larixyl diacetate | 4627-51-4

• 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: larixyl diacetate
• 英文别名: (+)-Larixol；[(1S,4S,4aR,8aS)-4-[(3S)-3-acetyloxy-3-methylpent-4-enyl]-4a,8,8-trimethyl-3-methylidene-2,4,5,6,7,8a-hexahydro-1H-naphthalen-1-yl] acetate
• CAS: 4627-51-4
• 化学式: C₂₄H₃₈O₄
• 分子量: 390.563
• InChiKey: CFEOXVWJRPHLSF-QRADPCAZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  醋酸落叶松酯	4-(acetyloxy)-α-ethenyldecahydro-α,5,5,8a-tetramethyl-2-methylene-(αS,1S,4S,4aS,8aR)-1-naphthalenepropanol	4608-49-5	C22H36O3	348.526
  4-(3-乙酰氧基-3-甲基-4-戊烯-1-基)-4A,8,8-三甲基-3-亚甲基十氢-1-萘基乙酸酯	α-ethenyldecahydro-4-hydroxy-α,5,5,8a-tetramethyl-2-methylene-(αS,1S,4S,4aS,8aR)-1-naphthalenepropanol	1438-66-0	C20H34O2	306.489

反应信息

• 作为反应物：
  描述：

  larixyl diacetate 在 双(乙腈)氯化钯(II) 作用下， 以 四氢呋喃 为溶剂， 以86%的产率得到
  参考文献：
  名称：

  Synthesis of ent-crotonadiol and compounds related to it from (+)-larixol

  摘要：

  描述了一种从 6a-acetoxy-14,15-bis-norlabd-8(17)-en13-one 合成 13E-ent-crotonadiol 及其 13Z-isomer 的新方法。13E- 和 13Z-6a- 乙酰氧基赖百当-8(17),13-二烯-15-酸和 13E- 和 13Z-6a- 羟基赖百当-8(17),13-二烯-15-酸的甲酯混合物是由其与三甲基膦酰乙酸酯反应生成的。13E- 和 13Z-6a-hydroxylabd-8(17),13-dien-15-oic acids 的混合物通过水解形成。将这些混合物分离、甲基化并用 LiAlH4 还原后，得到纯净的 13E- 和 13Z- 巴豆二醇，产率分别为 64% 和 16%。从 (+)-larixol 中合成巴豆二醇的两个已知方法被重现。结果表明，它们只生成了 13E-巴豆二醇。

  DOI：

  10.1007/s10600-011-9943-z
• 作为产物：
  描述：

  4-(3-乙酰氧基-3-甲基-4-戊烯-1-基)-4A,8,8-三甲基-3-亚甲基十氢-1-萘基乙酸酯 、 乙酰氯 在 N,N-二甲基苯胺 作用下， 以93%的产率得到larixyl diacetate
  参考文献：
  名称：

  Synthesis of ent-crotonadiol and compounds related to it from (+)-larixol

  摘要：

  描述了一种从 6a-acetoxy-14,15-bis-norlabd-8(17)-en13-one 合成 13E-ent-crotonadiol 及其 13Z-isomer 的新方法。13E- 和 13Z-6a- 乙酰氧基赖百当-8(17),13-二烯-15-酸和 13E- 和 13Z-6a- 羟基赖百当-8(17),13-二烯-15-酸的甲酯混合物是由其与三甲基膦酰乙酸酯反应生成的。13E- 和 13Z-6a-hydroxylabd-8(17),13-dien-15-oic acids 的混合物通过水解形成。将这些混合物分离、甲基化并用 LiAlH4 还原后，得到纯净的 13E- 和 13Z- 巴豆二醇，产率分别为 64% 和 16%。从 (+)-larixol 中合成巴豆二醇的两个已知方法被重现。结果表明，它们只生成了 13E-巴豆二醇。

  DOI：

  10.1007/s10600-011-9943-z

文献信息

• Minor compounds of the oleoroesin of the Kamchatka, Japanese, and Siberian larches
  作者：V. I. Bol'shakova、E. N. Shmidt、V. A. Pentegova、V. I. Mamatyuk

  DOI：10.1007/bf00599256

  日期：1986.9
• Bicyclic labdane diterpenes for use in the treatment of TRPC6 associated diseases
  申请人：Universität Leipzig

  公开号：EP2556829B1

  公开（公告）日：2015-08-19
• Bicyclic Labdane Diterpenes for Use in the Treatment of TRPC6 Associated Diseases
  申请人：Schaefer Michael

