Total synthesis of chloptosin, a potent apoptosis-inducing cyclopeptide.
A bidirectional total synthesis of chloptosin has been achieved in 16 operations (32 individual reactions) and 3% overall yield from the readily available materials. Palladium-catalyzed tryptophan synthesis, diastereoselective selenocyclization and oxidative deselenation successfully served as key steps in construction of the dimeric core amino acid. 2-Bromo-1-ethyl pyridinium tetrafluoroborate was efficiently employed in the peptide couplings with spatial encumbrance in this synthesis.
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Shun-Ming
SM
Yu
Wen-Xu
WX
Hong
Yuan
Y
Wu
Chun-Long
CL
Zhong
Zhu-Jun
ZJ
Yao
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002384:Catalysis; D045744:Cell Line, Tumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D011724:Pyridazines; C414086:chloptosin