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 H₂SO₄, HNO₃, HClO₄, 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-1H-furo[2,3-b]pyrano[2,3-h] quinoline (3) and 7-methoxy-3,3-dimethyl-9-nitro-2,3,8,9-tetrahydro-1H-furo[2,3-b]pyrano[2,3-h]quinolin-8-ol (4). Use of Ac₂O and HNO₃ 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.