Utilisation of electrospray time-of-flight mass spectrometry for solving complex fragmentation patterns: application to benzoxazinone derivatives

In this paper we describe the application of electrospray time-of-flight mass spectrometry (ESI-TOFMS) to structural elucidation of the fragment ions formed from a range of natural and synthetic allelochemical derivatives. The extensive mass spectrometric characterisation of ten non-glucosylated benzoxazinone derivatives using this method is described here for the first time. The analytes include six naturally occurring 1,4-benzoxazin-3(4H)-one derivatives, including the hydroxamic acids DIMBOA [2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one] and DIBOA [2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one], lactams HBOA [2-hydroxy-2H-1,4-benzoxazin-3(4H)-one] and HMBOA [2-hydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one], benzoxazolinones BOA [benzoxazolin-2(3H)-one] and MBOA [6-methoxy-benzoxazolin-2(3H)-one] and four synthetic variations, 2'H-DIBOA [4-hydroxy-2H-1,4-benzoxazin-3(4H)-one], 2'OMe-DIBOA [2-methoxy-4-hydroxy-2H-1,4-benzoxazin-3(4H)-one], 2'H-HBOA [2H-1,4-benzoxazin-3(4H)-one] and 2'OMe-HBOA [2-methoxy-2H-1,4-benzoxazin-3(4H)-one]. Assignments of the mass spectral fragments were aided by elemental composition calculation results, comparison of structural analogues and background literature, and acquired knowledge regarding feasible structures for the compounds. The influence of substituents on the chemical reactivity of the compounds with respect to the observed MS behaviour over varying nozzle potentials is addressed and, through comparison of the structural analogues, generic fragmentation patterns have also been identified.     

Guaiane-type sesquiterpenoid glucosides from Gardenia jasminoides Ellis

Two new guaiane-type sesquiterpenoid glucosides (1 and 2) were isolated from the fruit of Gardenia jasminoides Ellis. Their structures were elucidated to be (1R,7R,10S)-11-O-β-D-glucopyranosyl-4-guaien-3-one (1) and (1R,7R,10S)-7-hydroxy-11-O-β-D-glucopyranosyl-4-guaien-3-one (2) by one- and two-dimensional NMR techniques ((1)H NMR, (13)C NMR, HSQC, HMBC and NOESY), MS, CD spectrometry and chemical methods.     

Enantiomeric separation of close analogs to naturally occurring 1,4-benzoxazin-3-ones by liquid chromatography using β-cyclodextrin-modified stationary phase

Summary A liquid chromatographic procedure on a 5 m LiChroCART column using chemically bonded -cyclodextrin (ChiraDex) as chiral selector was developed for the enantiomeric separation of four 2H-1,4-benzoxazin-3(4H)-ones which are close analogs of the cyclic hydroxamic acids 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA) and 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3 (4H)-one (DIMBOA) naturally occurring inGramineae species.     

Condensation of Ethyl 2-Oxoindoline-3-glyoxylate with o-Aminophenol and o-Phenylenediamine

A method is presented for the synthesis of 3-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)-1,4-dihydroquinoxalin-2-one and 2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2H-1,4-benzoxazin-3(4H)-one by the reaction of ethyl 2-oxoindoline-2-glyoxylate with o-aminophenol and o-phenylenediamine. Proposed reaction mechanisms are presented.     

Preparative isolation and purification of two benzoxazinoid glucosides from Acanthus ilicifolius L. by high-speed counter-current chromatography

