stevioside

• 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
• 英文名称: stevioside
• 英文别名: SureCN33428；[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (1R,5R,9S,13S)-13-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-5,9-dimethyl-14-methylidenetetracyclo[11.2.1.01,10.04,9]hexadecane-5-carboxylate
• 化学式: C₃₈H₆₀O₁₈
• 分子量: 804.884
• InChiKey: UEDUENGHJMELGK-CFOPWMEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  56
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  295
• 氢给体数：
  11
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  stevioside 在 盐酸 作用下， 以 水 为溶剂， 以59%的产率得到α-槐糖 单水合物
  参考文献：
  名称：

  Sweet and bitter principles of the Chinese plant drug, Bai-Yun-Shen: Revision of the assignment of the source plant and isolation of two new diterpene glycosides.

  摘要：

  将中国植物药 "白云参 "的来源植物定为唇形科植物丹参（Salvia digitaloides DIELS），并修正为同科植物白云参（Phlomis betonicoides DIELS）。从该植物的根中分离出了一种名为 phlomisoside-I (5) 的甜苷和一种名为 phlomisoside-II (6) 的苦苷。经证实，这两种化合物的苷元都是白云醇（7，呋喃-唇丹型二萜），即白云苷（1）的苷元。5 和 6 的结构已被阐明，分别为 3-O-α-rhamnopyranosyl-(1→2)-β-glucopyranoside 和 7 的 3-O-sophoroside 。

  DOI：

  10.1248/cpb.33.4275
• 作为产物：
  描述：

  13-O-β-sophorosyl-steviol 、 2,3,4,6-四乙酰氧基-alpha-D-吡喃葡萄糖溴化物 在 吡啶 、 甲醇 、 cyclodextrin glucanotransferase 、 乙酸酐 、 γ-环糊精 、 barium(II) oxide 、 starch 作用下， 生成 stevioside 、 13-O-[β-maltosyl(1->2)-β-D-glucosyl]-19-O-β-D-glucosyl-steviol 、 13-O-[β-maltotriosyl(1->2)-β-D-glucosyl]-19-O-β-D-glucosyl-steviol 、 4''-O-α-maltotriosyl-stevioside
  参考文献：
  名称：

  Solubilization of Steviolbioside and Steviolmonoside with .GAMMA.-Cyclodextrin and Its Application to Selective Syntheses of Better Sweet Glycosides from Stevioside and Rubusoside.

  摘要：

  1、甜菊糖苷（S）和红没药苷（RU）的 13-O-糖基的 4-α-葡萄糖基化可显著增加甜度。对 S 和 RU 的 19-COO-β-葡萄糖基连接进行皂化，分别得到甜菊糖甙（SB）（=13-O-β-槐糖基-烷二醇）和甜菊糖单苷（SM）（=13-O-β-葡萄糖基-烷二醇），这两种物质在醋酸盐缓冲液中的溶解度都很低。研究发现，γ-环糊精（γ-CD）存在时，SM 和 SB 在缓冲溶液中的溶解度显著增加。借助 γ-CD 将 SB 溶解在缓冲溶液中，然后使用环糊精葡聚糖转移酶-淀粉系统对溶液进行 1，4-α-反式葡萄糖基化，得到在 13-O-糖基分子处被葡萄糖基化的产物混合物。这种混合物被乙酰化，乙酸酯经过 19-COOH 的化学β-葡萄糖基化，然后脱乙酰化，得到甜度优于 S 的化合物。

  DOI：

  10.1248/cpb.39.3172

文献信息

• [EN] INHIBITORS OF ANTIBIOTIC RESISTANCE MEDIATED BY ARN T<br/>[FR] INHIBITEURS DE RÉSISTANCE AUX ANTIBIOTIQUES MÉDIÉE PAR L'ARN T
  申请人：UNIV DEGLI STUDI ROMA LA SAPIENZA

  公开号：WO2021014422A1

  公开（公告）日：2021-01-28

  The present invention relates to diterpene compounds of general formula (I) capable of contrasting the antibiotic-resistance mediated by the ArnT enzyme, to their use as a medicament, in particular for use as an adjuvant of an antibiotic therapy in the treatment of antibiotic-resistant bacterial infections. The invention relates also to associations of one or more of the compounds of formula (I) with at least another active ingredient, in particular an antibacterial agent and/or an antibiotic, and compositions comprising one or more compounds of formula (I) or the association according to the present invention and at least one pharmaceutically acceptable excipient and/or carrier as well as to products, in particular medical devices, comprising at least a compound, an association or a composition according to the present invention. Moreover, the invention relates to the use of compounds of formula (I) to sensitize a bacterium to an antibacterial agent or an antibiotic, for example, colistin (polymyxin E) or polymyxin B and to an in vivo or in vitro method for sensitizing a bacterium to an antibacterial agent or an antibiotic comprising the exposure of said bacterium to one or more compounds of formula (I) together with colistin.

