Total synthesis and the anticancer activity of (+)-spisulosine.
The total synthesis of the anticancer agent (+)-spisulosine has been accomplished. The strategy involved a substrate-controlled aza-Claisen rearrangement to establish the erythro-configured amino-alcohol motif followed by deoxygenation to create a methyl side-chain. Subsequent Wittig olefination then permitted the construction of the carbon backbone of the target molecule. To investigate the antiproliferative effect of 1, its biological profile was examined on a panel of 6 human malignant cell lines and demonstrated the significant anticancer activity of 1 on at least five of the evaluated lines with IC50< 1 μM (MCF-7, HTC-116, Caco-2, Jurkat and HeLa).
Department of Organic Chemistry, Institute of Chemical Sciences, P.J. Šafárik University, Moyzesova 11, 040 01 Košice, Slovak Republic.
Milica
M
Fabišíková
Department of Organic Chemistry, Institute of Chemical Sciences, P.J. Šafárik University, Moyzesova 11, 040 01 Košice, Slovak Republic. Electronic address: miroslava.martinkova@upjs.sk.
Miroslava
M
Martinková
Department of Organic Chemistry, Institute of Chemical Sciences, P.J. Šafárik University, Moyzesova 11, 040 01 Košice, Slovak Republic.
Simona
S
Hirková
Department of Organic Chemistry, Institute of Chemical Sciences, P.J. Šafárik University, Moyzesova 11, 040 01 Košice, Slovak Republic.
Jozef
J
Gonda
Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, SNP 1, 040 66 Košice, Slovak Republic.
Martina Bago
MB
Pilátová
Department of Pharmacology, Faculty of Medicine, P.J. Šafárik University, SNP 1, 040 66 Košice, Slovak Republic.
Gabriela
G
Gönciová
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D015394:Molecular Structure
D000970:Antineoplastic Agents; D008055:Lipids; C408363:spisulosine
1-deoxysphingoid bases; Antiproliferative activity; Spisulosine; Stereoselective synthesis; [3,3]-heterosigmatropic rearrangement