(+)-nodulisporic acid A | 163120-03-4

• 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: (+)-nodulisporic acid A
• 英文别名: nodulisporic acid A；nodulisporic acid；(2E,4E)-5-[(3S,4S,7S,8S,9R,12S,23R,24S,28S)-7,24-dihydroxy-3,4,8,20,20,22,22-heptamethyl-27-oxo-28-prop-1-en-2-yl-21-oxa-1-azaoctacyclo[13.13.1.02,14.03,12.04,9.017,25.018,23.026,29]nonacosa-2(14),15,17(25),18,26(29)-pentaen-8-yl]-2-methylpenta-2,4-dienoic acid
• CAS: 163120-03-4
• 化学式: C₄₃H₅₃NO₆
• 分子量: 679.897
• InChiKey: UNCVXXVJJXJZII-QLETUHIQSA-N

物化性质

• 熔点：
  250-255°
• 比旋光度：
  D22 +13° (c = 0.4 in CHCl3)
• 沸点：
  832.1±65.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  50
• 可旋转键数：
  4
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+)-nodulisporic acid A 生成
  参考文献：
  名称：

  Nodulisporic acid side-Chain modifications: access to the 2″, 3″, 4″, and 6″ registers

  摘要：

  Efficient routes to access the 2", 3", 4", and 6" registers of the nodulisporic acid (NsA) side chain are disclosed. A mild one-carbon, Ph2C=NCH(2)Cequivalent toN mediated homologation of NsA's 3"-aldehyde permitted access to the 4"-register. Curtius reaction of NsA's 3"-acid yielded the corresponding 2"-aldehyde 4 from which the unnatural Delta(2" 3")-olefin isomer 2b was obtained. In addition, Arndt-Eistert reactions of the parent NsA permitted a one-carbon homologation to the 6" register. These efforts identified new analogues with significant flea activity and illustrated the biological significance of unsaturation at the 1",2" register. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00826-0

文献信息

• Synthesis of Side Chain Truncated 3‘ ‘-Aldehyde, 3‘ ‘-Carboxylic Acid, and 1‘ ‘-Aldehyde from Nodulisporic Acid A
  作者：Prasun K. Chakravarty、Sriram Tyagarajan、Thomas L. Shih、Steve Salva、Christine Snedden、Matthew J. Wyvratt、Michael H. Fisher、Peter T. Meinke

  DOI：10.1021/ol025766d

  日期：2002.4.1

  An efficient synthesis of the truncated 3"-aldehyde (3) from nodulisporic acid A (1) under mild conditions is described. Further oxidation of 3 to 3"-carboxylic acid (4) and its subsequent oxidative degradation produced 1"-aldehyde (5). These new derivatives are versatile intermediates for the preparation of new, side chain modified derivatives of nodulisporic acid A. [reaction: see text]

  描述了在温和条件下由结节孢酸A（1）有效合成截短的3“-醛（3）。进一步氧化3至3”-羧酸（4）及其随后的氧化降解生成1“-醛（ 5）。这些新衍生物是多用途中间体，可用于制备结节孢酸A的新侧链改性衍生物。
• Nodulisporic Acid A, a Novel and Potent Insecticide from a <i>Nodulisporium </i>Sp. Isolation, Structure Determination, and Chemical Transformations
  作者：John G. Ondeyka、Gregory L. Helms、Otto D. Hensens、Michael A. Goetz、Deborah L. Zink、Athanasios Tsipouras、Wesley L. Shoop、Lyndia Slayton、Anne W. Dombrowski、Jon D. Polishook、Dan A. Ostlind、Nancy N. Tsou、Richard G. Ball、Sheo B. Singh

  DOI：10.1021/ja971664k

  日期：1997.9.1

  of 1a and its methyl ester, 1b, were independently determined on the basis of ROESY, NOESY, NOEDS, and Jvic evidence. By employing the same methods, the complete relative stereochemistry was determined by analysis of suitable transformation products, using the reduced β-ketodihydropyrrole ring as a stereochemical bridge between the two zones. These results were confirmed by X-ray analysis of the 7-p-bromobenzoate

