35274-53-4Relevant articles and documents
Microwave-enhanced synthesis of N-shifted buflavine analogues via a Suzuki-ring-closing metathesis protocol
Appukkuttan, Prasad,Dehaen, Wim,Van Der Eycken, Erik
, p. 2723 - 2726 (2005)
(Chemical Equation Presented) A novel, microwave-enhanced six-step synthesis was devised for the synthesis of N-shifted buflavine analogues. Microwave-enhanced Suzuki-Miyaura cross-coupling and ring-closing metathesis reactions were used as the key steps. Microwave irradiation was found to enhance the ring-closing metathesis reaction to generate the otherwise difficultly obtainable medium-sized ring system of the target molecules.
Synthesis of substituted biphenyl methylene indolinones as apoptosis inducers and tubulin polymerization inhibitors
Donthiboina, Kavitha,Anchi, Pratibha,Sri Ramya,Karri, Shailaja,Srinivasulu, Gannoju,Godugu, Chandraiah,Shankaraiah, Nagula,Kamal, Ahmed
, p. 210 - 223 (2019)
A new series of biphenyl methylene indolinones has been designed, synthesized and evaluated for their in vitro antiproliferative activity against various cancer cell lines like DU-145 (prostate cancer cell line), 4T1 (mouse breast cancer cell line), MDA-MB-231 (human breast cancer cell line), BT-549 (human breast cancer cell line), T24 (human urinary bladder carcinoma cell line), and HeLa (cervical cancer cell line). Among the series, compound 10e showed potent in vitro cytotoxic activity against HeLa and DU-145 cancer cell lines with IC50 value of 1.74 ± 0.69 μM and 1.68 ± 1.06 μM respectively. To understand the underlying mechanism of most potent cytotoxic compound 10e, various mechanistic studies were carried out on DU-145 cell lines. Cell cycle analysis results revealed that these conjugates affect both G0/G1 and G2/M phase of the cycle, tubulin binding assay resulted that compound 10e interrupting microtubule network formation by inhibiting tubulin polymerization with IC50 value of 4.96 ± 0.05 μM. Moreover, molecular docking of 10e on colchicine binding site of the tubulin explains the interaction of 10e with tubulin. Clonogenic assay indicated inhibition of colony formation by compound 10e in a dose dependent manner. In addition, morphological changes were clearly observed by AO/EB and DAPI staining studies. Moreover, ROS detection using DCFDA, JC-1, and annexin V-FITC assays demonstrated the significant apoptosis induction by 10e.
6,7-Benzotropolone Syntheses Based on Ring-Closing Metatheses and Four-Electron Oxidations
Brückner, Reinhard,Fernandes, Manuel A.,Gemander, Manuel,Green, Ivan R.,Kreibich, Michael,Peter, David,Yadav, Dharmendra B.,de Koning, Charles B.,van Otterlo, Willem A. L.
, (2020/05/18)
Four homoallyl ortho-vinylaryl ketones (10a-d) – 1,8-dienes of sorts – were prepared by several approaches. In the presence of 1–2 mol-% Grubbs-II catalyst, they ring-closed to give 6,7-dihydrobenzocyclohepten-5-ones (11a-d) in 90–96 % yield. With SeO2 the parent compound (11a) delivered benzocyclohepten-5-one (13a) and/or selenium-containing compounds (18–22) but no more than traces of 6,7-benzotropolone (5a). However, 5a was accessible from compound 11a via the sodium enolate and allowing it to react with a stream of oxygen (43 % yield). The sodium enolates of the substituted 6,7-dihydrobenzocyclohepten-5-ones 11b–d and oxygen underwent analogous 4-electron oxidations. This furnished the substituted 6,7-benzotropolones 11b-d. In contrast, the corresponding lithium enolates were inert towards oxygen. The 6,7-dihydrobenzocyclohepten-5-one 11d was also accessed differently, namely by a Grubbs-II catalyst-mediated RCM/C=C migration tandem reaction of the allyl ortho-allylaryl ketone 73 – another 1,8-diene of sorts (90 % yield).
An Enantioselective Total Synthesis of (+)-Duocarmycin SA
Schmidt, Michael A.,Simmons, Eric M.,Wei, Carolyn S.,Park, Hyunsoo,Eastgate, Martin D.
supporting information, p. 3928 - 3940 (2018/04/14)
An efficient, concise enantioselective total synthesis of the potent antitumor antibiotic (+)-duocarmycin SA is described. The invented route is based on a disconnection strategy that was devised to facilitate rapid and efficient synthesis of key core compounds to enable preclinical structure-activity relationship investigations. The key tricycle core was constructed with a highly enantioselective indole hydrogenation to set the stereocenter and a subsequent hitherto unexplored vicarious, nucleophilic-substitution/cyclization sequence to effectively forge a final indole ring. Additionally, the development of a stable sulfonamide protecting group capable of mild chemoselective cleavage greatly enhanced sequence yield and throughput. An understanding of key reaction parameters ensured a robust, reproducible sequence easily executable on decagram scales to this highly promising class of compounds.
