Ammodendrine and N-methylammodendrine enantiomers: isolation, optical rotation, and toxicity.
Ammodendrine (1) was found to occur as a mixture of enantiomers in two different collections of plants identified as Lupinus formosus. The ammodendrine fraction was reacted in a peptide coupling reaction with 9-fluorenylmethoxycarbonyl-L-alanine (Fmoc-L-Ala-OH) to give diastereomers, which were separated by preparative HPLC. The pure D- and L-ammodendrine enantiomers were then obtained by Edman degradation. Optical rotation measurements revealed that the D- and L-enantiomers had optical rotations of [alpha]24D +5.4 and -5.7, respectively. D- and L-N-methylammodendrine enantiomers were synthesized from the corresponding ammodendrine enantiomers, and their optical rotations established as [alpha]23D +62.4 and -59.0, respectively. A mouse bioassay was used to determine the difference in toxicity between these two pairs of naturally occurring enantiomers. The LD50 of (+)-D-ammodendrine in mice was determined to be 94.1 +/- 7 mg/kg and that of (-)-L-ammodendrine as 115.0 +/- 7 mg/kg. The LD50 of (+)-D-N-methylammodendrine in mice was estimated to be 56.3 mg/kg, while that of (-)-L-N-methylammodendrine was determined to be 63.4 +/- 5 mg/kg. These results establish the rotation values for pure ammodendrine and N-methylammodendrine and indicate that there is little difference in acute murine toxicity between the respective enantiomers.
Lee
Stephen T
ST
Poisonous Plant Research Laboratory, Agricultural Research Service, United States Department of Agriculture, 1150 East, 1400 North, Logan, Utah 84341, USA. stlee@cc.usu.edu
Molyneux
Russell J
RJ
Panter
Kip E
KE
Chang
Cheng-Wei Tom
CW
Gardner
Dale R
DR
Pfister
James A
JA
Garrossian
Massoud
M
D000818:Animals; D002417:Cattle; D002418:Cattle Diseases; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity; D004195:Disease Models, Animal; D031297:Lupinus / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity; D010945:Plants, Edible; D011725:Pyridines / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity; D013237:Stereoisomerism
D004095:Dihydropyridines; C114432:N-methylammodendrine; D010880:Piperidines; D011725:Pyridines; C068578:ammodendrine