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© 2006 American Society for Nutrition J. Nutr. 136:726S-731S, March 2006

Supplement: Significance of Garlic and Its Constituents in Cancer and Cardiovascular Disease

Tetrahydro-ß-Carboline Derivatives in Aged Garlic Extract Show Antioxidant Properties1,2

Makoto Ichikawa*,{dagger},3, Jiro Yoshida*, Nagatoshi Ide*, Takashi Sasaoka*, Hiroyuki Yamaguchi* and Kazuhisa Ono{dagger}

* Healthcare Research Institute, Wakunaga Pharmaceutical Co., Ltd., Hiroshima 739-1195, Japan and {dagger} Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Hiroshima 739–8530, Japan

3 To whom correspondence should be addressed. E-mail: ichikawa_m{at}wakunaga.co.jp.


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 LITERATURE CITED
 
This study used the hydroden peroxide scavenging assay to investigate antioxidant chemical constituents derived and separated from aged garlic extract, a unique garlic extract produced by soaking sliced garlic in an aqueous ethanol solution for >10 mo. Four types of 1, 2, 3, 4-tetrahydro-ß-carboline derivatives (THßCs); 1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid, and 1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid (MTCdiC), from both diastereoisomers, were isolated and identified by use of liquid chromatography–mass spectrometry. All these compounds indicate strong hydrogen peroxide scavenging activities and inhibit 2, 2'-azobis(2-amidinopropane) hydrochloride–induced lipid peroxidation. Particularly, (1S, 3S)-MTCdiC had the most potent hydrogen peroxide scavenging activity, more than ascorbic acid. The (1R, 3S)- and (1S, 3S)-MTCdiC at 50–100 µmol/L and 10–100 µmol/L inhibited LPS-induced nitrite production. Interestingly, THßCs were not detected in raw garlic and other processed garlic preparations, but they were generated and increased during the natural aging garlic extraction process. These data suggest that THßCs, which are formed during the natural aging process, are potent antioxidants in aged garlic extract and thus may be useful for the prevention of diseases associated with oxidative damage.

KEY WORDS: • aged garlic extract • tetrahydro-ß-carboline derivatives • Maillard reaction products • antioxidant • liquid chromatography mass spectrometry

Formation of 1,2,3,4-tetrahydro-ß-carboline derivatives (THßCs)4 occurs via a Pictet-Spengler condensation of tryptophan with aldehydes or {alpha}-oxo acids (1). These compounds are naturally occurring substances chemically produced during food production, storage, and processing. THßCs have been identified in soy sauces, beers, wines, chocolate, and cocoa (2–5). These alkaloids have been demonstrated to exhibit antioxidant properties (6,7) and to inhibit platelet aggregation (2), monoamine oxidase, monoamine uptake, and binding to benzodiazepine receptor (8,9).

Garlic (Allium sativum) has long been used universally as a flavoring ingredient, functional food, and traditional medicine. It has been believed that the medical and beneficial properties may be attributed to specific constituents found in garlic and its extracts, and many studies suggest that organosulfur compounds are responsible for the biologic activities (10). Aged garlic extract (AGE) is manufactured by a unique but natural long-term process called the aging extraction process, which takes >10 mo at room temperature. AGE contains unique organosulfur compounds, including S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC). AGE and its constituents, SAC and SAMC, have been reported to show a variety of biologic activities, including antioxidant function (11–13), cancer prevention (14), antiatherogenic (15), and antiplatelet aggregation activity (16,17). To analyze and identify the antioxidant compounds, AGE was separated into the various fractions, and their activities were evaluated by the hydrogen peroxide scavenging assay. Four alkaloids from both diastereoisomers of THßCs; 1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acids (MTCC); and 1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid (MTCdiC) were found in AGE by liquid chromatography mass spectrometry (LC-MS) and collision-induced dissociation (CID). We further determined the antioxidant effects of these compounds by use of in-vitro assay systems, and also analyzed the changes in concentrations of the alkaloids using LC-MS during the natural long-term extraction process of garlic.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 LITERATURE CITED
 
    AGE. AGE was manufactured under a license from the Ministry of Health and Welfare of Japan and formulated as follows: sliced garlic cloves were soaked in an aqueous ethanol solution and extracted for >10 mo at room temperature (11), in compliance with the US Pharmacopeia/NF Garlic Fluidextract monograph (18). AGE used in these experiments contained SAC in the range of 1.6–2.4 mg/g dry wt (19).

