Action of Nitrating Mixtures and Mineral Acids on the Quinoline Alkaloids Haplophyllidine and Anhydroperforine

The effects of various acids on the intramolecular cyclization of haplophyllidine ( 1 ) were studied. Compound 1 was converted at room temperature by H 2 SO 4 , HNO 3 , HClO 4 , and a nitrating mixture into anhydroperforine ( 2 ) whereas AcOH and HCl (35%) did not affect 1 . Nitration of 1 and 2 at 65–70°C led to elimination of MeOH followed by aromatization of ring A and nitration of the furan ring to form 7-methoxy-3,3-dimethyl-9-nitro-2,3-dihydro-1 H -furo[2,3-b]pyrano[2,3-h] quinoline ( 3 ) and 7-methoxy-3,3-dimethyl-9-nitro-2,3,8,9-tetrahydro-1 H -furo[2,3-b]pyrano[2,3-h]quinolin-8-ol ( 4 ). Use of Ac 2 O and HNO 3 gave 4,8-dimethoxy-8-(3-methylbut-2-en-1-yl)-5,6,7,8-tetrahydro-furo[2,3-b]quinolin-7-yl nitrate ( 5 ). The structures of the synthesized compounds were elucidated using 1D and 2D NMR spectral data, X-ray crystal structure analyses, and DFT quantum chemical methods in the B3LYP/6-31g(d) approximation to calculate the UV and circular dichroism (ECD) spectra of 4 .