Synthesis of the parent and substituted tetracyclic ABCD ring cores of camptothecins via 1-(3-aryl-2-propynyl)- 1,6-dihydro-6-oxo-2-pyridinecarbonitriles.
A new synthetic pathway to the parent and substituted ABCD ring cores of the camptothecin family of alkaloids was developed. The N-alkylation of 1,6-dihydro-6-oxo-2-pyridinecarbonitrile (2) with 3-bromo-1-phenylpropyne provided 3a using Curran's protocol. Treatment of 3a with a catalytic amount of DBU (5 mol %) at 110 degrees C for 12 h produced indolizino[1,2-b]quinolin-9(11H)-one (6a), the parent ABCD ring core of camptothecin, in essentially quantitative yield.
Dai
Weixiang
W
C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia 26506-6045, USA.
Petersen
Jeffrey L
JL
Wang
Kung K
KK
D002166:Camptothecin / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D009570:Nitriles / Q000737:chemistry*
D009570:Nitriles; D002166:Camptothecin