LL-C10037α | 93752-54-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: LL-C10037α
• 英文别名: N-[(1S,5S,6S)-5-hydroxy-2-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl]acetamide
• CAS: 93752-54-6
• 化学式: C₈H₉NO₄
• 分子量: 183.164
• InChiKey: ROYHAMHLVIVHPH-APQOSEDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  LL-C10037α 在 sodium acetate 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以50%的产率得到2-acetamidoepoxyquinone
  参考文献：
  名称：

  Structure and absolute stereochemistry of the epoxyquinol LL-C10037.alpha. and related metabolites from Streptomyces LL-C10037

  摘要：

  DOI：

  10.1021/jo00301a039
• 作为产物：
  描述：

  2-acetylamino-1,4-benzoquinone 反应 96.0h， 生成 LL-C10037α
  参考文献：
  名称：

  Biosynthesis of antibiotic LL-C10037.alpha.: the steps beyond 3-hydroxyanthranilic acid

  摘要：

  DOI：

  10.1021/ja00202a039

文献信息

• New Stereoselective Route to the Epoxyquinol Core of Manumycin-Type Natural Products. Synthesis of Enantiopure (+)-Bromoxone, (−)-LL-C10037α, and (+)-KT 8110
  作者：Oliver Block、Georg Klein、Hans-Josef Altenbach、David J. Brauer

  DOI：10.1021/jo991324c

  日期：2000.2.1

  manumycin-type compounds. Starting from p-benzoquinone, optically pure compounds in both forms can be prepared via enzymatic resolution of a derived diacetoxy conduritol. A diepoxy aminoinositol is accessible which can function for formation of enantiopure epoxyquinones and quinols. Examples are given for acylation reactions of this amine with several acyl derivatives. With this approach (-)-LL-C10037alpha and quinones

  描述了一种制备manumycin型化合物的C（7）N核心的实用途径。从对苯醌开始，两种形式的光学纯的化合物都可以通过酶促拆分衍生的二乙酰氧基水合糖醇来制备。可得到二环氧氨基肌醇，其可用于形成对映纯的环氧醌和喹诺酚。给出了该胺与几种酰基衍生物的酰化反应的实例。使用这种方法，可以通过氧化合成具有5R，6S构型的（-）-LL-C10037alpha和醌，例如（+）-KT-8110。另外，描述了到达（+）-溴氧one的短途径。大多数步骤包括简单的环氧化物形成和裂解反应，所有这些都可以以高立体选择性的方式进行。
• Synthesis of (-)-LL-C10037α and Related Manumycin-Type Epoxyquinols
  作者：Peter Wipf、Yuntae Kim、Heike Jahn

  DOI：10.1055/s-1995-4141

  日期：1995.12

  Starting with N-allyloxycarbonyl-protected 2,5-dimethoxyaniline, hypervalent iodine oxidation protocols and selective enone epoxidation provides the Streptomyces metabolite LL-C10037α in nine steps and 7-10% overall yield. In an asymmetric variant of this strategy, (R,R)-pentane-2,4-diol is used as a chiral acetalization agent. The resulting semiquinone spiroacetal, due to an ortho-acylamino substituent that restricts the 1,3-dioxane ring conformation, undergoes face-selective epoxidation and is further functionalized to give (-)-LL-C10037α in 94% ee. These pathways represent the first syntheses of the highly functionalized mC7N core of the manumycins and have been further extended toward the preparation of analogs for SAR studies of this class of antitumor antibiotics. Manumycins inhibit the farnesylation of Ras-protein by PFTase (protein farnesyltransferase).

  以 N-烯丙氧基羰基保护的 2,5-二甲氧基苯胺为起点，通过高价碘氧化规程和选择性烯酮环氧化反应，九步即可得到链霉菌代谢物 LL-C10037δ，总收率为 7-10%。在这一策略的不对称变体中，(R,R)-戊烷-2,4-二醇被用作手性缩醛剂。由于正己胺基取代基限制了 1,3-二恶烷环的构象，由此产生的半醌螺缩醛进行了面选择性环氧化，并进一步官能化，得到了 (-)-LL-C10037 δ，ee 为 94%。这些方法首次合成了马诺霉素的高官能化 mC7N 核心，并进一步扩展到制备类似物，用于该类抗肿瘤抗生素的 SAR 研究。马努霉素能抑制 PFTase（蛋白法尼基转移酶）对 Ras 蛋白的法尼基化。
• Synthesis of the Antitumor Antibiotic LL-C10037.alpha.
  作者：Peter Wipf、Yuntae Kim