The first preparative separation of two benzoxazinoids, (2R)-2-O-beta-d-glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one (HBOA-Glc) and (2R)-2-O-beta-d-glucopyranosyl-4-hydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA-Glc), by means of high-speed counter-current chromatography (HSCCC) from the n-butanol extract of Acanthus ilicifolius L. is presented. The two-phase solvent system containing ethyl acetate-n-butanol-0.5%NH(4)OH (2:3:5, v/v/v, system B) was selected for the one-step HSCCC separation of HBOA-Glc and DIBOA-Glc according to the partition coefficient values (K) for target compounds and the separation factor (alpha) between the two target compounds. In the one-step HSCCC separation using solvent B, from 100mg n-butanol extract of A. ilicifolius, 6.3 mg HBOA-Glc and 6.8 mg DIBOA-Glc were isolated with purities of 90.3% and 80.2%, respectively. In order to obtain the two target compounds with higher purity, a second separation process was developed comprising two steps. In the two-step separation, the sample was first pre-purified by HSCCC using ethyl acetate-n-butanol-water (2:3:5, v/v/v, system A) solvent system and then purified using solvent system B. A 100-mg amount of the n-butanol extracts of A. ilicifolius was separated to yield 5.8 mg of HBOA-Glc and 4.8 mg of DIBOA-Glc with purities of 97.1% and 94.8%, respectively, which were directly used for NMR analyses.     

Biomimetic synthesis of 4-acetylbenzoxazolin-2(3H)-one isolated from Zea mays

4-Acetylbenzoxazolin-2(3H)-one has been prepared biomimetically during attempts to synthesize the hemiacetalic hydroxamic acid 5-acetyl-2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one by the immediate degradation of this unstable compound generated as an intermediate. Thus, 4-acetylbenzoxazolin-2(3H)-one recently isolated from Zea mays kernels, and similar to other benzoxazolin-2(3H)-ones known from plant sources, is assumed to have originated from the degradation of natural 5-acetyl-2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one which in turn could have been enzymatically released by a β-glucosidase from the corresponding 2-β-D-glucoside.     

Ardisimamillosides C-F, four new triterpenoid saponins from Ardisia mamillata

Four new triterpenoid saponins, ardisimamilloside C (1), 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->4)-[beta -D-glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl]-3beta,16al pha,28,30-tetrahydroxy-olean-12-en, ardisimamilloside D (2), 3-O-?alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->4)-[beta -D-glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl]-3beta,15al pha,28,30-tetrahydroxy-olean-12-en, ardisimamilloside E (3), 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->4)-[beta -D-glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosl]-13beta,2 8-epoxy-3beta,16alpha,29-oleananetriol, and ardisimamilloside F (4), 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->4)-[beta -D-glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl]-3beta,16al pha-dihydroxy-13beta,28-epoxy-oleanan-30-oic acid were isolated from the roots of Ardisia mamillata Hance. Structure assignments were established on the basis of highresolution (HR)-FAB-MS, 1H-, 13C-, and two-dimensional (2D)-NMR spectra, and on the chemical evidence.     

Conformationally tailored N-[(2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl)carbonyl]proline templates as molecular tools for the design of peptidomimetics. Design and synthesis of fibrinogen receptor antagonists

The proline peptide bond was shown by 2D proton NMR studies to exist exclusively in the trans conformation in benzyl (2S)-1-[[(2S)-2-methyl-6-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl]-2-pyrrolidinecarboxylate [(S,S)-11], benzyl (2S)-1-[[(2S)-2-methyl-7-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl]-2-pyrrolidinecarboxylate [(S,S)-9], and in the corresponding 6-amino and 7-amino carboxylic acids (S,S)-3 and (S,S)-4. On the other hand, the diastereomers (R,S)-11 and (R,S)-9 containing an (R)[2-methyl-6/7-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl moiety, and the diastereoisomers (R,S)-3 and (R,S)-4 incorporating an (R)[6/7-amino-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl moiety were found to exist as equilibria of trans(63-83%) and cis(17-37%) isomers. These conformationally defined templates were applied in the construction of RGD mimetics possessing antagonistic activity at the platelet fibrinogen receptor.     

2-Aryl-4H-3,1-benzoxazin-4-ones nitration

2-(3-Nitrophenyl)-4H-3,1-benzoxazin-4-one is formed in the nitration of 2-phenyl-4H-3,1-benzoxazin-4-one, while 2-(2-tosylamino-5-nitrophenyl)-4H-3,1-benzoxazin-4-one is formed in the nitration of 2-(2-tosylaminophenyl)-4H-3,1-benzoxazin-4-one.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 908–909, July, 1974.     

