Synthesis and evaluation of the cytotoxicity of apoptolidinones A and D.
Apoptolidins A-D are microbial secondary metabolites shown to be selectively cytotoxic against several cancer cell lines and noncytotoxic against normal cells. Total syntheses of apoptolidinones A and D are reported. The efficient synthetic strategy leading to the apoptolidinones features construction of the common 20-membered macrolactone by an intramolecular Suzuki reaction and stereocontrolled aldol reactions establishing the C19/C20 and C22/C23 stereocenters. In contrast to apoptolidin A, the aglycones apoptolidinone A and D were shown to be noncytotoxic when evaluated against human lung cancer cells (H292).
Department of Chemistry, Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235-1822, USA.
Victor P
VP
Ghidu
Jingqi
J
Wang
Bin
B
Wu
Qingsong
Q
Liu
Aaron
A
Jacobs
Lawrence J
LJ
Marnett
Gary A
GA
Sulikowski
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology*; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018942:Macrolides; D011753:Pyrones; C504948:apoptolidinone