Total synthesis of pancratistatin relying on the [3,3]-sigmatropic rearrangement.
A new total synthesis of the antitumor alkaloid, pancratistatin (1), has been accomplished from readily available starting materials. Claisen rearrangement of the racemic dihydropyranethylene 17 was employed to construct the A and C rings with the appropriate stereochemistry. In addition, the Ireland-Claisen rearrangement of the enantiomerically pure 9 followed by ring-closing metathesis provided the important intermediate 24, thus implying that our approach could yield the enantioselective synthesis of (+)-pancratistatin. With the appropriately functionalized cyclohexene 24, stereo- and regiocontrolled functional group interchanges, such as iodolactonization, dihydroxylations, and a cyclic sulfate elimination reaction, facilitated the production of the target natural product.
Ko
Hyojin
H
Natural Products Research Institute, College of Pharmacy, Seoul National University, 28 Yungun, Jongro, Seoul 110-460, Korea.
Kim
Eunkyung
E
Park
Jae Eun
JE
Kim
Deukjoon
D
Kim
Sanghee
S
D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents; D007546:Isoquinolines; C044997:pancratistatin