  从 Nodulisporium sp. 的发酵中分离出强效杀虫剂 nodulisporic acid A (1a)，代表一类新的吲哚萜烯。Nodulisporic acid A 对苍蝇和蚊子的幼虫有亚百万分之一的活性。该结构主要基于对光谱证据的考虑，包括 Dunkel 的计算机化 2D INADEQUATE 分析。1a 及其甲酯 1b 的东半球和西半球的相对立体化学是根据 ROESY、NOESY、NOEDS 和 Jvic 证据独立确定的。通过使用相同的方法，使用还原的 β-酮二氢吡咯环作为两个区域之间的立体化学桥，通过分析合适的转化产物来确定完整的相对立体化学。这些结果通过 7-对溴苯甲酸甲酯衍生物 1c 的 X 射线分析得到证实。绝对立体化学是通过将先进的 Mosher 方法应用于甲基电子...
• Chemical modification of nodulisporic acid A: preliminary structure–activity relationships
  作者：Peter T. Meinke、Michelle B. Ayer、Steven L. Colletti、Chunshi Li、Julie Lim、Dong Ok、Steve Salva、Dennis M. Schmatz、Thomas L. Shih、Wesley L. Shoop、Lynn M. Warmke、Matthew J. Wyvratt、Michelle Zakson-Aiken、Michael H. Fisher

  DOI：10.1016/s0960-894x(00)00469-8

  日期：2000.10

  Medicinal chemistry efforts were initiated to identify the key constituents of the nodulisporic acid A (1) pharmacophore that are integral to its potent insecticidal activity. New semisynthetic derivatives delineated 1 into 'permissive' and 'nonpermissive' regions and led to the discovery of new nodulisporamides with significantly improved flea efficacy. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Discovery of the Development Candidate <i>N</i>-<i>tert</i>-Butyl Nodulisporamide: A Safe and Efficacious Once Monthly Oral Agent for the Control of Fleas and Ticks on Companion Animals
  作者：Peter T. Meinke、Steven L. Colletti、Michael H. Fisher、Matthew J. Wyvratt、Thomas L. Shih、Michelle B. Ayer、Chunshi Li、Julie Lim、Dong Ok、Steve Salva、Lynn M. Warmke、Michelle Zakson、Bruce F. Michael、Pierre deMontigny、Dan A. Ostlind、David Fink、Marlene Drag、Dennis M. Schmatz、Wesley L. Shoop

  DOI：10.1021/jm801334v

  日期：2009.6.11

  Nodulisporic acid A (1) is a structurally complex fungal metabolite that exhibits systemic efficacy against fleas via modulation of an invertebrate specific glutamate-gated ion channel. In order to identify a nodulisporamide suitable for monthly oral dosing in dogs, a library of 335 nodulisporamides was examined in an artificial flea feeding system for intrinsic systemic potency as well as in a mouse/bedbug assay for systemic efficacy and safety. A cohort of 66 nodulisporamides were selected for evaluation in a dog/flea model; pharmacokinetic analysis correlated plasma levels with flea efficacy. These efforts resulted in the identification of the development candidate N-tert-butyl nodulisporamide (3) as a potent and efficacious once monthly oral agent for the control of fleas and ticks on dogs and cats which was directly compared to the topical agents fipronil and imidacloprid, with favorable results obtained. Multidose studies over 3 months confirmed the in vivo ectoparasiticidal efficacy and established that 3 lacked overt mammalian toxicity. Tissue distribution studies in mice using [C-14]-labeled 3 indicate that adipose beds serve as ligand depots, contributing to the long terminal half-lives of these compounds.
• Nodulisporic acid side-Chain modifications: access to the 2″, 3″, 4″, and 6″ registers
  作者：Prasun K. Chakravarty、Thomas L. Shih、Steven L. Colletti、Michelle B. Ayer、Christine Snedden、Howard Kuo、Sriram Tyagarajan、Lynn Gregory、Michelle Zakson-Aiken、Wesley L. Shoop、Dennis M. Schmatz、MatthewJ. Wyvratt、Michael H. Fisher、Peter T. Meinke

  DOI：10.1016/s0960-894x(02)00826-0

  日期：2003.1

  Efficient routes to access the 2", 3", 4", and 6" registers of the nodulisporic acid (NsA) side chain are disclosed. A mild one-carbon, Ph2C=NCH(2)Cequivalent toN mediated homologation of NsA's 3"-aldehyde permitted access to the 4"-register. Curtius reaction of NsA's 3"-acid yielded the corresponding 2"-aldehyde 4 from which the unnatural Delta(2" 3")-olefin isomer 2b was obtained. In addition, Arndt-Eistert reactions of the parent NsA permitted a one-carbon homologation to the 6" register. These efforts identified new analogues with significant flea activity and illustrated the biological significance of unsaturation at the 1",2" register. (C) 2002 Elsevier Science Ltd. All rights reserved.