The synthesis and characterization of four novel boron-containing bibenzimidazoles related to the DNA minor groove binder Hoechst 33258 are reported. Such compounds, particularly their 1°B-enriched forms, have potential as agents for boron neutron capture therapy which is used in the treatment of cancers.

A series of compounds have been synthesized in which the basic 2-phenylbibenzimidazole structure of Hoechst 33258 has been modified to include various combinations of bromo, iodo, methoxy, amino, alkylamino and nitro groups in the terminal phenyl ring. Both sequential and convergent synthetic routes have been followed using coupling reactions of both imino ethers and aldehydes to 1,2-diamines. All these compounds were characterized by a combination of f.a.b. mass spectrometry and 'H and 13C n.m.r. spectroscopy including inverse detection of long-range heteronuclear CH correlations (HMBC).

The chemistry of the reaction between DNA and pNPH has been investigated by isolation and analysis of the chromogen. The perchlorate of the cationic chromo-gen was prepared from the reineckate by anion exchange chromatography, and samples from both DNA-pNPH and furfuryl alcohol-pNPH reaction mixtures were found to have identical i.r. and p.m.r. spectra. The data obtained from the p.m.r. spectra were consistent with a reaction scheme involving formation of a pyridazinium cation which subsequently yields the chromophore on treatment with alkali.

Abstvacf 3-Amino-64odoacridine (lo), 3,6-diiodoacridine (11) and 9-amino-2-ethoxy-64odoacridine (14) were prepared by iodide ion substitution of the corresponding diazonium salt whereas 3,6-diamino-4,5-diiodoacridine (12) and 6,9-diamino-2-ethoxy-5-iodoacridine (13) were prepared by direct iodination with iodide ion in the presence of chloramine-T. The latter reaction proceeded in relatively high yield and has been used for the synthesis of high specific activity '251-labelled compounds (12), (13). The 'H and 13C n.m.r. spectra of (10)-(14) and model compounds indicate higher electron density at C4(C5) than at C2(C7) in 3(6)-amino-substituted acridines in agreement with the observed pattern of electrophilic substitution.

Although the aminoacridines are probably best known for their classical bacteriostatic and bactericidal properties,l current interest in these compounds is aminoacridines are not available commercially and must be synthesized before proceeding with biological investigations; this communication reports a simple procedure for the synthesis of 3-aminoacridine (I) from 3,6-diaminoacridine (proflavine), which is commercially available.Previously, the most convenient method' for preparing 3-aminoacridine was from formic acid and 3-aminodiphenylamine (obtained by reduction of the corresponding nitro compound, prepared from 3-nitroacetanilide). The overall yield of 3-aminoacridine from 3-nitroacetanilide was about 43%.An early claim5 to have prepared 3-aminoacridine by diazotization of proflavine and subsequent reduction of the diazonium salt in ethanol, was later disputed.6 The method described here involves diazotization of crude 3-acetamido-6-aminoacridine, obtained by acetylation of proflavine, followed by reduction with hypophosphorous acid and subsequent hydrolysis. The yield of 3-aminoacridine from proflavine is about 48%.The identity of the product was confirmed by comparison with an authentic specimen of 3-aminoacridine prepared from 3-aminodiphenylamine. The i.r. spectra, melting points, and RF values (in various chromatographic systems) were identical and the p.m.r. spectrum of the synthetic sample was consistent with 3-aminoacridine.7 Both samples could be purified by sublimation at 200' at atmospheric pressure. The sublimate, fine yellow needles, melted at 223" whereas the m.p. of each of the unsublimed samples was 217-218". Sublimation also resulted in slight improvements in the quality of the p.m.r. and i.r. spectra.