Natural and synthetic quinonoid compounds are wellknown substances which possess a variety of biological properties such as antibacterial, antifungal, antiprotozoal, inhibition of the human immunodeficiency virus (HIV)-1 reverse transcriptase and antitumor activity.2-7) Some of these pharmacological effects have been attributed to the formation of DNA-damaging anion-radical intermediates formed by bioreduction of the quinone nucleus.8) Among heterocyclic quinones with cytotoxic activity, those containing a thiophene nucleus fused to a quinone system have received little attention 9,10) despite the antitumoral activity of thiophene analogues of daunomycin and mitoxantrone. 11,12) As part of a program directed towards the design and synthesis of carbo-and heterocyclic quinones as potential antiprotozoal agents, we have reported the synthesis and antiprotozoal activity of benzopyrano-and benzo [b]thiophenequinones. 1,13,14) Since the thiophene ring-containing quinones showed promising antiprotozoal activity against trypanosome cruzi and strains of Leishmania spp.1,14) we decided to continue the studies on synthesis and biological evaluation of new members of this series containing functional groups on C-2 and C-3 positions of the thiophene ring.This paper describes the preparation of functionalised benzo [b]thiophenes and their application to the synthesis of benzo-and naphthothiophenequinones with orthoaminoester functionality on the thiophene ring. Moreover we report the cytotoxic activity of the new quinones against Leishmania amazonensis and human-T-cell leukemia virus type 1 (HTLV-I), the causative agent of two well-defined diseases: adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/ HAM).
15)In a previous work we have described the synthesis of a variety of 2-substituted benzo [b]thiophene-4,7-quinones using a two step sequence which involves the reaction of dimethoxy-o-acylnitroarenes with methyl thioglycolate followed by oxidative deprotection of the corresponding dimethoxybenzo[b]thiophene with ceric ammonium nitrate (CAN).16) On the basis of these results we investigated the synthesis of ortho-aminoesters 5 via cyclisation of 3,6-dimethoxy-2-nitrobenzonitrile (3) with methyl thioglycolate. Compound 5 could be a valuable intermediate in the synthesis of angular tetracyclic thiophene-containing quinones due to the possibility to extend the bicyclic system through either the thiophene and/or the quinone rings.3,6-Dimethoxy-2-nitrobenzaldehyde (1), prepared as reported, 17) was converted into 2,5-dimethoxy-6-nitrobenzonitrile (3) in 54% total yield, by reaction with hydroxylamine followed by dehydration of 3,6-dimethoxy-2-nitrobenzaldehyde oxime (2) with acetic anhydride. The thiophene ring formation on 3 was attempted by reaction with methyl thioglycolate in N,N-dimethylformamide (DMF) using potassium carbonate however, methyl (2-cyano-3,6-dimethoxyphenylsulfanyl)acetate (4) was isolated as the main product along with small amounts of the methyl 3-amino-...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Benzothiophene derivativesBenzothiophene derivatives R 0100 Studies on Quinones. Part 37. Synthesis and Biological Activity of o-Aminoester Functionalized Benzo-and Naphtho[2,3-b]thiophenequinones. -The title compounds (VIII), (X) and (XI) are synthesized according to the scheme and their leishmanicidal and anti-HTLV-1 activity are investigated. -(VALDERRAMA*, J. A.; ASTUDILLO, C.; TAPIA, R. A.; PRINA, E.; ESTRABAUD, E.; MAHIEUX, R.; FOURNET, A.; Chem.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.