Fig. 1

Structural representations of the trioxolanes, tetraoxanes and derivatives of artemisinin investigated in this work. Scheme 1: Representation of the synthetic routes to the trioxolanes prepared; reagents and conditions: (i) Pyridine, MeONH2, MeOH, r.t; (ii) 1,4-Cyclohexane, O3, DCM/pentane, − 78 °C; (iii) LC133, O3, DCM/pentane, − 78 °C; (iv) Ethyl 4-oxocyclohexanecarboxylate, O3, DCM/pentane, − 78 ºC; (v) LC64, AcOH, DCE, NaBH(OAc)3, r.t.; (vi) Trichloroacetic acid, DCM, H2O, r.t.; (vii) 5-Aminotetrazole, DCE, AcOH, NaBH(OAc)3, r.t.; (viii) LiBH4, Et2O, LiBH(Et)3, r.t.; (vi) KOH (3M), MeOH, 60 °C; (x) Phthalimide, Ph3P, DIAD, THF, 0ºC; (xi) Hydrazine hydrate, chloroform/MeOH, 60 °C; (xii) 3-Chloro-1,2-benzisothiazole-1,1-dioxide, THF, 60 °C; (xiii) 3-Chloro-1,2-benzisothiazole-1,1-dioxide, TEA, toluene, 45 °C; (xiv) 2-Methyl-2H-tetrazole-5-amine, TEA, mesyl chloride, THF, 60 ºC; (xv) 5-Chloro-1-phenyl-tetrazole, TEA, mesyl chloride, THF, 60 °C; (xvi) tert-Butyl(4-aminobutyl)carbamate, EDC, HOBt, N-methylmorpholine, DCM, r.t.; (xvii) Trichloroacetic acid, DCM, H2O, r.t.; (xviii) Butylamine, EDC, HOBt, N-Methylmorpholine, DCM, r.t.; (ix) 1-Aminobutane, EDC, HOBt, N-Methylmorpholine, DCM, r.t.; Scheme 2: Representation of the synthetic route to tetraoxanes LC140 and LC163; reagents and conditions: (i) HCO2H, CH3CN, H2O2 50%, 0 °C; (ii) 1,4-Cyclohexanone, DCM, HBF4, 0 °C; (iii) 5-Aminotetrazole, DCE, AcOH, NaBH(OAc)3, r.t.