Spirolaxine
目录号 : GC40963
A phthalide antibacterial agent
Cas No.:126382-01-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Spirolaxine is a long-chain phthalide produced by the fungus S. laxum that has antibacterial properties. Spirolaxine is a potent anti-H. pylori agent (MIC = 0.2 µg/cm3) with weak activity against E. coli. Spirolaxine (1-40 µM) inhibits proliferation of endothelial (BMEC, HUVEC) and tumor (LoVo, HL-60) cells in culture. B. megaterium and C. echinulate produce hydroxylated metabolites of spirolaxine when given spirolaxine as a substrate.
| Cas No. | 126382-01-2 | SDF | |
| Canonical SMILES | OC1=CC(OC)=C(C(O[C@@H]2CCCCC[C@@H]3CCC[C@]4(CC[C@@H](C)O4)O3)=O)C2=C1 | ||
| 分子式 | C23H32O6 | 分子量 | 404.5 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4722 mL | 12.3609 mL | 24.7219 mL |
| 5 mM | 0.4944 mL | 2.4722 mL | 4.9444 mL |
| 10 mM | 0.2472 mL | 1.2361 mL | 2.4722 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Identification of a type III polyketide synthase involved in the biosynthesis of Spirolaxine
Appl Microbiol Biotechnol 2016 Aug;100(16):7103-13.PMID:27023915DOI:10.1007/s00253-016-7444-5.
Spirolaxine is a natural product isolated from Sporotrichum laxum ATCC 15155, which has shown a variety of biological activities including promising anti-Helicobacter pylori property. To understand how this compound is biosynthesized, the genome of S. laxum was sequenced. Analysis of the genome sequence revealed two putative type III polyketide synthase (PKS) genes in this strain, Sl-pks1 and Sl-pks2, which are located adjacent to each other (~2.0 kb apart) in a tail-to-tail arrangement. Disruption of these two genes revealed that Sl-PKS2 is the dedicated PKS involved in the biosynthesis of Spirolaxine. The intron-free Sl-pks2 gene was amplified from the cDNA of S. laxum and ligated into the expression vector pET28a for expression in Escherichia coli BL21-CodonPlus (DE3)-RIL. The major products of Sl-PKS2 in E. coli were characterized as alkylresorcinols that contain a C13-C17 saturated or unsaturated hydrocarbon side chain based on the spectral data. This enzyme was purified and reacted with malonyl-CoA and a series of fatty acyl-SNACs (C6-C10). Corresponding alkylresorcinols were formed from the decarboxylation of the synthesized tetraketide resorcylic acids, together with fatty acyl-primed triketide and tetraketide pyrones as byproducts. This work provides important information about the PKS involved in the biosynthesis of Spirolaxine, which will facilitate further understanding and engineering of the biosynthetic pathway of this medicinally important molecule.
Anti-Helicobacter pylori activity of derivatives of the phthalide-containing antibacterial agents Spirolaxine methyl ether, CJ-12,954, CJ-13,013, CJ-13,102, CJ-13,104, CJ-13,108 and CJ-13,015
Bioorg Med Chem 2008 Jun 1;16(11):6179-85.PMID:18457954DOI:10.1016/j.bmc.2008.04.037.
The naturally occurring phthalide-containing antibiotics Spirolaxine methyl ether, CJ-12,954, CJ-13,013, CJ-13,015, CJ-13,102, CJ-13,103, CJ-13,104 and CJ-13,108, have been reported to exhibit anti-H. pylori activity. However, the exact stereochemistry of Spirolaxine methyl ether, CJ-12,954 or CJ-13,013, contributing to this observed activity has not been confirmed. The anti-H. pylori activity of several analogues of Spirolaxine methyl ether, CJ-12,954 and CJ-13,013 of defined stereochemistry together with the anti-H. pylori activity of several indole analogues of the simpler phthalide-containing antibiotics CJ-13,102, CJ-13,104, CJ-13,108 and CJ-13,015 is reported herein. A 1:1 mixture of spiroacetals 5b and 6b in which the phthalide substituent exhibited (3R)-stereochemistry was sixty times more active than the corresponding 1:1 mixture of spiroacetals with (3S)-stereochemistry. Notably, the unnatural (2''S)-diastereomer of Spirolaxine methyl ether exhibited more potent anti-H. pylori activity than the natural product Spirolaxine methyl ether. The 4,6-dimethoxyindoles 9, 10, 11 and 13 were all found to be less active than their parent compounds 1, 2, 3 and 4, respectively. Chain-shortened 4,6-dimethoxyindole analogue 12 of CJ-13,108 3 and 4,6-dimethoxyindole-spiroacetal 13 exhibited weak anti-H. pylori activity thus providing future opportunity for drug discovery programs.