Reaction of 4-acetoxy-1,4-benzoxazin-3-one with DNA. A possible chemical mechanism for the antifungal and mutagenic activities

A reaction of 4-acetoxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one with DNA and nucleotides was described. The N⁴ position of the benzoxazinone reacted with the C₈ position of the guanine residue of DNA and guanylic acid.     

Steroid glycosides of the leaves of Yucca aloifolia

Two new steroid glycosides have been isolated from the leaves of aloe yucca and their structures have been established. Glycosides B and C are tigogenin penta-and hexaosides. Glycoside B, which we have called yuccaloeside B is (25R)-5α-spirostan-3β-ol 3-{[O-β-D-glucopyranosyl-(1→2)]-[O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside}, and glycoside C, which we have called yuccaloeside C is (25R)-5α-spirostan-3β-ol 3-{[(O-β-D-glucopyranosyl-(1→3)-O-β-D-glucopyranosyl-(1→2)]-[O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside}.     

Reaction of Hetareno[e]pyrrolediones with 1,3-C,N-Binucleophiles. Isolation of Intermediate Product of Spiro Heterocyclization

Russian Journal of Organic Chemistry - Ethyl 1,2,4-trioxo-2,4-dihydro-1H-pyrrolo[2,1-c][1,4]benzoxazine-3-carboxylates reacted with ethyl (2Z)-[2-oxo-2H-1,4-benzoxazin-3(4H)-ylidene]acetates to...     

Two New Steroidal Glycosides from Ophiopogon japonicus

The tuber of Ophiopogon japonicus Ker-Gawl. is recorded to have various functions, such as against cardiovascular diseases and anti-bacteria, and used as a potent drug to treat different diseases, especially heart diseases1. Since the first steriodal glycoside was isolated from the plant by Japanese scholars2, much attention has been paid to the studies of the chemical components of O. japonicus in recent decades. Steroidal glycosides as the major glycosides with the aglycones of ruscogenin …     

珠子参化学成分分析

从珠子参根茎中分离得到7个化合物. 利用核磁共振、 质谱和红外等手段, 并结合其理化性质, 鉴定了其结构, 它们分别是24(R)-珠子参苷R1, 6-O-[β-D-吡喃葡萄糖基(1→2)-β-D-吡喃葡萄糖基]-20-O-[β-D-吡喃葡萄糖基(1→4)-β-D-吡喃葡萄糖基]-20(S)-原人参三醇、 6″-乙酰基-人参皂苷Rd、 人参皂苷Rf、 竹节参皂苷Ⅳa、 人参皂苷Rd和竹节参皂苷Ⅴ. 其中, 24(R)-珠子参苷R1和6-O-[β-D-吡喃葡萄糖基(1→2)-β-D-吡喃葡萄糖基]-20-O-[β-D-吡喃葡萄糖基(1→4)-β-D-吡喃葡萄糖基]-20(S)-原人参三醇为2个新化合物, 6″-乙酰基-人参皂苷Rd 和人参皂苷Rf为首次从珠子参根茎中得到.     

A convenient synthesis of 3,4-dihydro-1,4-benzoxazin-2-ones

3,4-Dihydro-1,4-benzoxazin-2-one was prepared for the first time by catalytic hydrogenation of 4-benzyl-3,4-dihydro-1,4-benzoxazin-2-one. A simple and efficient synthesis of 4-benzyl- and 4-alkyl-3,4-dihydro-1,4-benzoxazin-2-one derivatives from ethyl 2-(2-hydroxyphenylamino)acetate and aldehydes is described. Some considerations regarding the reactivity of 3,4-dihydro-1,4-benzoxazin-2-ones are given.     

Rearrangement of 1,4-benzodiazepin-2,4-diones to 3,l-benzoxazin-4-ones

Treatment of 7-chloro-3,4-dihydro-1H-1,4-benzodiazepin-2,5-dione (Ia) with refluxing acetic anhydride in the presence of pyridine afforded 6-chloro-2-methyl-4H-3,1-benzoxazin-4-one (IIa). A plausible reaction path for this novel rearrangement reaction is described: Ia → 4-acetyl-7-chloro-3,4-dihydro-lH-1,4-benzodiazepin-2,5-dione → 7-chloro-1,4-diacetyl-3,4-dihydro-lH-1,4-benzodiazepin-2,4-dione → IIa. When 7-chloro-3,4-dihydro-4-methyl-lH-1,4-benzodiazepin-2,5-dione (Ib), 3,4-dihydro-4-methyl-1H-1,4-benzodiazepin-2,5-dione (Id) and 3,4-dihydro-1-methyl-1H-1,4-benzodiazepin-2,5-dione (Ie) were allowed to react with acetic anhydride under conditions similar to those used for the rearrangement reaction, only acetylation occurred.     