    Chemicals. Linoleic acid, AAPH, LPS, acetonitrile, hydrochloric acid (HCl), sodium chloride (NaCl), chloroform (CHCl3), and trifluoroacetic acid (TFA) were purchased from Wako Pure Chemical Industries. Methanol (MeOH) was obtained from Yoneyama Yakuhin Kogyo. Horseradish peroxidase and 2, 2'-azino-di-[3-ethyl-benzthiazoline-6-sulfonic acid] (ABTS) were purchased from Boehringer Mannheim Japan.

    Preparation of AGE fractions. AGE was separated into the various fractionations according to the method reported by Ryu et al. (20). AGE (450 g) was partitioned between ethyl acetate and water. The water layer (AGE-P, 448 g) was dialyzed against distilled water by use of Spectra/Por membrane MWCO: 1,000 (Spectrum) at 4°C for 3 d to give fraction-1 (F-1, <1,000, 400 g) and fraction-2 (F-2, >1,000, 50 g). F-2 underwent chromatography on DEAE Toyopeal 650M (Tosoh) with 0.05 mol/L Tris-HCl buffer (pH 8.0) and 0.05 mol/L Tris-HCl buffer (pH 8.0) containing 2 mol/L NaCl to give fraction-3 (F-3; sugars, 42 g) and fraction-4 (F-4; proteins, 8 g). F-1 was subjected to reversed-phase column chromatography on MCI gel CHP20P (Mitsubishi Chemical) with stepwise gradient elution (water, 10% MeOH, 50% MeOH to MeOH) to give 4 fractions: water (F-1A, 380 g), 10% MeOH (F-1B, 0.6 g), 50% MeOH (F-1C, 1.5 g), and MeOH (F-1D, 0.5 g). F1-D elute was further fractionated on Silica gel eluting with CHCl3 followed by gradient mixtures of CHCl3-MeOH and MeOH, and given subfractions were subjected to the preparative HPLC by use of MeOH:water (1:9, v:v) as eluent.

    Mass spectrometric analysis of THßCs. Chromatographic separation for LC-MS was performed on a Capcell Pak C18UG120 (75 mm x 2.0 mm i.d., Shiseido). Gradient elution was performed by use of HP-1100 binary pump (Agilent). Solvent A was 0.05% TFA in water, solvent B was 0.05% TFA in water:acetonitrile (1:1, v:v), and the linear gradient was programmed as follows: 0 min, 20% solvent B; 20 min, 60% solvent B; 30 min, 100% solvent B. The flow rate was 0.2 mL/min. The detector was an ion-trap mass spectrometer LCQ (Thermoelectron) equipped with atmospheric pressure chemical ionization (APCI). An optimal condition of the APCI source parameter was obtained at the following values: sheath gas flow rate, 60 (arbitrary unit); vaporizer temperature, 450°C; discharge current, 5 µA; capillary voltage, 3 V; capillary temperature, 150°C; scanning mode, positive; scan range, m/z 100–300. CID analysis was performed in the trap with helium, and the relative collision energy was set at 35%.

    Nuclear magnetic resonance spectroscopy (NMR). 1H- and 13C-NMR and NOE experiments were performed on a JNM-ECP500 (JEOL) apparatus at 500 MHz and 125 MHz, respectively.

    Synthesis of reference compounds. Synthesis of THßCs was conducted according to the methods described previously (4,21).

    Hydrogen peroxide scavenging assay. The scavenging effects of obtained fractions or THßCs identified in AGE on hydrogen peroxide were determined according to the method of Okamoto et al. (22), with slight modifications. Briefly, 10 µL of 500 µmol/L hydrogen peroxide, 10 µL of sample or water as a control, 40 µL of 150 U/mL horseradish peroxidase, and 40 µL of 0.1% ABTS were added to 120 µL of 0.1 mol/L phosphate buffer (pH 6.0). The solution was then incubated at 37°C for 15 min. Absorbance at 414 nm was measured using Multiskan Ascent (Labsystems).

    AAPH-induced lipid peroxidation. AAPH is an azo compound, which works as a radical initiator and causes lipid peroxidation. The effects of THßCs on AAPH-induced lipid peroxidation were determined according to the method described previously (23,24).

    Determination of nitrite production from macrophages. The effects of THßCs on nitrite production from macrophages were determined according to the methods described previously (13,25).

