Wagner-Meerwein Rearrangement of Duocarmycins

概要

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We found that treatment of the 8-O-protected-3-hydroxy derivatives of duocarmycin B2 (DUMB2,1c) with camphorsulfonic acid (CSA) in toluene interestingly gave A-ring pyrrole analogs of DUMB2 (1c) in good yields. Their structures were unambiguously elucidated on the basis of NMR and mass spectrometry, and the mechanism was considered to be a Wagner-Meerwein type rearrangement. On the other hand, treatment of the 9-O-protected-3-hydroxy derivatives of duocarmycin B1 (1b) with CSA afforded different rearrangement products. In the case of bulky groups at the 9-O position, such as a tert-butyldimethylsilyl group, normal A-ring pyrrole analogs were obtained. Under the same condition, however, the 9-O-N, N-dimethylcarbamoyl-3-hydroxy compound of 1b gave a spiro compound, which was derived from a 1,2-shift of the methoxycarbonyl group and a bonding between the C-8 position and the C-2' position. Compounds having a protective group of medium size gave a mixture of the normal rearrangement and the spiro derivative.
公益社団法人日本薬学会の論文
1996-05-15