A novel and practical synthesis of CAT3: a phenanthroindolizidine alkaloid with potential in treating glioblastoma. Issue 51 (17th August 2018)

• Record Type: Journal Article
• Authors: Wang, Ru-Bing; Lv, Hai-Ning; Zhu, Shan-Shan; Ren, Xiao-Dong; Xu, Song; Ma, Shuang-Gang; Liu, Yun-Bao; Qu, Jing; Yu, Shi-Shan
• Is Part Of: RSC advances. Volume 8:Issue 51(2018)
• Page Start: 29301
• Page End: 29308
• Publication Date: 2018-08-17
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c8ra04511a
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : A novel and practical synthesis forCAT3, a phenanthroindolizidine alkaloid with potential in treating glioblastoma, was achieved in 11 steps with 10% overall yield and ≥99% ee. Abstract : CAT3, one of the (+)-deoxytylophorinine-based phenanthroindolizidine alkaloids, is a promising therapeutic agent for the treatment of hedgehog (Hh)-driven glioblastoma and is currently being evaluated in preclinical studies. In this paper, a novel and practical synthetic route forCAT3 was firstly demonstrated with 10% overall yield in 11 steps and has been successfully validated for pilot-plant scale preparation. Investigation of the substitution at the 3-position of phenanthrene revealed that the electron-donating functionality can well preserve the S configuration. In particular, the excellent enantiomeric excess ofCAT3 (≥99% ee) was achieved by introducing the strongly electron-donating tert -butyldimethylsilyl (TBS) group.