(5aS,10bR,11aS)-10b-(1,1-Dimethyl-allyl)-2,3,6,10b,11,11a-hexahydro-5aH-pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-1,4-dione | 191155-40-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (5aS,10bR,11aS)-10b-(1,1-Dimethyl-allyl)-2,3,6,10b,11,11a-hexahydro-5aH-pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-1,4-dione
• 英文别名: (1S,7S,9R)-9-(2-methylbut-3-en-2-yl)-2,5,16-triazatetracyclo[7.7.0.02,7.010,15]hexadeca-10,12,14-triene-3,6-dione
• CAS: 191155-40-5
• 化学式: C₁₈H₂₁N₃O₂
• 分子量: 311.384
• InChiKey: WFKZNFNQEGHGEM-QANKJYHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5aS,10bR,11aS)-10b-(1,1-Dimethyl-allyl)-2,3,6,10b,11,11a-hexahydro-5aH-pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-1,4-dione 在 三丁基膦 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 苯 为溶剂， 生成 8-desmethylardeemin
  参考文献：
  名称：

  Total Synthesis of 5-N-Acetylardeemin and Amauromine:  Practical Routes to Potential MDR Reversal Agents

  摘要：

  The total synthesis of the title compounds has been accomplished. The key step involves the kinetic stereoselective conversion of 19 --> 20. The synthesis of 20 represents for the first time a direct method for constructing exo-pyrroloindoles from protected tryptophans in a highly diastereoselective manner. This step was followed by reverse prenylation (see conversion of 20 --> 27). Using the methodology worked out for the titled compounds, a practical synthesis of several promising MDR reversal agents was possible. Biological data that provided the basis for selection of candidates for advanced study are presented. Preliminary profiling of the zones of the molecules that are responsive to changes while still retaining MDR reversal ability are described. On the basis of these findings, compounds 2, 50, and 51 were selected for more extensive biological follow-up.

  DOI：

  10.1021/ja991558d
• 作为产物：
  描述：

  L-色氨酸甲酯 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 三聚氟氰 、 2,6-二叔丁基吡啶 、 氨 、 四丁基硫酸氢铵 、 4-甲基苯磺酸吡啶 、 碳酸氢钠 、 三氟甲烷磺酸甲酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 (5aS,10bR,11aS)-10b-(1,1-Dimethyl-allyl)-2,3,6,10b,11,11a-hexahydro-5aH-pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-1,4-dione
  参考文献：
  名称：

  Total Synthesis of 5-N-Acetylardeemin and Amauromine:  Practical Routes to Potential MDR Reversal Agents

  摘要：

  The total synthesis of the title compounds has been accomplished. The key step involves the kinetic stereoselective conversion of 19 --> 20. The synthesis of 20 represents for the first time a direct method for constructing exo-pyrroloindoles from protected tryptophans in a highly diastereoselective manner. This step was followed by reverse prenylation (see conversion of 20 --> 27). Using the methodology worked out for the titled compounds, a practical synthesis of several promising MDR reversal agents was possible. Biological data that provided the basis for selection of candidates for advanced study are presented. Preliminary profiling of the zones of the molecules that are responsive to changes while still retaining MDR reversal ability are described. On the basis of these findings, compounds 2, 50, and 51 were selected for more extensive biological follow-up.

  DOI：

  10.1021/ja991558d

文献信息

• Switching a regular tryptophan <i>C4</i>-prenyltransferase to a reverse tryptophan-containing cyclic dipeptide <i>C3</i>-prenyltransferase by sequential site-directed mutagenesis
  作者：Liujuan Zheng、Peter Mai、Aili Fan、Shu-Ming Li

  DOI：10.1039/c8ob01735b

  日期：——

  FgaPT2 from Aspergillus fumigatus catalyzes a regular C4- and its mutant K174A a reverse C3-prenylation of L-tryptophan in the presence of dimethylallyl diphosphate. FgaPT2 also uses tryptophan-containing cyclic dipeptides for C4-prenylation, while FgaPT2_K174A showed almost no activity toward these substrates. In contrast, Arg244 mutants of FgaPT2 accept very well cyclic dipeptides for regular C4-prenylation

  在二磷酸二甲基烯丙酯的存在下，烟曲霉的FgaPT2催化了常规的C4-及其突变体K174A的L-色氨酸的反向C3-异戊二烯化。FgaPT2还使用含色氨酸的环状二肽进行C4-异戊二烯化，而FgaPT2_K174A对这些底物几乎没有活性。相反，FgaPT2的Arg244突变体接受非常好的环状二肽以进行规则的C4-异戊二烯化。在这项研究中，我们证明了FgaPT2_K174F，催化定期C3酪氨酸-prenylation，也可以使用环-大号-Trp-大号-Ala，环-大号-Trp-大号-Trp，环-大号-Trp -甘氨酸，环-大号-Trp-大号-Phe，环-大号-Trp-大号-Pro，和环-大号-Trp-大号-Tyr作为底物，但仅活动少。Lys174和Arg244的组合突变显着提高了对这些环状二肽的接受度。除了cyclo - L -Trp- L-Trp，FgaPT2_K174F_R244X（X = L
• Preparation of pyrrolo[2,3-b]indoles carrying a β-configured reverse C3-dimethylallyl moiety by using a recombinant prenyltransferase CdpC3PT
  作者：Wen-Bing Yin、Xia Yu、Xiu-Lan Xie、Shu-Ming Li