  DOI：10.1021/jo00092a004

  日期：1994.7

  (+/-)-LL-C10037 alpha and its C(4)-epimer were prepared in nine steps from 2,5-dimethoxyaniline. The concise synthetic route represents the first synthesis of this highly functionalized antitumor antibiotic and is useful for the preparation of analogs of the putative pharmacophore of the Ras farnesyltransferase inhibitor manumycin.

  (+/-)-LL-C10037 顺式及其 C(4) 异构体，是从 2,5-二甲氧基苯胺开始，经过九步合成得到的。这一简洁的合成路线代表了这一高度官能团化的抗肿瘤抗生素的首次合成，同时对于制备拟药性结构（Ras 法尼基转移酶抑制剂文迪霉素的药效团）的类似物具有实用价值。
• The synthesis of novel analogues of the manumycin family of antibiotics and the antitumour antibiotic LL-C10037α
  作者：Isabelle Kapfer、Norman J. Lewis、Gregor Macdonald、Richard J.K. Taylor

  DOI：10.1016/0040-4039(96)00203-1

  日期：1996.3

  Efficient approaches to the central amino-epoxycyclohexenone core of the manumycin family of antibiotics are described. The use of this methodology to prepare the antitumour antibiotic LL-C10037α and its epimer, both in racemic form, and a number of analogues of manumycin, alisamycin and asukamycin, lacking the C-4 substituent, are then outlined.

  描述了对manumycin家族的中央氨基-环氧-环己烯酮核心的有效方法。然后概述了使用该方法制备外消旋形式的抗肿瘤抗生素LL-C10037α及其差向异构体，以及许多缺少C-4取代基的Manumycin，alisamycin和Asukamycin的类似物的方法。
• PARA-QUINOL DERIVATIVES AND METHODS OF STEREO SELECTIVELY SYNTHESIZING AND USING SAME
  申请人：Plourde Guy L.

  公开号：US20090318548A1

  公开（公告）日：2009-12-24

  This application relates to para-quinol derivatives, such as analogues of manumycins, aranorosins and gymnastatins. This application also relates to methods of synthesizing and using the para-quinol derivatives. In one embodiment of the invention a compound having the chemical structure (I) is provided wherein X 1 and X 2 are carbon atoms either joined by double bond or joined by a single bond and comprising constituents of an epoxide ring or a hydroxyethylene moiety; X 3 and X 4 are carbon atoms either joined by double bond or joined by a single bond and comprising constituents of an epoxide ring; R 1 is selected from the group consisting of branched alkyl chains, unbranched alkyl chains, cycloalkyl groups, aromatic groups, alcohols, ethers, amines, and substituted or unsubstituted ureas, esters, aldehydes and carboxylic acids; and R 2 is selected from the group consisting of H, OH and NHR 3 wherein R 3 is a nitrogen protecting group. In a particular embodiment of the invention R 1 is a polyunsaturated carbon chain as found in biologically active manumycins. The applicant's synthetic method may involve diasteroselective formation of a spirolactone in an oxidative spiroannulation process using tyrosine or a tyrosine derivative having a chiral centre as a starting material.

  本申请涉及对位喹啉衍生物，例如曼纽霉素、阿拉诺罗辛和体操霉素的类似物。本申请还涉及合成和使用对位喹啉衍生物的方法。在发明的一个实施例中，提供了具有化学结构（I）的化合物，其中X1和X2是由双键连接或单键连接的碳原子，并包括环氧环或羟基乙烯基的组分；X3和X4是由双键连接或单键连接的碳原子，并包括环氧环的组分；R1选自支链烷基链，直链烷基链，环烷基团，芳香族团，醇，醚，胺和取代或未取代的脲、酯、醛和羧酸；R2选自H，OH和NHR3，其中R3是氮保护基。在发明的一个特定实施例中，R1是生物活性曼纽霉素中发现的多不饱和碳链。申请人的合成方法可能涉及使用酪氨酸或手性中心的酪氨酸衍生物作为起始材料，在氧化螺环化过程中二面体选择性地形成螺内酯。