin hydride and 2,2'-azobis(2)-methylbutyronitrile], followed by oxidative aromatization with MnO2. The resulting benzo[c]phenanthridine 6 was successfully methylated with methyl 2-nitrobenzenesulfonate. After deprotection of the benzyl group and subsequent hydration, NK109 was obtained. All reactions were performed under normal conditions. Purification was achieved only by recrystallization to give an overall yield of 40%.
Benzyne Cyclization Route to Benzophenanthridine Alkaloids. Synthesis of Chelerythrine, Decarine, and Nitidine
Kessar, Satinder V.,Gupta, Yash P.,Balakrishnan, Prasanna,Sawal, Kewal K.,Mohammad, Taj,Dutt, Mahesh
, p. 1708 - 1713 (2007/10/02)
The alkaloids chelerythrine (8b) and decarine (7c) have been synthesized through a benzyne-mediated cyclization of N-(2-halobenzyl)-1-naphthylamines 4 with KNH2 in ammonia/ether.The 7-hydroxybenzophenanthridine structure 16a proposed for the alkaloid fagaridine is questioned on the basis of comparison with a model compound (16b) synthesized by benzyne cyclization.For the 8,9-oxygenated alkaloids like nitidine (8i), this cyclization proceeded poorly, but a dramatic improvement occurred when LDA/THF at -78 deg C was used instead of KNH2/NH3.
