177958-20-2

Upstream product

• 171599-25-0 8-O-(dimethylcarbamoyl)DUMB2 
• 177958-19-9 8-O-tert-butyldimethylsilyl-3-methoxycarbonyl-2-methylduocarmycin B₂ 
• 153925-97-4 3-methoxycarbonyl-2-methylduocarmycin A 
• 124-40-3 dimethyl amine 
• 205652-14-8 (S)-8-Bromomethyl-4-hydroxy-2-methyl-6-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-3,6,7,8-tetrahydro-pyrrolo[3,2-e]indole-1-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Wagner-Meerwein rearrangement of duocarmycins

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 lb Rase 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.

Synthesis and antitumor activity of duocarmycin derivatives: Modification of segment A of duocarmycin B2

Several A-ring pyrrole derivatives of duocarmycin B2 were synthesized effectively from the 3-hydroxy compounds by utilizing an interesting acid- catalyzed rearrangement, their anticellular activity was preliminarily evaluated by assays of growth inhibition of HeLa S3 cells (in vitro) and antitumor activity against murine sarcoma 180 (in vivo). The 8-O-N,N- dialkylcarbamoyl derivatives of the A-ring pyrrole compound showed remarkably potent in vivo antitumor activity, superior to that of duocarmycin B2. These derivatives were subjected to further biological evaluation. They exhibited potent antitumor activity toward murine solid tumors including M5076 sarcoma, B-16 melanoma and Colon 26 adenocarcinoma. Their most noteworthy feature was their efficacy against various human xenografts including LC-6 (lung), St-4 (stomach), and Co-3 (colon).