Synthetic acronycine

NATURAL AND SYNTHETIC ACRONYCINE DERIVATIVES MODIFIED AT THE PYRAN RING... 

There are different methods of the synthetic preparation of acronycine (W. M. Bandaranayake et al., J. Chem. Soc. Perkin 1, 998 (1968) J. Hlubucek et al. Aust. J. Chem. 23, 1881 (1970). One of them is described below. Friedel-Crafts condensation between 2-nitrobenzoyl chloride and 3,5-dimethoxyphenol. 

Acridines (Phe pyridine Phe) include arborinine from Ruta graveolens and other Rutaceae (a spasmolytic and A1 adenosine receptor antagonist) and the pyranoquinoline acronycine (with cytotoxic and antitumour activity) from Acronychia species and Melicope leptococca (Rutaceae) and which has become a useful lead compound for the synthesis of other anticancer compounds. A variety of synthetic acridines are DNA binding anticancer compounds. 

New synthetic work in this area has been limited to two reports," " one of which involved the preparation of acronycine (27) by two equally attractive routes from the acridone derivatives (25) and (26) respectively. ... 

Acronycine was first synthesized in 1967-68 by Beck et al. who published simultaneously three interrelated syntheses of that alkaloid (13, 14). Around ten other total syntheses have been reported up till now (15-26). Most of the synthetic strategies developped are sufficiently versatile to permit access to acronycine structural analogues as far as substitution on the A ring is concerned. Syntheses of analogues modified at B, C and D rings have been comparatively less explored. Most of them rely on chemical modifications performed on a preformed pyranoacridone skeleton, at the latest steps of the synthesis. 

A number of derivatives of acronycine, a variety of acridone alkaloids, some synthetic acridones, acridines and related compounds, have been studied for antitumour activity [94]. Only acronycine displayed activity, thus demonstrating a strict structure-activity relationship. Clinical studies on the drug have commenced, but no results have been published on the effectiveness of acronycine in the treatment of human neoplasms. 

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