A fragmentation study of two compounds related to 4′‐demethylepipodophyllotoxin in negative ion electrospray ionization by MSⁿ ion‐trap time‐of‐flight mass spectrometry

Abstract

High-resolution electrospray ionization multistage tandem mass spectrometry (MS 1-7) in negative ion mode was used to determine the accurate masses and fragmentation pathways of two compounds, 4'-demethylepipodophyllotoxin and 4'-demethyl-4-azido-4-deoxyepipodophyllotoxin, which are key intermediate compounds for the preparation of podophyllotoxin-type anti-cancer drugs. The deprotonated molecules [M-H]* of both compounds were readily observed in the conventional single-stage mass spectra due to the presence of the phenolic hydroxyl group in the molecules. Abundant information on the product ions was obtained from tandem mass spectra (MS 2-7) in negative ion mode. Based on the exact masses acquired from 14 different tandem mass spectra, a similar MSn fragmentation pathway was proposed for both compounds. A characteristic product ion produced in the MS 2-4 product ion scan experiments is the cyclohexylenetrione anion [M-H-2Me-RH]* or [M-H-RH-2Me]* at m/z 351 (C19H11O7) formed by the consecutive losses of two CH3 radicals at the 3'- and 5'-positions and the neutral loss of RH, where R = a 4-substituted group (-OH or -N3), from the [M-H]* ion. This anion may be considered as diagnostic for the presence of this type of compound. The other common cleavages are the neutral losses of CO at least two times in the MS 6,7 product ion spectra. The results of this work could serve as an effective tool for the detection or determination of other derivatives of 4'-demethyl-4beta-substituted podophyllotoxin, which are widely used as intermediates for the preparation of anti-tumor drugs.

Rapid identification of lichen compounds based on the structure–fragmentation relationship using ESI-MS/MS analysis

“…The [M À H] À ion of compound 8 at m/z 417 yielded a fragment ion at m/z 225 which resulted again from the cleavage of the ester bond while ring A cleaved as a neutral molecule. 20,21 Along with the loss of the CH 3 radical, a product ion at m/z 296 was also observed due to the loss of C 5 H 11 from the m/z 367 peak. Another product ion at m/z 209, corresponding to [M À H À C 11 H 12 O 4 ] À , was observed which further decarboxylated and yielded a fragment ion at m/z 165.…”

“…APCI-MS/MS spectra of ethyl haematomate (4) have been reported, however no fragmentation patterns were given. 20,21 The CID-MS/MS spectra and proposed mechanistic fragmentation pathway of sekikaic acid (8) are shown in Fig. 4.…”

A fragmentation study on four C19-diterpenoid alkaloids by electrospray ionization ion-trap time-of-flight tandem mass spectrometry

“…Many articles tended to the positions at C (15) or C(7) [18,19]. In this paper, the position C(7) was proposed so that the fragments could lose its C(16)-methoxyl moiety to form a double bond between C(15) and C (16) positions and after that ketone -enol tautomerism occurred to form a carbonyl at C(15) position. In MS 2 analysis, the [M þ H -AcOH -MeOH -CO] þ (1d) ion from aconitine (1) was obtained that could demonstrate the above-mentioned conjecture.…”

“…The high intensity ions 1b, 1d, 2b, 3b, 3c, and 4d were all come from the loss of C(8) or C(16)-moiety. The discussions indicated that C(8) was the most active position and the activity of C(16) is slightly inferior in MS n experiments, the eliminations of moieties at C(8) and C (16) positions were the originations to generate base peak ions.…”

“…To our knowledge, there are no systematic reports about the high-resolution MS n fragmentation rules of the four compounds. In this paper, the LC/MS-IT-TOF mass spectrometer equipped with an electrospray ionization source linked to ion-trap and time-of-flight mass analyzers (ESI-IT-TOF) which enables fast acquisition of multistage tandem spectrometry (MS 1210 ) with high resolution [16,17] was used to investigate the fragmentation rules of compounds 1-4. It is important to use HR-ESI-IT-TOF-MS n technique to investigate the fragmentation of C 19 -diterpenoid alkaloids, which will provide useful information to understand their fragmentation behaviors.…”