人参皂苷F1 | 53963-43-2

• 物质功能分类: 生物化工 - 提取物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 人参皂苷F1
• 中文别名: 人参皂苷-F1；人参皂苷 F1
• 英文名称: ginsenoside F1
• 英文别名: 3β,6α,12β,20S-tetrahydroxydammar-24-ene 20-O-β-D-glucopyranoside；20-O-β-D-glucopyranosyl-20(S)-protopanaxatriol；Ginsenoside F₁；ginsenoside-F₁；ginsenoside-F(1)；ginsennoside F1；(2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[(2S)-6-methyl-2-[(3S,5R,6S,8R,9R,10R,12R,13R,14R,17S)-3,6,12-trihydroxy-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]hept-5-en-2-yl]oxyoxane-3,4,5-triol
• CAS: 53963-43-2
• 化学式: C₃₆H₆₂O₉
• 分子量: 638.883
• InChiKey: XNGXWSFSJIQMNC-FIYORUNESA-N

物化性质

• 熔点：
  >165°C (dec.)
• 沸点：
  751.7±60.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  45
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  160
• 氢给体数：
  7
• 氢受体数：
  9

安全信息

• WGK Germany：
  3

制备方法与用途

生物活性 Ginsenoside F1 是人参的一种药物成分，已知具有抗衰老、抗氧化和抗癌作用，并能保护角质形成细胞。它对 CYP3A4 的抑制作用表现为竞争性，Ki值为67.8 ± 16.2 μM；而对 CYP2D6 的抑制作用较弱。

靶点

Target	Value
CYP3A4 (Cell-free assay)	67.8 μM(Ki)

体外研究 Ginsenoside F1 已显示出抗癌、抗衰老和抗氧化作用，并能竞争性地抑制 CYP3A4 活性，对 CYP2D6 的抑制作用较弱。在 MTT 实验中，最高浓度（200 μM）的 ginsenoside F1 使细胞存活率达到了68%。

体内研究 使用 ApoE-/- 小鼠进行实验，这些小鼠被喂食高脂饮食并口服给予 Ginsenoside F1 （50 mg/kg/day），持续8周。与模型组相比，接受 Ginsenoside F1 治疗的小鼠显著减少了病变面积。

化学性质 Ginsenoside F1 是一种白色结晶粉末，可溶于甲醇、乙醇和 DMSO 等有机溶剂，来源于人参根茎及绞股蓝。

用途 用于含量测定/鉴定/药理实验等。
药理作用：提高人体力和智力的活动能力，增强机体对有害刺激的非特异性抵抗力。

人参皂苷 F1 是人参皂苷 Rg1 的代谢产物，具有抗氧化、抗衰老活性，并对皮肤有美白效果。

反应信息

• 作为反应物：
  描述：

  尿苷(5')二氢二磷酰(1)-alpha-D-葡萄糖 、 人参皂苷F1 在 β-(1,4)-galactosyltransferase 、 epimerase 、 alkaline phosphatase 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 72.0h， 以51%的产率得到20-O-lactosylprotopanaxatriol
  参考文献：
  名称：

  Regioselective Enzymatic Glycosylation of Natural Polyhydroxylated Compounds:  Galactosylation and Glucosylation of Protopanaxatriol Ginsenosides¹

  摘要：

  Ginsenoside Rg(1) (1), the most representative Ginsenoside from Panax Ginseng C. A. Meyer belonging to the protopanaxatriol family, has been galactosylated by action of the beta-(1,4)-galactosyltransferase (GalT) from bovine colostrum, using UDP-galactose as an activated sugar donor. The enzyme showed the well-known specificity for the formation of a beta -linkage with the C-4 OH of the glucose acceptor, but it was not able to discriminate between the two glucose moieties of 1, giving a mixture of mono-and digalactosylated derivatives. Other natural Rg(1)-analogues such as F1, Rh-1, Re, as well as the synthetic derivative 6'-O-acetyl-Rg(1) have been also galactosylated, giving monolactosyl derivatives. GalT was also able to accept UDP-glucose as an activated sugar donor, giving rise to cellobiosyl derivatives of Rg(1).

