Simone Manetto, Diego Caprioglio, Gianpaolo Grassi, Bruno Botta, Francesco Gasparrini, Giulia Mazzoccanti* and Giovanni Appendino*,
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To rationalize these puzzling observations, the kinetics of thermal (100 °C) racemization of enantiopure cannabichromene (<b>1a</b>) was evaluated by enantioselective ultrahigh performance liquid chromatography in solvents (decalin and isopropyl alcohol, neat and acidified with TFA) and surfaces (native and silanized borosilicate glass) of complementary polarity. Optical stability was more than halved in isopropanol compared to decalin (<i>t</i><sub>1/2</sub> 50 h vs 135 h), but acidification had no effect on racemization. However, contact with a solid surface dramatically accelerated the process, with a <i>t</i><sub>1/2</sub> of only 6 h on both glass surfaces. The overall extent of racemization of enantiopure CBC (<b>1a</b>) was compared under conditions commonly used for decarboxylation (heating at 130 °C) between a decalin solution and a thin film on three different surfaces (native and silanized borosilicate glass and powdered blank cannabis biomass). In line with the kinetic data, a significant erosion of enantiopurity was observed on all solid surfaces compared to the solution. These observations suggest that discrepancies in the reported enantiomeric purity of natural CBC could be not only of biogenetic derivation but also be associated with the decarboxylation protocol of cannabichromenic acid (<b>1b</b>). These findings, while relevant for the exploitation of the bioactivity of natural CBC for human health, should also prompt the adoption of a standardized decarboxylation protocol for the studies on the configurational status of CBC (<b>1a</b>) in cannabis and, in general, of cannabinochromanoids in nature.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"87 12","pages":"2724–2729 2724–2729"},"PeriodicalIF":3.6000,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cannabichromene (CBC) Shows Matrix-Dependent Thermal Configurational Stability\",\"authors\":\"Simone Manetto, Diego Caprioglio, Gianpaolo Grassi, Bruno Botta, Francesco Gasparrini, Giulia Mazzoccanti* and Giovanni Appendino*, \",\"doi\":\"10.1021/acs.jnatprod.4c0086110.1021/acs.jnatprod.4c00861\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The optical purity of cannabichromene (CBC, <b>1a</b>) is affected by the matrix in which it is generated by thermolysis from its native carboxylated form (cannabichromenic acid, CBCA, <b>1b</b>). Thus, thermolysis at 130 °C <i>in planta</i> caused a marked decrease of the enantiomeric excess (ee), while, under the same conditions, only a modest decrease of optical purity was observed when thermolysis was carried out <i>in extracto</i>. To rationalize these puzzling observations, the kinetics of thermal (100 °C) racemization of enantiopure cannabichromene (<b>1a</b>) was evaluated by enantioselective ultrahigh performance liquid chromatography in solvents (decalin and isopropyl alcohol, neat and acidified with TFA) and surfaces (native and silanized borosilicate glass) of complementary polarity. Optical stability was more than halved in isopropanol compared to decalin (<i>t</i><sub>1/2</sub> 50 h vs 135 h), but acidification had no effect on racemization. However, contact with a solid surface dramatically accelerated the process, with a <i>t</i><sub>1/2</sub> of only 6 h on both glass surfaces. 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引用次数: 0
摘要
大麻红素(CBC, 1a)的光学纯度受其天然羧化形式(大麻红素酸,CBCA, 1b)通过热裂解产生的基质的影响。因此,植物在130°C下的热裂解导致了对映体过量(ee)的显著降低,而在相同条件下,在萃取物中进行热裂解时,只观察到光学纯度的适度降低。为了使这些令人困惑的观察结果合理化,采用对映选择性超高效液相色谱法,在互补极性的溶剂(十氢化萘和异丙醇,纯的和用TFA酸化的)和表面(天然的和硅化的硼硅酸盐玻璃)中,评估了对映纯大麻二色胺(1a)的热(100°C)消旋动力学。与十氢化萘相比,异丙醇的光学稳定性降低了一半以上(1/2 50 h vs 135 h),但酸化对外消旋作用没有影响。然而,与固体表面的接触大大加速了这一过程,两个玻璃表面的t1/2仅为6小时。在通常用于脱羧的条件下(130°C加热),比较了十氢化萘溶液和薄膜在三种不同表面(天然和硅化硼硅酸盐玻璃和粉末空白大麻生物质)上的外消旋化的总体程度。与动力学数据一致,与溶液相比,在所有固体表面上观察到明显的对映不纯性侵蚀。这些观察结果表明,报道的天然CBC对映体纯度的差异可能不仅是生物遗传衍生的,而且与大麻红素酸的脱羧方案有关(1b)。这些发现虽然与开发天然CBC对人类健康的生物活性有关,但也应促使采用标准化脱羧协议,以研究大麻中CBC (1a)的构型状态,以及一般情况下研究自然界中的大麻素类黄酮。
The optical purity of cannabichromene (CBC, 1a) is affected by the matrix in which it is generated by thermolysis from its native carboxylated form (cannabichromenic acid, CBCA, 1b). Thus, thermolysis at 130 °C in planta caused a marked decrease of the enantiomeric excess (ee), while, under the same conditions, only a modest decrease of optical purity was observed when thermolysis was carried out in extracto. To rationalize these puzzling observations, the kinetics of thermal (100 °C) racemization of enantiopure cannabichromene (1a) was evaluated by enantioselective ultrahigh performance liquid chromatography in solvents (decalin and isopropyl alcohol, neat and acidified with TFA) and surfaces (native and silanized borosilicate glass) of complementary polarity. Optical stability was more than halved in isopropanol compared to decalin (t1/2 50 h vs 135 h), but acidification had no effect on racemization. However, contact with a solid surface dramatically accelerated the process, with a t1/2 of only 6 h on both glass surfaces. The overall extent of racemization of enantiopure CBC (1a) was compared under conditions commonly used for decarboxylation (heating at 130 °C) between a decalin solution and a thin film on three different surfaces (native and silanized borosilicate glass and powdered blank cannabis biomass). In line with the kinetic data, a significant erosion of enantiopurity was observed on all solid surfaces compared to the solution. These observations suggest that discrepancies in the reported enantiomeric purity of natural CBC could be not only of biogenetic derivation but also be associated with the decarboxylation protocol of cannabichromenic acid (1b). These findings, while relevant for the exploitation of the bioactivity of natural CBC for human health, should also prompt the adoption of a standardized decarboxylation protocol for the studies on the configurational status of CBC (1a) in cannabis and, in general, of cannabinochromanoids in nature.
期刊介绍:
The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
When new compounds are reported, manuscripts describing their biological activity are much preferred.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.