    Preparation of processed garlic and analysis. The various processed garlic samples were prepared by the methods described below. Freeze-dried sample: the garlic cloves were frozen in liquid nitrogen and pulverized, then vacuum-dried. Sliced sample: the garlic cloves were sliced at a thickness of 1.5 mm and then freeze-dried. Baked sample: the sliced garlic cloves were baked at 180°C for 20 min and then freeze-dried. Boiled sample: the sliced garlic cloves were boiled in water (1:20, wt:v) for 20 min and then freeze-dried. Crushed sample: the garlic cloves were crushed with water (1:1, wt:v) and then freeze-dried. These processed garlic samples were extracted with 90% MeOH containing 0.01 mol/L HCl and analyzed by HPLC. HPLC conditions for alliin, isoalliin, methiin, cycloalliin, and {gamma}-L-glutamyl-S-methyl-L-cysteine were as follows: column, Shodex Asahipak NH2P-50 2D (150 mm x 2.0 mm i.d., Showa Denko); flow rate, 0.2 mL/min; mobile phase, acetonitrile:water (84:16, v:v) containing 0.2% phosphoric acid; wavelength, UV 210 nm. HPLC conditions for {gamma}-L-glutamyl-S-allyl-L-cysteine and {gamma}-L-glutamyl-S-(trans-1-propenyl)-L-cysteine were follows: column, Symmetry C18 (150 mm x 3.9 mm i.d., Waters); flow rate, 0.8 mL/min; mobile phase, 50 mM phosphate buffer (pH 2.6):MeOH (85:15, v:v); wavelength, UV 205 nm.

    Statistical analysis. Data were analyzed by use of the one-tailed Student's t test (Microsoft Excel), and results were expressed as the mean ± SE. A P value of <0.05 was considered to represent a significant difference.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 LITERATURE CITED
 
The scavenging effects of AGE and its fractions on hydrogen peroxide were investigated. AGE, AGE-P, F-1, F-2, F-3 and F-4 showed the individual scavenging activities of 75%, 59%, 66%, 55%, 0%, and 97%, respectively, at 1 g/L. According to these scavenging activities obtained and considered with the weights of each fractions, F-1 was further separated to the fractions by use of MCI gel CHP 20P with stepwise gradient elution to give F-1A to F-1D. At 0.1 g/L, F-1C and F-1D showed 100% scavenging activity against hydrogen peroxide. However, F-1, F-1A, and F-1B did not show any scavenging activities. In two bioactive fractions, F-1D was further separated by repeated column chromatography on silica gel and preparative HPLC, and as a result, 13 subfractions were obtained. These individual subfractions were analyzed by LC-MS, CID, and NMR, and expected compounds were also synthesized. Fig. 1 shows THßCs, (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid (1a), (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid (1b), (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid (2a), and (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid (2b), identified in AGE by LC-MS, CID, and NMR analytic methods. A profile of THßCs from fraction F-1D is outlined in Fig. 2 as one of the examples. The protonated molecular ions of 1a/b and 2a/b were obtained at m/z 231 and 275, respectively. Product ion at m/z 158 obtained by CID analysis of 1a/b was formed by neutral loss of the iminoacetic acid moiety due to retro-Diels-Alder fragmentation (4). Product ion spectra of 2a/b show m/z 231, 202, and 159. Product ion at m/z 231 apparently resulted from the loss of CO2 characteristic for carboxylic acid. Product ions at m/z 202 and m/z 159 were formed by the loss of the iminoacetic acid moiety and the indole moiety, respectively (4). Fig. 3 shows the changes in concentrations of THßCs during the natural aging process of garlic. All these compounds were formed from the beginning of the natural aging process, and remarkably increased between 4 and 10 mo. MTCdiCs further increased in concentrations after 10 mo of aging, whereas MTCCs reached a plateau at 10 mo. However, in raw and other processed garlic, such as sliced, baked, boiled, and crushed garlic, none of these compounds were detected (detection limit: 1a/b, 0.4 nmol/g; 2a/b, 1.8 nmol/g) (Table 1).


Figure 1
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  		FIGURE 1  1, 2, 3, 4-tetrahydro-ß-carboline derivatives identified in aged garlic extract.