Synthesis of the anti-Helicobacter pylori agent (+)-spirolaxine methyl ether and the unnatural (2"S)-diastereomer
Org Biomol Chem 2007 Aug 21;5(16):2572-82.PMID:18019531DOI:10.1039/b708265g.
The first enantioselective synthesis of the anti-Heliocbacter pylori agent (+)-spirolaxine methyl ether 2b has been carried out in a convergent fashion establishing that the absolute stereochemistry of the natural product is in fact (3R, 2"R, 5"R, 7"R) after initial synthesis of the unnatural (2"S)-diastereomer 2a. The key step in the synthesis of (+)-spirolaxine methyl ether 2b involved a heterocycle-activated Julia-Kocienski olefination between benzothiazole-based spiroacetal sulfone 4b and phthalide aldehyde 3a. (2"R, 5"S, 7"S)-Spiroacetal sulfone 4b was prepared via cyclisation of protected dihydroxyketone 6b, which in turn was derived from the coupling of the acetylide derived from (R)-acetylene 24b with aldehyde 3a. Phthalide aldehyde 3a was prepared via intramolecular acylation of bromocarbamate 15, which was available via titanium tetrafluoride-(+)-BINOL-mediated allylation of 3,5-dimethoxybenzaldehyde 13. Union of the sulfone 4b and aldehyde 3a fragments successfully completed the enantioselective synthesis of (+)-spirolaxine methyl ether 2b. The synthesis of the unnatural (3R, 2"S, 5"R, 7"R)-diastereomer of Spirolaxine methyl ether 2a was also undertaken in a similar manner by union of phthalide aldehyde 3a with (2"S, 5"S, 7"S)-spiroacetal sulfone 4a derived from (S)-acetylene 24a.
Microbial transformation of Spirolaxine, a bioactive undecaketide fungal metabolite from the basidiomycete Sporotrichum laxum
Chem Biodivers 2007 Dec;4(12):2772-9.PMID:18081087DOI:10.1002/cbdv.200790226.
Incubation of (+)-spirolaxine (= (3R)-5-hydroxy-7-methoxy-3-{5-[(2R,5R,7R)-2-methyl-1,6-dioxaspiro[4.5]dec-7-yl]pentyl}-2-benzofuran-1(3H)-one; 1a) with Bacillus megaterium afforded two new mono- and one new dihydroxylated metabolite(s), all OH groups being introduced on the non-activated six-membered ring. In contrast, exposure of 1a to Cunninghamella echinulata gave rise to hydroxylation on the five-membered ring of the parent structure. The structures and absolute configurations of the new products 1b-e were deduced on the basis of MS and NMR data. The metabolite 1b was investigated, in comparison to 1a, for its cytotoxicity (sulforhodamin-B test) and for its antiproliferative activity towards bovine microvascular endothelial cells (BMEC).
Three new resorcylic acid derivatives from Sporotrichum laxum
Bioorg Med Chem Lett 2013 Nov 1;23(21):5806-9.PMID:24070784DOI:10.1016/j.bmcl.2013.08.109.
Sporotrichum laxum ATCC 15155 is the producing strain of the potent anti-Helicobacter pylori natural product Spirolaxine (1). Investigation of the secondary metabolites in this fungus led to the isolation of five phthalides (1, 2, 3, 6 and 9) and five resorcylic acid derivatives (4, 5, 7, 8 and 10), among which 5, 7 and 8 are new compounds. The structures were elucidated by spectroscopic analyses, and the absolute configurations of 7 and 8 were determined by Mosher's method. Addition of soy flour into the potato dextrose agar has led to the increased production of 4-10. A biosynthetic pathway consisting of a highly reducing polyketide synthase (PKS), a nonreducing PKS and a series of tailoring enzymes was proposed to produce these fungal natural products. The resorcylic acid derivatives are proposed to result from early hydrolysis of the polyketide chain or incorporation of a longer fatty acyl starter unit.