  本发明涉及通式（I）的二萜化合物，其能够对抗由ArnT酶介导的抗生素耐药性，以及它们作为药物的用途，特别是作为抗生素治疗中的辅助剂，用于治疗抗生素耐药性细菌感染。本发明还涉及将通式（I）的一个或多个化合物与至少另一种活性成分，特别是抗菌剂和/或抗生素，结合在一起的组合物，以及包含一个或多个通式（I）化合物或根据本发明的组合物和至少一种药用可接受的载体和/或载体的组合物，以及包含至少一种化合物、组合物或组合物的产品，特别是医疗器械。此外，本发明涉及使用通式（I）的化合物使细菌对抗菌剂或抗生素敏感化的用途，例如，科利斯汀（多粘菌素E）或多粘菌素B，以及一种体内或体外的方法，用于使细菌对抗菌剂或抗生素敏感化，包括将该细菌暴露于与科利斯汀一起使用的一个或多个通式（I）化合物。
• Tanaka, Takashi; Kohda, Hiroshi; Tanaka, Osamu, Agricultural and Biological Chemistry, <hi>1981</hi>, vol. 45, # 9, p. 2165 - 2166
  作者：Tanaka, Takashi、Kohda, Hiroshi、Tanaka, Osamu、Chen, Feng-Huai、Chou, Wen-Hwa、Leu, Jian-Liang

  DOI：——

  日期：——
• Sweet and bitter principles of the Chinese plant drug, Bai-Yun-Shen: Revision of the assignment of the source plant and isolation of two new diterpene glycosides.
  作者：TAKASHI TANAKA、OSAMU TANAKA、ZHONGWEN LIN、JUN ZHOU

  DOI：10.1248/cpb.33.4275

  日期：——

  The assignment of the source plant of the Chinese plant drug "Bai-Yun-Shen" as Salvia digitaloides DIELS (Labiatae), was revised to Phlomis betonicoides DIELS of the same family. From roots of this plant, a sweet glycoside named phlomisoside-I (5) and a bitter glycoside named phlomisoside-II (6) were isolated. The aglycone of both compounds was proved to be baiyunol (7, furano-labdane-type diterpene), the aglycone of baiyunoside (1), which has already been isolated as the sweet principle from this plant drug. The structures of 5 and 6 were elucidated as the 3-O-α-rhamnopyranosyl-(1→2)-β-glucopyranoside and the 3-O-sophoroside of 7, respectively.

  将中国植物药 "白云参 "的来源植物定为唇形科植物丹参（Salvia digitaloides DIELS），并修正为同科植物白云参（Phlomis betonicoides DIELS）。从该植物的根中分离出了一种名为 phlomisoside-I (5) 的甜苷和一种名为 phlomisoside-II (6) 的苦苷。经证实，这两种化合物的苷元都是白云醇（7，呋喃-唇丹型二萜），即白云苷（1）的苷元。5 和 6 的结构已被阐明，分别为 3-O-α-rhamnopyranosyl-(1→2)-β-glucopyranoside 和 7 的 3-O-sophoroside 。
• Solubilization of Steviolbioside and Steviolmonoside with .GAMMA.-Cyclodextrin and Its Application to Selective Syntheses of Better Sweet Glycosides from Stevioside and Rubusoside.
  作者：Kazuhiro OHTANI、Yoko AIKAWA、Yoshiko FUJISAWA、Ryoji KASAI、Osamu TANAKA、Kazuo YAMASAKI

  DOI：10.1248/cpb.39.3172

  日期：——

  1, 4-α-Glucosylation at the 13-O-glycosyl moiety of stevioside (S) and rubusoside (RU) results in a significant increase of sweetness. Saponification of the 19-COO-β-glucosyl linkage of S and RU yielded steviolbioside (SB) (=13-O-β-sophorosyl-steviol) and steviolmonoside (SM) (=13-O-β-glucosyl-steviol), respectively, both of which are poorly soluble in an acetate buffer. It was found that the solubilities of SM and SB in the buffer solution were remarkably increased in the presence of γ-cyclodextrin (γ-CD). SB was solubilized in the buffer solution with the aid of γ-CD, and the solution was subjected to 1, 4-α-transglucosylation by using a cyclodextrin glucanotransferase-starch system to give a mixture of products which were glucosylated at the 13-O-glycosyl moiety. This mixture was acetylated, and the acetate was subjected to chemical β-glucosylation of 19-COOH followed by deacetylation to afford compounds which have superior sweetness to S. In the same way, derivatives with superior sweetness were selectively prepared from RU through SM.

  1、甜菊糖苷（S）和红没药苷（RU）的 13-O-糖基的 4-α-葡萄糖基化可显著增加甜度。对 S 和 RU 的 19-COO-β-葡萄糖基连接进行皂化，分别得到甜菊糖甙（SB）（=13-O-β-槐糖基-烷二醇）和甜菊糖单苷（SM）（=13-O-β-葡萄糖基-烷二醇），这两种物质在醋酸盐缓冲液中的溶解度都很低。研究发现，γ-环糊精（γ-CD）存在时，SM 和 SB 在缓冲溶液中的溶解度显著增加。借助 γ-CD 将 SB 溶解在缓冲溶液中，然后使用环糊精葡聚糖转移酶-淀粉系统对溶液进行 1，4-α-反式葡萄糖基化，得到在 13-O-糖基分子处被葡萄糖基化的产物混合物。这种混合物被乙酰化，乙酸酯经过 19-COOH 的化学β-葡萄糖基化，然后脱乙酰化，得到甜度优于 S 的化合物。