Synthesis of all low-energy stereoisomers of the tris(pyrrolidinoindoline) alkaloid hodgkinsine and preliminary assessment of their antinociceptive activity.
The previously unknown stereoisomers 3, 4, ent-1, and ent-4 of the tris(pyrrolidinoindoline) alkaloids hodgkinsine (1) and hodgkinsine B (2) were prepared by stereocontrolled total synthesis. In each synthesis, a catalyst-controlled intramolecular Heck reaction was the key step in appending a third cis-pyrrolidinoindoline ring to a hexacyclic chimonanthine precursor. Results of the preliminary evaluation of these hodgkinsine stereoisomers in the tail flick and capsaicin pain models are reported.
Kodanko
Jeremy J
JJ
Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, USA.
Hiebert
Sheldon
S
Peterson
Emily A
EA
Sung
Leonard
L
Overman
Larry E
LE
de Moura Linck
Viviane
V
Goerck
Greice Catrine
GC
Amador
Tânia Alves
TA
Leal
Mirna Bainy
MB
Elisabetsky
Elaine
E
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D015394:Molecular Structure; D010146:Pain / Q000188:drug therapy; D013237:Stereoisomerism; D013816:Thermodynamics
D000470:Alkaloids; D018712:Analgesics, Non-Narcotic; D007211:Indoles; C077369:hodgkinsine