Syntheses and Bioactivities of Substituted 9,10-Dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrones. Unusual Reactivities with Amines

Abstract

A number of substituted 9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrones have been synthesized and their anticancer and antimalarial activities evaluated. A one-pot synthesis of 2,5,8-trimethoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4-dione (4) was achieved by heating a mixture of 1,4-dimethoxyanthracene, methoxyhydroquinone, silver oxide, and zinc iodide in toluene. Regioselective bromination of 4 and 2-methoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone (7) with N-bromosuccinimide provided 2-bromo-3,5,8-trimethoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4-dione and 2-bromo-3-methoxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone (1), respectively. The reactions of 1 with aliphatic primary amines and secondary amines, respectively, produced different products, a result most likely attributed to the different basicities (or nucleophilicities) and steric effects of the two kinds of amines. The structure of the displacement product, 2-bromo-3-[2-(tert-butoxycarbonyl)ethylamino]-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4,5,8-tetrone, from the reaction of 1 with tert-butyl 3-aminopropanoate was unequivocally determined by a single-crystal X-ray analysis. IC(50) values of triptycene bisquinones for the inhibition of L1210 leukemia cell viability are in the 0.11-0.27 microM range and for the inhibition of Plasmodium falciparum 3D7 are in the 4.7-8.0 microM range.

Saturation Mutagenesis of Burkholderia cepacia R34 2,4-Dinitrotoluene Dioxygenase at DntAc Valine 350 for Synthesizing Nitrohydroquinone, Methylhydroquinone, and Methoxyhydroquinone

“…Catechol, resorcinol, and hydroquinone are produced worldwide at 25,000, 35,000, and 50,000 tons per year, respectively, and are valuable as precursors for food, pharmaceutical, and industrial compounds (19). Methoxyhydroquinone is used in the synthesis of triptycene quinones for treatment of leukemia (20), and methylhydroquinone is used in the synthesis of (Ϯ)-helibisabonol A and puraquinonic acid, which are precursors for herbicides and antileukemia drugs, respectively (17,27). Nitrohydroquinone is used in the synthesis of dephostatin, an inhibitor of the protein tyrosine phosphatase (16), which holds promise for treating diabetes mellitus, Alzheimer's disease, and Parkinson's disease (44).…”

Total Syntheses of Cytotoxic, Naturally Occurring Kalasinamide, Geovanine, and Marcanine A

“…[22] TMS-I mediated demethoxylation [12] at the pyridine residue provided geovanine (3) in good yield (Scheme 5).…”

H3PW12O40‐Catalysed Alkylation of Arenes and Diveratrylmethanes: Convenient Routes to Triarylmethanes and to Symmetrical and Unsymmetrical 9,10‐Diaryl‐2,3,6,7‐tetramethoxyanthracenes

“…[21] Anthracenes have also been used in Diels-Alder reactions. [22] These compounds are generally prepared through Friedel-Crafts reactions, [6,11,23] aromatic cyclodehydration, [24] Haworth reactions, [25] Lewis-acid-induced Bradshare-type reactions from diveratrylmethanes, [26] Elbs reactions, [27] twofold SuzukiMiyaura cross-coupling reactions, [28] coupling reactions between zirconacyclopentadienes and dihalonaphthalenes, [29] cyclization of diacetates with TfOH, [30] H 2 SO 4 -catalysed reactions between benzocrown ethers and aldehydes, [31] and addition of Grignard reagents or aryllithiums to anthraquinones followed by reduction of the resulting diols. [32] The use of Keggin-type heteropolyacids as homogeneous or heterogeneous catalysts in organic synthesis has been developed as a result of their several advantages, such as environmental compatibility, reusability, non-corrosiveness and relative lack of disposal problems, which make them economically and environmentally attractive.…”