Syntheses for 2-amino and 2-mercapto-2H-1,4-benzoxazin-3(4H)-one and 2H-1,4-benzothiazin-3(4H)-one as aza and thio analogues of the natural product blepharigenin

2-Amino-2H-1,4-benzoxazin-3(4H)-one 3 , 2-amino-2H-1,4-benzothiazin-3(4H)-one 4 , 2-mercapto-2H-1,4-benzoxazin-3(4H)-one 7 , and 2-mercapto-2H-1,4-benzothiazin-3(4H)-one 8 representing aza and thio analogues of the natural product's aglucone Blepharigenin (2-hydroxy-2H-1,4-benzoxazin-3(4H)-one) from Gramineae and Acantnaceae species have been synthesized for the first time from their 2-bromo precursors 1 and 2 . Attempts to similarly prepare the 4-hydroxy derivatives of 7 and 8 , which would represent new thio analogues of the naturally occurring cyclic hydroxamic acid, 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one, have failed.     

Reaction of anthranilic acid and methoxy- and nitro-substituted anthranilic acid with p-toluenesulfonyl chloride in pyridine

The reaction of anthranilic acid and methoxy- and nitro-substituted anthranilic acid with p-toluenesulfonyl chloride in pyridine was investigated. Anthranilic acid and its methoxy-substituted derivatives react to give the corresponding 2-(2-tosylaminophenyl)-4H-3,1-benzoxazin-4-ones and N,N'-ditosyldianthranilides. At 20°C, 4-nitroanthranilic acid gives primarily 2-(2-amino-4-nitrophenyl)-7-nitro-4H-3,1-benzoxazin-4-one, while its tosyl derivative is obtained at 114°. The products of the reaction of 5-nitroanthranilic acid with p-toluenesulfonyl chloride are 2-nitro-11H-pyrido[2,1-b]quinazolin-11-one and 2-(2-amino-5-nitrophenyl)-6-nitro-4H-3, 1-benzoxazin-4-one. The yield of benzoxazinone generally increases as the temperature is raised.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1341–1344, October, 1972     

A new steroidal glycoside from the Ophiopogon japonicus Ker-Gawler (Liliaceae)

A new steroidal glycoside (1), (25R)-14α, 17α-hydroxyspirost-5-en-3β-yl 3-O-α-L-rhamnpyranosyl-(1 → 2)-β-D-glucopyranosyl-(1 → 3)-β-D-glucopyranoside, together with three known steroidal glycosides, (25R)-3β-hydroxyspirost-5-en-1β-yl-3-O-α-L-rhamnopyranosyl-(1 → 2)-O-β-D-xylopyranosyl-(1 → 3)-α-L-arabinopyranoside (2), Cixi-ophiopogon B (3) and Cixi-ophiopogon A (4), were obtained from the tuberous roots of Ophiopogon japonicus (Liliaceae). Compound 2 was isolated from the Ophiopogon genus for the first time. Their structures were identified on the basis of extensive mass and nuclear magnetic resonance spectroscopic analysis.     

2-Carbethoxy-4H-3,1-benzoxazin-4-one. 2. Hydrazinolysis

3-Amino-2-carboxymethylquinazolin-4(3H)-one was obtained by hydrazinolysis of 2-carbethoxymethyl-4H-3,1-benzoxazin-4-one. Its transformations into 2-hydroxypyrazolo[5,1-b]quinazolin-9(1H)-oneand3-amino-2-hydrazido-(orbenzylamido)carbonylmethylquinazoline-4(3H)-ones were studied.For Communication 1, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1128–1130, August, 1991.