THERMAL DEGRADATION AND MASS SPECTROMETRY OF BENZODIAZEPINE ALKALOIDS (-)-CYCLOPENINE AND (-)-CYCLOPENOL

(-)-Cyclopenine (I) and (-)-cyclopenol (II) are benzodiazepine derivatives formed by Penicillium viridicatum Westling and P. cyclopium Westling. They are easily transformed to the quinoline alkaloids viridicatine (III) and viridicatol (IV) respectively by a general acid catalysis or an enzyme of P. viridicatum called cyclopenase. Mass spectrometric investigations suggest that both benzodiazepine compounds may be converted to viridicatine and viridicatol by thermic degradation. In fact, by heating (-)-cyclopenine and (-)-cyclopenol in various solvents to 220-240°C they readily rearrange by loss of methyl isocyanate to viridicatine and viridicatol. Besides this major route of degradation there is a minor one giving rise to 3-methyl-3,4-dihydroquinazolone-(4), carbonmonoxide and benzaldehyde or m-hydroxybenzaldehyde. The pyrolysis presumably starts with the homolytic fission of the epoxide ring between the oxygen and either C-atom 10 or 3 and follows the route shown in Schemes 1 and 2. Degradation of biosynthetically labelled (-)-cyclopenol-2-14C, -3-14C and -5-14C supports the mechanisms proposed. It was possible to show that the carbonyl group of the methyl isocyanate derives from C (5) and the carbon monoxide from C (2) of the benzodiazepine ring. In the 3-methyl-3,4-dihydroquinazolone-(4) C-atoms 3 and 5, in the viridicatol C-atoms 2 and 3 of this ring remain (Table 1). By mass spectrometric degradation of (-)-cyclopenine and (-)-cyclopenol a set of peaks is obtained which corresponds to the molecular ions of viridicatine or viridicatol and their fragmentation products (Figs. 1-4). In addition there seem to be other fragmentation routes probably connected in part with a hydrogen shift from the side chain to the benzodiazepine moiety (Schemes 3 and 4), In spite of this 3-methyl-3,4-dihydroquinazolon-(4) may be formed in small quantities. Conversion of cyclopenine and cyclopenol to 3-methyl-1,2,3,4-tetrahydroquinazolindione-(2,4) was not detectable. © 1969.