 

Figure 2
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  		FIGURE 2  Liquid chromatography–atmospheric pressure chemical ionization mass spectrometry chromatogram at m/z 231 (A) and m/z 275 (B) in F1-D fraction of aged garlic extract. F-1D: methanol elute fraction from MW <1000 fraction of aged garlic extract using reversed-phase chromatography. 1a: (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid. 1b: (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid. 2a: (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid. 2b: (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid. Chromatographic conditions were performed on an Capcell Pak C18UG120 column (75 mm x 2.0 mm i.d.) by use of the linear gradient with 0.05% TFA in water (solvent A) and 0.05% TFA in water:acetonitrile (1:1, v:v, solvent B) as mobile phase. The gradient program was as follows: 0 min, 20% solvent B; 20 min, 60% solvent B; 30 min, 100% solvent B. Mass spectrometry conditions were as follows: vaporizer temperature, 450°C; discharge current, 5 µA; capillary voltage, 3 V; capillary temperature, 150°C.

 

Figure 3
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  		FIGURE 3  Changes in concentrations of MTCCs (A) and MTCdiCs (B) during the natural aging process. Samples prepared during the garlic aging process were analyzed by LC-MS. Data represent means ± SEM of repeated studies (at least 3 times).

 

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  		TABLE 1 Contents of tetrahydro-ß-carboline derivatives and organosulfur compounds in garlic and its preparations

 
The scavenging effects of THßCs on hydrogen peroxide are shown in Fig. 4. Hydrogen peroxide was scavenged at 49% or 35% by 1a or 1b at 250 µmol/L, respectively. However, scavenging activities of MTCdiCs are approximately 5 to 10 times stronger than MTCCs. In particular, 2b has shown stronger activity than ascorbic acid, a well-known common antioxidant. Fig. 5 shows the effects of THßCs on AAPH-induced lipid peroxidation. The most potent hydrogen peroxide scavenger, 2b and its monocarboxylate, 1b, were used in the lipid peroxidation experiment. This experiment used incubation of linoleic acid-SDS micelle solution with AAPH for 20 min, resulting in significant oxygen consumption and thus lipid peroxidation. In this system, coincubation with 1b or 2b inhibited AAPH-induced lipid peroxidation by approximately 30% at 1 mmol/L and 10% at 0.1 mmol/L. However, there was no difference between 1b and 2b, and the activities were not potent in comparison with BHT, another well-known antioxidant. The effects of THßCs on LPS-induced nitrite production from murine macrophages are shown in Fig. 6. Exposure of LPS to murine macrophage cell line J744.A resulted in a significant release of nitrites. Coincubation of J774. A cells with 2a or 2b resulted in a significant inhibition of nitrite release from macrophages at 50 to 100 µmol/L or 10 to 100 µmol/L, respectively, although MTCCs failed to inhibit it at 250 µmol/L.


Figure 4
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  		FIGURE 4  Scavenging effects of tetrahydro-ß-carboline derivatives identified in AGE on hydrogen peroxide. Data represent means ± SEM of triplicate samples. 1a: (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid. (B), (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid. 2a: (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid. 2b: (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid.

 

Figure 5
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  		FIGURE 5  Effects of tetrahydro-ß-carboline derivatives identified in AGE on 2, 2'-azobis(2-amidinopropane) hydrochloride-induced lipid peroxidation. Data represent means ± SEM (n = 4). 1b: (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid. 2b: (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid.

 

Figure 6
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  		FIGURE 6  Effects of tetrahydro-ß-carboline derivatives identified in AGE on LPS-induced nitrite production from murine macrophages. Data represent means ± SEM (n = 3). 1a: (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid. 1b: (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid. 2a: (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid. 2b: (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
LITERATURE CITED
 
To identify antioxidants in AGE, AGE was separated to the various fractions by repeated chromatography, and four THßCs were finally identified (Fig. 1). To our knowledge, this report is the first to describe THßCs in either raw garlic or other processed garlic preparations. Quantitative analysis of these compounds was done with LC-MS, a powerful and efficient tool for analyzing minor compounds in complicated materials. Interestingly and importantly, THßCs were not detected in raw garlic, but they were generated at the beginning of the extraction process with intrinsic natural enzymes during the long-term aging process of garlic. An especially remarkable increase was detected between 4 and 10 mo of extraction, and MTCdiCs increased further during this aging process, whereas the contents of MTCCs reached a plateau at 10 mo after the beginning of the extraction process.

