Meisenheimer rearrangement of azetopyridoindoles, VI. Synthesis of 12-carbaeudistomin and related compounds.
For structure-activity relationship investigation of eudistomins 1, 12-carbaeudistomin 3, its 1,10-trans isomer 4, and 11,12-didehydro-12-carbaeudistomin 5 have been synthesized. The [2,3]-Meisenheimer rearrangement of the corresponding N-oxide of the 2-vinylazetopyridoindole 12a bearing a benzenesulfonyl group as a protective group of the indole nitrogen atom afforded the oxazepino ester 14, which was easily isomerized to 20a. Compounds 3 and 4 were synthesized from 14 and 20a, respectively, according to the following reaction sequences [hydrogenation of the double bond (Pd-C/H2), desulfonylation (Mg in MeOH), hydrolysis (AlBr3-EtSH), and Curtius rearrangement (a mixed anhydride method using NaN3), followed by debenzylation (Pd-C/H2)]. The Curtius reaction of the carboxylic acid 27 using DPPA gave the carbamate 29, which was subjected to debenzylation (AlBr3-EtSH) followed by desulfonylation (LiAlH4) to afford 5. Evaluation of anti-influenza virus activities of the amino compounds 3, 4, and 5 revealed that 12-carbaeudistomin 3 possesses a specific activity against influenza virus B.
Kurihara
T
T
Osaka University of Pharmaceutical Sciences, Japan.
Sakamoto
Y
Y
Matsumoto
H
H
Kawabata
N
N
Harusawa
S
S
Yoneda
R
R
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002243:Carbolines / Q000138:chemical synthesis* / Q000494:pharmacology; D009980:Influenza A virus / Q000187:drug effects; D009981:Influenza B virus / Q000187:drug effects
C087387:12-carbaeudistomin; D000998:Antiviral Agents; D002243:Carbolines