Tetraoxane antimalarial

Studies on the mode of activity of the antimalarials related to artemisinin have centred on simpler 1,2,4-trioxanes, 1,2,4,5-tetraoxanes and bicyclic endoperoxides <00H(52)1345 00JCS(P1)1265 00JMC2753 00TL3145>. The chemical and electro-chemical reduction of artemisinin has been reported <00JCS(P1)4279>. 

Antimalarial activity is also shown by 13,43-tetraoxanes and these compounds have been synthesised by the acid-catalysed dimerisation of ozonides <99JMC2604>. Ozonolysis of vinyl ethers and cyclocondensation of the derived bis(hydroperoxides) with carbonyl... 

Tetraoxanes that show good antimalarial activity are formed when the steroid-derived gem/na/-dihydroperoxide 33 is treated with ketones <02JMC3331>. 

Since the 1990s, many research studies have demonstrated that 1,2,4-trioxanes and 1,2,4,5-tetraoxanes are important qinghaosu analogs. Some compounds are promising because of their high antimalarial activity and easy preparation. Some reviews about these peroxides have been pubhshed. ... 

Dispiro-l,2,4,5-tetraoxanes (45 1-3) were prepared with the intact peroxide functional group and tested for antimalarial activity [51], Dispiro-1,2,4,5-tetraoxanes, 1(5), 10( )-dimethyl-7,8,15,16-tetraoxodispiro[5,2,5,2]hexadecane (45 3) was as active as artemisinin, both in vitro and in vivo. Based on the resistance index (IC50(W-2)/IC5o(D-6)), 2,4,1 l,13-tetramethyl-7,8,15,16 tetraoxodispiro[5,2,5,2]hexadecane... 

General methods for the preparation of 1,2,4,5-tetraoxanes Key structures for the development of peroxidic antimalarial agents 12KGS60. Reactions oftetrazines with dienophiles 12KGS1237. 1,2,4,5-Tetrazines and azolo[l,2,4,5]tetrazines Synthesis and reactions with nucleophiles 13KGS75. 

Dong, Y McCullough, K.J., Wittlin, S Chollet, J., and Veimerstrom, J.L. (2010) The structure and antimalarial activity of dispiro-l,2,4,5-tetraoxanes derived from (-l-)-dihydrocarvone. Bioorg. Med. Chem. Lett., 20, 6359-6361. 

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