120314-20-7Relevant articles and documents
Total Synthesis of Aaptamine of Potent α-Blocking Activity via Thermal Cyclization of 1-Azahexatriene Systems
Hibino, Satoshi,Sugino, Eiichi,Choshi, Tominari,Sato, Kohichi
, p. 2429 - 2432 (2007/10/02)
The total synthesis of the marine alkaloid aaptamine (1), 1H-benzonaphthyridine, has been completed, based on the thermal cyclization of the 1-azahexatriene system, the key intermediate for the construction of the isoquinoline moiety. 5-Nitroveratraldehyde (7) is converted, via a Wittig reaction, into the nitrostyrene (8).Reduction of (8) to the aniline (9) and subsequent treatment of (9) with ethyl 2-formylacetate gives the enamino ester (10).Preparation of the quinolone nucleus is achieved by heating compound (10) in diphenyl ether, which affords the N-benzylquinolone (12) along with the quinoline (13).Treatment of an inseparable mixture of (12) and (13) with hydroxylamine gives the debenzylated quinolone oxime (11), methylation of which affords a separable mixture of the N,O-dimethyl quinolones (14) and (15).The methyloxime (14) (the 1-azahexatriene system) when heated in o-dichlorobenzene gives the unnatural 1-methylaaptamine (3).In a similar way, benzylation of (15) affords the N,O-dibenzyl quinolone derivatives (16) and (17).The benzyloxime (16) when heated in o-dichlorobenzene affords N-benzylaaptamine (18).Subsequent cleavage of the N-benzyl protecting group with concentrated hydrochloric acid gives aaptamine hydrochloride (1).
