Differentiation of the diastereomeric synthetic precursors of isofebrifugine and febrifugine by electrospray ionization tandem mass spectrometry.
Febrifugine is an alkaloid with potent antimalarial activity isolated from Dichroa febrifuga and Hydrangea umbellate, and it exists naturally with its diastereomeric component, isofebrifugine. Here we report the differentiation of diastereomeric synthetic precursors of isofebrifugine (1, cis) and febrifugine (2, trans) and a structurally similar model diastereomeric pair without a halogen substituent (3 and 4) by electrospray ionization (ESI) tandem mass spectrometry. Compounds 1-4 contain a tert-butoxycarbonyl (BOC) substituent, and the collision-induced dissociation (CID) spectra of the [M+H](+), [M+Na](+) and [M+Li](+) ions of 1-4 include the expected product ions corresponding to the loss of C(4)H(8) (isobutene) and of C(5)H(8)O(2) (BOC-H). Loss of C(5)H(8)O(2) is dominant in cis isomers (1 and 3) and/or loss of C(4)H(8) ions is dominant in trans isomers (2 and 4). The decomposition of [M+H](+) ions shows stereoselectivity in the formation of the [M+H-(BOC-H)-C(3)H(5)OBr](+) and [M+H-(BOC-H)-C(6)H(5)CH(2)OH](+) ions. The [M+Cat](+) ions (where Cat = Na or Li) additionally show loss of NaBr and HBr from [M+Cat-(BOC-H)](+), and these product ions are constantly more abundant in cis isomers than in trans isomers. The stereoselectivity for the product ion corresponding to the loss of [(BOC-H)+C(3)H(5)OBr] from [M+H](+) ions differs from that from [M+Cat](+) ions.
National Centre for Mass Spectrometry, Indian Institute of Chemical Technology, Hyderabad 500007, India.
G S
GS
Ramanjaneyulu
N
N
Sudhakar
B Venkateswara
BV
Rao
S
S
Prabhakar
D000962:Antimalarials / Q000032:analysis / Q000737:chemistry*; D031966:Hydrangea / Q000737:chemistry; D007536:Isomerism; D015394:Molecular Structure; D010880:Piperidines / Q000032:analysis / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry; D011799:Quinazolines / Q000032:analysis / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000962:Antimalarials; D010880:Piperidines; D011799:Quinazolines; C001207:febrifugine