  公开号：US20140309300A1

  公开（公告）日：2014-10-16

  The present invention relates to bicyclic labdane diterpenes for use in the treatment of a disease associated with activation of transient receptor potential cation channel 6 (TRPC6), preferably a pulmonary or a renal disease. In one aspect the invention relates to the use of a bicyclic labdane diterpene for blocking calcium transport via TRPC6. Another aspect of the invention is a bicyclic labdane diterpene according to formula (1) for use as a medicament wherein R 1 is selected from hydrogen and C 1 to C 4 acyl, wherein the bicyclic labdane diterpene optionally comprises at least one double bond between the carbon atoms at positions 1 and 2, 2 and 3, 5 and 6, 6 and 7 and/or 14 and 15, wherein the carbon atoms at positions 1, 2, 3, 7, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 are connected to hydrogen atoms or comprise at least one substitution.
• Pharmacological inhibition of focal segmental glomerulosclerosis-related, gain of function mutants of TRPC6 channels by semi-synthetic derivatives of larixol
  作者：Nicole Urban、Sonja Neuser、Anika Hentschel、Sebastian Köhling、Jörg Rademann、Michael Schaefer

  DOI：10.1111/bph.13977

  日期：2017.11

  Background and PurposeGain of function mutations in TRPC6 channels can cause autosomal dominant forms of focal segmental glomerulosclerosis (FSGS). Validated inhibitors of TRPC6 channels that are biologically active on FSGS‐related TRPC6 mutants are eagerly sought.Experimental ApproachWe synthesized new TRPC6‐inhibiting modulators from larixol, a resiniferous constituent of Larix decidua, and tested the potency and selectivity in cell lines stably expressing various TRPC channel isoforms. Channel activation was followed by Ca2+ influx analyses and electrophysiological recordings. The most promising compound larixyl carbamate (LC) was tested on native TRPC6 channels and TRPC6 constructs carrying FSGS‐related point mutations.Key ResultsLC exhibited an about 30‐fold preference for TRPC6 over TRPC3 channels and a fivefold preference for TRPC6 over TRPC7 channels. Six FSGS‐related TRPC6 mutants, including the highly active M132T and R175Q variants, were strongly inhibited by 1 μM LC. Surprisingly, no TRPC6‐related Ca2+ signals were detectable in primary murine podocytes, or in acutely isolated glomeruli. in these preparations. Quantitative PCR revealed a 20‐fold to 50‐fold lower abundance of TRPC6 transcripts in rat or mouse podocytes, compared with pulmonary artery smooth muscle cells from the same species. Accordingly, electrophysiological recordings demonstrated that DAG‐induced currents in murine podocytes are very small, but sensitive to LC.Conclusions and ImplicationsIn spite of their low abundance in native podocytes, native TRPC6 channels are targetable using larixol‐derived TRPC6 inhibitors. As observed with wild‐type TRPC6 channels, FSGS‐related TRPC6 mutants were sensitive to the newly developed inhibitors, paving the way for experimental therapies.
• Synthesis of ent-crotonadiol and compounds related to it from (+)-larixol
  作者：P. F. Vlad、A. Chokyrlan、M. D’Ambrosio、M. N. Koltsa、A. N. Barba、K. Edu、A. Byryyak、A. Nikolescu、A. Mari、K. Deleanu

  DOI：10.1007/s10600-011-9943-z

  日期：2011.7

  A new synthesis of 13E-ent-crotonadiol and its 13Z-isomer from 6a-acetoxy-14,15-bis-norlabd-8(17)-en13-one is described. A mixture of methyl esters of 13E- and 13Z-6a-acetoxylabd-8(17),13-dien-15-oic and 13E- and 13Z-6a-hydroxylabd-8(17),13-dien-15-oic acids was formed by its reaction with trimethylphosphonoacetate. Mixtures of 13E- and 13Z-6a-hydroxylabd-8(17),13-dien-15-oic acids were formed by hydrolysis of this mixture. These were separated, methylated, and reduced by LiAlH4 to give the pure 13E- and 13Z-crotonadiols in 64 and 16% yields, respectively. The two known syntheses of crotonadiol from (+)-larixol were reproduced. It was shown that they produced only 13E-crotonadiol.

  描述了一种从 6a-acetoxy-14,15-bis-norlabd-8(17)-en13-one 合成 13E-ent-crotonadiol 及其 13Z-isomer 的新方法。13E- 和 13Z-6a- 乙酰氧基赖百当-8(17),13-二烯-15-酸和 13E- 和 13Z-6a- 羟基赖百当-8(17),13-二烯-15-酸的甲酯混合物是由其与三甲基膦酰乙酸酯反应生成的。13E- 和 13Z-6a-hydroxylabd-8(17),13-dien-15-oic acids 的混合物通过水解形成。将这些混合物分离、甲基化并用 LiAlH4 还原后，得到纯净的 13E- 和 13Z- 巴豆二醇，产率分别为 64% 和 16%。从 (+)-larixol 中合成巴豆二醇的两个已知方法被重现。结果表明，它们只生成了 13E-巴豆二醇。