  DOI：

  10.1021/jo001424e
• 作为产物：
  描述：

  人参皂甙RE 在 Penicillium decumbens naringinase 、 Penicillium sp. hesperidinase 作用下， 生成 人参皂苷F1
  参考文献：
  名称：

  从原托那沙三醇型人参皂苷混合物中酶法制备人参皂苷Rg2，Rh1和F1。

  摘要：

  在研究各种糖苷水解酶水解前托沙三醇型皂苷混合物的过程中，发现米曲霉的粗β-半乳糖苷酶和青霉的粗乳糖酶以高收率形成了两种次要皂苷，人参皂苷Rg 2和Rh 1。分别。此外，从枯草青霉中提取的柚皮苷酶的粗制制剂容易水解原托那沙三醇型皂苷混合物，得到肠细菌代谢产物人参皂甙F 1为主要产物。来自青霉菌属的橙皮苷酶的粗制品。将人参皂苷Re选择性水解为人参皂苷Rg1。这是关于酶法制备次要皂苷，人参皂苷Rg 2和Rh 1以及肠道细菌代谢产物人参皂苷F 1的首次报道。

  DOI：

  10.1055/s-2003-38476

文献信息

• Synthesis of 20S-Protopanaxatriol β-D-Glucopyranosides
  作者：L. N. Atopkina、V. A. Denisenko

  DOI：10.1007/s10600-019-02618-6

  日期：2019.1

  Condensation of 20S-protopanaxatriol (3β,6α,12β,20S-tetrahydroxydammar-24-ene) (1) with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (2) in the presence of Ag2O in CH2Cl2 gave a mixture of acetylated 3-, 12-, 20-, 3,12-di-, and 3,20-di-O-β-D-glucopyranosides 3–7 that was dominated by 3-O-β-Dglucopyranoside tetraacetate 3 (47%). Subsequent deacetylation by sodium methoxide produced free β-D-glucopyranosides 8–12, three of which were identical to chikusetsusaponin-L10, ginsenoside-F1, and ginsenoside-Ia, which were isolated earlier from leaves of Panax japonicus and P. ginseng. 3-Mono- and 3,12-di-O-β-D-glucopyranosides 8 and 11 were prepared for the first time.

  在 Ag2O 存在下，20S-原人参三醇（3β,6α,12β,20S-四羟基达玛-24-烯）（1）与 2,3,4,6-四-O-乙酰基-α-D-吡喃葡萄糖溴化物（2）在 CH2Cl2 中缩合，得到乙酰化的 3-、12-、20-、3,12-二和 3,20- 二-O-β-D-吡喃葡萄糖苷 3-7 的混合物、12-、20-、3,12-二和 3,20- 二-O-β-D-吡喃葡萄糖苷 3-7 的混合物，其中以 3-O-β-D 吡喃葡萄糖苷四乙酸酯 3（47%）为主。随后用甲醇钠进行脱乙酰化，产生了游离β-D-吡喃葡萄糖苷 8-12，其中三个与早先从日本三七和人参叶中分离出的千层塔皂甙-L10、人参皂甙-F1 和人参皂甙-Ia 相同。首次制备了 3-甲基和 3,12- 二-O-β-D-吡喃葡萄糖苷 8 和 11。
• Regioselective Enzyme-Mediated Acylation of Polyhydroxy Natural Compounds. A Remarkable, Highly Efficient Preparation of 6'-Acetyl and 6'-O-Carboxyacetyl Ginsenoside Rg1
  作者：Bruno Danieli、Monica Luisetti、Sergio Riva、Anna Bertinotti、Enzio Ragg、Leonardo Scaglioni、Ezio Bombardelli

  DOI：10.1021/jo00117a012

  日期：1995.6

  Lipase B from Candida antarctica has been shown to be an efficient catalyst for the regioselective acylation of the dammarane type glucoside ginsenoside Rg(1) (1) on reaction with vinyl acetate in t-AmOH, affording the corresponding 6'-O-acetyl derivative 1b in high yield. The structure of 1b was determined through a careful inspection of its H-1 NMR at 600 MHz, which allowed for the complete assignment of the signals of the sugar's protons. The introduction of a carboxyacetyl residue was then investigated using different protocols. The best results were obtained with a two-step sequence involving the preliminary enzymatic acylation of 1 with bis(2,2,2-trichloroethyl) malonate to give the mixed malonyl derivative 1f, followed by selective chemical hydrolysis with Zn/AcOH to the 6'-O-carboxyacetyl ginsenoside Rg(1) (1e).
• Characterization of Metabolism and <i>in Vitro</i> Permeability Study of Notoginsenoside R1 from Radix Notoginseng
  作者：Jian-Qing Ruan、Weng-Im Leong、Ru Yan、Yi-Tao Wang