It has been reported that the chemical formation of THßCs is dependent upon storage time, pH, temperature, and other processing/extraction conditions. The THßCs also found in fermented and maturated foodstuffs such as beer and wine are believed to be related to the amount of aldehydes (26–28). THßCs are chemically synthesized by condensation between tryptophan and acetaldehyde or pyruvic acid (Fig. 7). Acetaldehyde, a precursor of MTCC, is believed to come from alcohol (27,28). On the other hand, two pathways are believed to form pyruvic acid, a precursor to MTCdiC, in the natural aging process of garlic; one is the alliin-allicin pathway, which is the most common pathway in garlic, and another is via the Maillard reaction process. When raw garlic is cut or crushed, alliin, a major organosulfur compound in raw garlic, is transformed into allicin by alliinase, and pyruvic acid is formed as a by-product (29,30). In the latter process, 3-deoxyglucosone is a key compound, which is well known as a Maillard reaction product. The compound has been reported to cause C3/C3 cleavage and to form the pyruvaldehyde in atypical Maillard reaction system (31). MTCdiC may be formed by the nonenzymatic reaction with tryptophan and pyruvic acid and/or pyruvaldehyde formed in these two expected pathways. We demonstrated that THßCs were detected in AGE, but not in raw and other processed garlic such as sliced, baked, boiled, and crushed preparations. These data suggest that the natural aging process of garlic generates more THßCs than other processes or forms of garlic.


Figure 7
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  		FIGURE 7  Expected pathway to form 1, 2, 3, 4-tetrahydro-ß-carboline derivatives during the natural aging process of garlic.

 
In conclusion, THßCs identified in AGE show potent antioxidant properties in in-vitro systems. In particular, 2b is a more powerful hydrogen peroxide scavenger than the common antioxidant, such as ascorbic acid. In addition, all of these compounds are detected only in AGE, not in raw and other processed garlic preparations. These indicate clearly that not only organosulfur compounds, but also these alkaloids formed during the aging process, may strongly contribute to the antioxidant efficacy of AGE.


   FOOTNOTES
 
1 Published in a supplement to The Journal of Nutrition. Presented at the symposium "Significance of Garlic and Its Constituents in Cancer and Cardiovascular Disease" held April 9–11, 2005 at Georgetown University, Washington, DC. The symposium was sponsored by Strang Cancer Prevention Center, affiliated with Weill Medical College of Cornell University, and Harbor-UCLA Medical Center, and co-sponsored by American Botanical Council, American Institute for Cancer Research, American Society for Nutrition, Life Extension Foundation, General Nutrition Centers, National Nutritional Foods Association, Society of Atherosclerosis Imaging, Susan Samueli Center for Integrative Medicine at the University of California, Irvine. The symposium was supported by Alan James Group, LLC, Agencias Motta, S.A., Antistress AG, Armal, Birger Ledin AB, Ecolandia Internacional, Essential Sterolin Products (PTY) Ltd., Grand Quality LLC, IC Vietnam, Intervec Ltd., Jenn Health, Kernpharm BV, Laboratori Mizar SAS, Magna Trade, Manavita B.V.B.A., MaxiPharm A/S, Nature's Farm, Naturkost S. Rui a.s., Nichea Company Limited, Nutra-Life Health & Fitness Ltd., Oy Valioravinto Ab, Panax, PT. Nutriprima Jayasakti, Purity Life Health Products Limited, Quest Vitamins, Ltd., Sabinco S.A., The AIM Companies, Valosun Ltd., Wakunaga of America Co. Ltd., and Wakunaga Pharmaceutical Co., Ltd. Guest editors for the supplement publication were Richard Rivlin, Matthew Budoff, and Harunobu Amagase. Guest Editor Disclosure: R. Rivlin has been awarded research grants from Wakunaga of America, Ltd. and received an honorarium for serving as co-chair of the conference; M. Budoff has been awarded research grants from Wakunaga of America, Ltd. and received an honorarium for serving as co-chair of the conference; and Harunobu Amagase is employed by Wakunaga of America, Ltd. Back

2 Author Disclosure: No relationships to disclose. Back

4 Abbreviations used: AAPH, 2, 2'-azobis(2-amidinopropane) hydrochloride; ABTS, 2, 2'-azino-di-(3-ethyl-benzthiazoline-6-sulfonic acid); AGE, aged garlic extract; APCI, atmospheric pressure chemical ionization; CID, collision-induced dissociation; LC, liquid chromatography; MeOH, methanol; MTCC, 1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid; MTCdiC, 1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid; SAC, S-allylcysteine; SAMC, S-allylmercaptocysteine; TFA, trifluoroacetic acid; THßC, 1, 2, 3, 4-tetrahydro-ß-carboline derivative; 1a, (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid; 1b, (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-3-carboxylic acid; 2a, (1R, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid; 2b, (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-ß-carboline-1, 3-dicarboxylic acid. Back


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 DISCUSSION
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