1. Generation of C5-desoxy analogs of tetrahydroisoquinoline alkaloids exhibiting potent DNA alkylating ability.
- Author
-
Tanifuji R, Tsukakoshi K, Ikebukuro K, Oikawa H, and Oguri H
- Subjects
- Humans, Molecular Structure, Stereoisomerism, Alkaloids chemistry, DNA chemistry, Tetrahydroisoquinolines chemistry
- Abstract
C5-desoxy analogs of tetrahydroisoquinoline (THIQ) alkaloids were designed and synthesized as hitherto unexplored structural variants for evaluation of their DNA alkylating activities. While chemical synthesis of the C5-desoxy analogs bearing a phenolic hydroxyl group in the A-ring of the saframycins was assumed to be laborious based on semi-synthetic modifications, a chemo-enzymatic approach allowed for concise access to the analogs. The C5-desoxy analog 7 exhibited greater DNA alkylating ability with a wider tolerance for the sequence variations compared to cyanosafracin B. The C5-desoxy A-ring having a C8 phenolic hydroxyl group, and a C1 substituent in the vicinity of the C21 aminonitrile responsible for DNA alkylation, were demonstrated to play pivotal roles in the interaction between the THIQ alkaloids and DNA., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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