A transesterification reaction is implicated in the covalent binding of benzo[b]acronycine anticancer agents with DNA and glutathion.

The benzo[b]acronycine derivative S23906-1 has been recently identified as a promising antitumor agent, showing remarkable in vivo activities against a panel of solid tumors. The anticancer activity is attributed to the capacity of the drug to alkylate DNA, selectively at the exocyclic 2-amino group of guanine residues. Hydrolysis of the C-1 and C-2 acetate groups of S23906-1 provides the diol compound S28907-1 which is inactive whereas the intermediate C-2 monoacetate derivative S28687-1 is both highly reactive toward DNA and cytotoxic. The reactivity of this later compound S28687-1 toward two bionucleophiles, DNA and the tripeptide glutathion, has been investigated by mass spectrometry to identify the nature of the (type II) covalent adducts characterized by the loss of the acetate group at position 2. On the basis of NMR and molecular modeling analyses, the reaction mechanism is explained by a transesterification process where the acetate leaving group is transferred from position C-2 to C-1. Altogether, the study validates the reaction scheme of benzo[b]acronycine derivative with its target.

Chemistry of acronycine, XII. Further oligomers of noracronycine.

The polymerization of noracronycine (2) with methanolic HCl has yielded a second tetramer of 2, designated as AB-4 and determined to have the structure 7 through spectroscopic analysis. Two further pentamers of 2, designated as AB-6A and AB-6B, have also been obtained, and their structures are tentatively proposed as 9 and 5, respectively.

Chemistry of acronycine, XI. Rearrangement of dihydronoracronycine to dihydroisonoracronycine-mechanistic studies.

The rearrangement of dihydronoracronycine (3) to dihydroisonoracronycine (4) proceeds by way of an intermolecular reaction rather than an intramolecular reaction as had originally been supposed. Deuterium-labeling studies showed the incorporation of deuterium at C3, C12, and the geminal methyl positions of dihydroisonoracronycine (4). Because no reaction occurred when the bisnor derivative was treated in the same manner as 3, it appears that the chromene geminal methyl groups are important for the rearrangement to occur.

Analysis of the prodrug 7-acetylacroninium perchlorate in presence of the parent compound acronine.

Analysis of acronine and the prodrug acetylacroninium perchlorate in parenteral solutions is described. The unstable prodrug reacts quantitatively with the nucleophilic agent aniline by an unusual mechanism to form a phenylimino derivative of acronine. This derivative and acronine itself were determined by a spectrophotometric two-component method.