  DOI：10.1021/jf1005885

  日期：2010.5.12

  As a main and characteristic constituent in Radix notoginseng, the fate of notoginsenoside R1 (NGR1) in human is largely unknown. The present study investigated, for the first time, NGR1 metabolism by human intestinal bacteria and liver subcellular fractions, and permeability properties of NGR1 and resultant metabolites on a Caco-2 model. Samples were qualitatively analyzed using HPLC-MS/MS and quantitatively determined using HPLC-UV. When incubated with pooled human intestinal bacteria anaerobically, NGR1 showed biphasic elimination: an insignificant decrease in the first 8 h followed by a rapid elimination during 8-48 h. Four metabolites, three unambiguously identified as ginsenosides Rg1, F1 and 20(S)-protopanaxatriol formed via stepwise deglycosylation. and one tentatively assigned as a dehydrogenated protopanaxatriol with transformation occurring at the tetracyclic triterpenoid skeleton, were produced sequentially. Rg1 and F1 were formed transiently at low apparent velocities, while 20(S)-protopanaxatriol was the major metabolite with a formation rate close to the rate of NGR1 elimination and a low elimination rate. NGR1 remained intact in human liver S9 or microsomes over 1 h. Transport study of NGR1 and its metabolites revealed an ascending permeability order with stepwise deglycosylation. Taken together, the results revealed a determinant role of intestinal bacteria in the overall disposition and potential bioactivity of NGR1 in human.
• A Novel Ginsenosidase from an Aspergillus Strain Hydrolyzing 6-O-Multi-Glycosides of Protopanaxatriol-Type Ginsenosides, Named Ginsenosidase Type IV
  作者：Dong-Ming Wang

  DOI：10.4014/jmb.1101.01044

  日期：2011.10.28

  Herein, a novel ginsenosidase, named ginsenosidase type IV, hydrolyzing 6-O-multi-glycosides of protopanaxatriol-type ginsenosides (PPT), such as Re, R1, Rf, and Rg2, was isolated from the Aspergillus sp. 39g strain, purified, and characterized. Ginsenosidase type IV was able to hydrolyze the 6-O-alpha-L-(1 -> 2)-rhamnoside of Re and the 6-O-beta-D-(1 -> 2)-xyloside of R1 into ginsenoside Rg1. Subsequently, it could hydrolyze the 6-O-beta-D-glucoside of Rg1 into F1. Similarly, it was able to hydrolyze the 6-O-alpha-L-(1 -> 2)-rhamnoside of Rg2 and the 6-O-beta-D-(1 -> 2)-glucoside of Rf into Rh1, and then further hydrolyze Rh1 into its aglycone. However, ginsenosidase type IV could not hydrolyze the 3-O- or 20-O-glycosides of protopanaxadiol-type ginsenosides (PPD), such as Rb1, Rb2, Rb3, Rc, and Rd. These exhibited properties are significantly different from those of glycosidases described in Enzyme Nomenclature by the NC-IUBMB. The optimal temperature and pH for ginsenosidase type IV were 40 degrees C and 6.0, respectively. The activity of ginsenosidase type IV was slightly improved by the Mg2+ ion, and inhibited by Cu2+ and Fe2+ ions. The molecular mass of the enzyme, based on SDS-PAGE, was noted as being approximately 56 kDa.
• Characterization of Panax ginseng UDP-Glycosyltransferases Catalyzing Protopanaxatriol and Biosyntheses of Bioactive Ginsenosides F1 and Rh1 in Metabolically Engineered Yeasts
  作者：Wei Wei、Pingping Wang、Yongjun Wei、Qunfang Liu、Chengshuai Yang、Guoping Zhao、Jianmin Yue、Xing Yan、Zhihua Zhou

  DOI：10.1016/j.molp.2015.05.010

  日期：2015.9

  Ginsenosides, the main pharmacologically active natural compounds in ginseng (Panax ginseng), are mostly the glycosylated products of protopanaxadiol (PPD) and protopanaxatriol (PPT). No uridine diphosphate glycosyltransferase (UGT), which catalyzes PPT to produce PPT-type ginsenosides, has yet been reported. Here, we show that UGTPg1, which has been demonstrated to regio-specifically glycosylate the C20-OH of PPD, also specifically glycosylates the C20-OH of PPT to produce bioactive ginsenoside F1. We report the characterization of four novel UGT genes isolated from P. ginseng, sharing high deduced amino acid identity (>84%) with UGTPg1. We demonstrate that UGTPg100 specifically glycosylates the C6-OH of PPT to produce bioactive ginsenoside Rh1, and UGTPg101 catalyzes PPT to produce F1, followed by the generation of ginsenoside Rg1 from F1. However, UGTPg102 and UGTPg103 were found to have no detectable activity on PPT. Through structural modeling and site-directed mutagenesis, we identified several key amino acids of these UGTs that may play important roles in determining their activities and substrate regio-specificities. Moreover, we constructed yeast recombinants to biosynthesize F1 and Rh1 by introducing the genetically engineered PPT-producing pathway and UGTPg1 or UGTPg100. Our study reveals the possible biosynthetic pathways of PPT-type ginsenosides in Panax plants, and provides a sound manufacturing approach for bioactive PPT-type ginsenosides in yeast via synthetic biology strategies.