Antineoplastic agents. 550. Synthesis of 10b(s)-epipancratistatin from (+)-narciclasine.
By means of a five-step reaction sequence, narciclasine (2a), isolated from Narcissus sp., was converted to 10b(S)-epipancratistatin (3a) in 5.7% overall yield. The key step entailed a radical-initiated 10b,1 C-O cleavage employing tributyltin hydride to yield a B/C cis ring juncture (3b). Biological evaluation of 10b(S)-epipancratistatin (3a) provided evidence that antineoplastic activity was reduced by a factor of 10 when the B/C trans juncture was replaced with a B/C cis ring juncture.
Pettit
George R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, P.O. Box 872404, Tempe, AZ 85287-2404, USA. bpettit@asu.edu
Melody
Noeleen
N
Herald
Delbert L
DL
Knight
John C
JC
Chapuis
Jean-Charles
JC
D047151:Amaryllidaceae Alkaloids / Q000737:chemistry* / Q000302:isolation & purification; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D031427:Narcissus / Q000737:chemistry; D010617:Phenanthridines / Q000737:chemistry* / Q000302:isolation & purification; D010946:Plants, Medicinal / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C519137:10b(s)-epipancratistatin; D047151:Amaryllidaceae Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D010617:Phenanthridines; C010753:narciclasine