  DOI：10.1039/c000587h

  日期：——

  Six β-configured reversely C3-prenylated pyrrolo[2,3-b]indoles were successfully prepared by using a recombinant prenyltransferase from Neosartorya fischeri. For this purpose, the putative prenyltransferase gene NFIA_074280 (termed herewith cdpC3PT) was cloned into pQE60 and overexpressed in Escherichia coli. The overproduced His6-CdpC3PT was purified to near homogeneity and incubated with five cyclic tryptophan-containing dipeptides in the presence of dimethylallyl diphosphate (DMAPP). All of the substrates were accepted by CdpC3PT and converted to reversely C3-prenylated pyrrolo[2,3-b]indoles. Using cyclo-L-Trp-L-Trp as substrate, both mono- and diprenylated derivatives were obtained. The structures of the enzymatic products were confirmed by HR-ESI-MS, 1H- and 13C-NMR analyses as well as by long-range 1H-13C connectivities in heteronuclear multiple-bond correlation (HMBC) spectra after preparative isolation. 1H-1H spatial correlations in nuclear overhauser effect spectroscopy (NOESY) were used for determination of absolute configuration. The KM values were determined at about 1.5 mM for DMAPP and in the range from 0.22 to 5.5 mM for cyclic dipeptides. The turnover number kcat were found in the range of 0.023 to 0.098 s−1 and specificity constants kcat/KM from 14.2 to 122.7 M−1 s−1. In contrast to the products of AnaPT bearing α-configured C3-dimethylallyl residues, the C3-prenyl moieties in the products of CdpC3PT have a β-configuration. Discovery and characterisation of CdpC3PT expand the usage of the chemoenzymatic approach for stereospecific synthesis of C3-prenylated derivatives.

  使用来自 Neosartorya fischeri 的重组异戊二烯转移酶成功制备了六种 β 配置的反向 C3 异戊二烯化吡咯并 [2,3-b] 吲哚。为此目的，将推定的异戊烯基转移酶基因NFIA_074280（本文称为cdpC3PT）克隆到pQE60中并在大肠杆菌中过表达。将过量产生的 His6-CdpC3PT 纯化至接近均质，并在二甲基烯丙基二磷酸 (DMAPP) 存在下与五种含环状色氨酸的二肽一起孵育。所有底物均被 CdpC3PT 接受并转化为反向 C3-异戊二烯化吡咯并[2,3-b]吲哚。以环-L-色氨酸-L-色氨酸为底物，得到单烯化和二烯化衍生物。酶产物的结构通过 HR-ESI-MS、1H 和 13C-NMR 分析以及制备分离后异核多重键关联 (HMBC) 光谱中的长程 1H-13C 连接性得到证实。核欧沃豪瑟效应光谱 (NOESY) 中的 1H-1H 空间相关性用于确定绝对构型。 DMAPP 的 KM 值测定为约 1.5 mM，环状二肽的 KM 值范围为 0.22 至 5.5 mM。周转数 kcat 的范围为 0.023 至 0.098 s±1，特异性常数 kcat/KM 的范围为 14.2 至 122.7 M±1 s±1。与带有α-配置的C3-二甲基烯丙基残基的AnaPT 产物相比，CdpC3PT 产物中的C3-异戊二烯基部分具有β-配置。 CdpC3PT 的发现和表征扩展了化学酶方法在 C3-异戊二烯化衍生物立体定向合成中的用途。
• ANALOGUES OF N-ACETYLARDEEMIN, METHOD OF PREPARATION AND USES THEREOF
  申请人：The Trustees of Columbia University in the City of New York

  公开号：EP0815111B1

  公开（公告）日：2007-10-10
• Total Synthesis of 5-<i>N</i>-Acetylardeemin and Amauromine:  Practical Routes to Potential MDR Reversal Agents
  作者：Kristopher M. Depew、Stephen P. Marsden、Danuta Zatorska、Andrzej Zatorski、William G. Bornmann、Samuel J. Danishefsky

  DOI：10.1021/ja991558d

  日期：1999.12.1

  The total synthesis of the title compounds has been accomplished. The key step involves the kinetic stereoselective conversion of 19 --> 20. The synthesis of 20 represents for the first time a direct method for constructing exo-pyrroloindoles from protected tryptophans in a highly diastereoselective manner. This step was followed by reverse prenylation (see conversion of 20 --> 27). Using the methodology worked out for the titled compounds, a practical synthesis of several promising MDR reversal agents was possible. Biological data that provided the basis for selection of candidates for advanced study are presented. Preliminary profiling of the zones of the molecules that are responsive to changes while still retaining MDR reversal ability are described. On the basis of these findings, compounds 2, 50, and 51 were selected for more extensive biological follow-up.