Tropinone
(Synonyms: 托品酮) 目录号 : GC39118
A tropane
Cas No.:532-24-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tropinone is a polyketide synthase-derived tropane that has been found in A. belladonna.1,2,3 It is a central intermediate in the biosynthesis of various tropane alkaloids, including (–)-hyoscyamine , (+)-hyoscyamine, scopolamine, atropine , and cocaine.
1.Bedewitz, M.A., Jones, A.D., D'Auria, J.C., et al.Tropinone synthesis via an atypical polyketide synthase and P450-mediated cyclizationNat. Commun.9(1)5281(2018) 2.Piechowska, K., Mizerska-Kowalska, M., Zdzisińska, B., et al.Tropinone-derived alkaloids as potent anticancer agents: Synthesis, tyrosinase inhibition, mechanism of action, DFT calculation, and molecular docking studiesInt. J. Mol. Sci.21(23)9050(2020) 3.Majewski, M., and Lazny, R.Synthesis of tropane alkaloids via enantioselective deprotonation of tropinoneJ. Org. Chem.60(18)5825–5830(1995)
| Cas No. | 532-24-1 | SDF | |
| 别名 | 托品酮 | ||
| Canonical SMILES | O=C1CC(N2C)CCC2C1 | ||
| 分子式 | C8H13NO | 分子量 | 139.19 |
| 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 | 7.1844 mL | 35.9221 mL | 71.8442 mL |
| 5 mM | 1.4369 mL | 7.1844 mL | 14.3688 mL |
| 10 mM | 0.7184 mL | 3.5922 mL | 7.1844 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。
Tropinone reductases, enzymes at the branch point of tropane alkaloid metabolism
Phytochemistry 2006 Feb;67(4):327-37.PMID:16426652DOI:10.1016/j.phytochem.2005.12.001.
Two stereospecific oxidoreductases constitute a branch point in tropane alkaloid metabolism. Products of tropane metabolism are the alkaloids hyoscyamine, scopolamine, cocaine, and polyhydroxylated nortropane alkaloids, the calystegines. Both Tropinone reductases reduce the precursor Tropinone to yield either tropine or pseudotropine. In Solanaceae, tropine is incorporated into hyoscyamine and scopolamine; pseudotropine is the first specific metabolite on the way to the calystegines. Isolation, cloning and heterologous expression of both Tropinone reductases enabled kinetic characterisation, protein crystallisation, and structure elucidation. Stereospecificity of reduction is achieved by binding Tropinone in the respective enzyme active centre in opposite orientation. Immunolocalisation of both enzyme proteins in cultured roots revealed a tissue-specific protein accumulation. Metabolite flux through both arms of the tropane alkaloid pathway appears to be regulated by the activity of both enzymes and by their access to the precursor Tropinone. Both Tropinone reductases are NADPH-dependent short-chain dehydrogenases with amino acid sequence similarity of more than 50% suggesting their descent from a common ancestor. Putative Tropinone reductase sequences annotated in plant genomes other that Solanaceae await functional characterisation.
Tropinone synthesis via an atypical polyketide synthase and P450-mediated cyclization
Nat Commun 2018 Dec 11;9(1):5281.PMID:30538251DOI:10.1038/s41467-018-07671-3.
Tropinone is the first intermediate in the biosynthesis of the pharmacologically important tropane alkaloids that possesses the 8-azabicyclo[3.2.1]octane core bicyclic structure that defines this alkaloid class. Chemical synthesis of Tropinone was achieved in 1901 but the mechanism of Tropinone biosynthesis has remained elusive. In this study, we identify a root-expressed type III polyketide synthase from Atropa belladonna (AbPYKS) that catalyzes the formation of 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This catalysis proceeds through a non-canonical mechanism that directly utilizes an unconjugated N-methyl-Δ1-pyrrolinium cation as the starter substrate for two rounds of malonyl-Coenzyme A mediated decarboxylative condensation. Subsequent formation of Tropinone from 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid is achieved through cytochrome P450-mediated catalysis by AbCYP82M3. Silencing of AbPYKS and AbCYP82M3 reduces tropane levels in A. belladonna. This study reveals the mechanism of Tropinone biosynthesis, explains the in planta co-occurrence of pyrrolidines and tropanes, and demonstrates the feasibility of tropane engineering in a non-tropane producing plant.
Characterization of a putative Tropinone reductase from Tarenaya hassleriana with a broad substrate specificity
Biotechnol Appl Biochem 2022 Dec;69(6):2530-2539.PMID:34902878DOI:10.1002/bab.2302.
A novel short-chain alcohol dehydrogenase from Tarenaya hassleriana labeled as putative Tropinone reductase was heterologously expressed in Escherichia coli. Purified recombinant protein had molecular weight of approximately 30 kDa on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. T. hassleriana Tropinone reductase-like enzyme (ThTRL) had not detected oxidative activity. The optimum pH for enzyme activity of ThTRL was weakly acidic (pH 5.0). 50°C was the optimum temperature for ThTRL. The highest catalytic efficiency and substrate affinity for recombinant ThTRL were observed with (+)-camphorquinone (kcat /Km = 814.3 s-1 mM-1 , Km = 44.25 μM). ThTRL exhibited a broad substrate specificity and reduced various carbonyl compounds, including small lipophilic aldehydes and ketones, terpene ketones, and their structural analogs.
Synthesis and Cytotoxicity Evaluation of Tropinone Derivatives
Nat Prod Bioprospect 2017 Apr;7(2):215-223.PMID:28321792DOI:10.1007/s13659-017-0124-z.
Sixteen Tropinone derivatives were prepared, and their antitumor activities against five human cancer cells (HL-60, A-549, SMMC-7721, MCF-7 and SW480) were evaluated with MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy methoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium] assay. Most of the derivatives exhibited better activities compared with Tropinone at the concentration of 40 μM. Particularly, derivative 6 showed significant activities with IC50 values of 3.39, 13.59, 6.65, 13.09 and 12.38 μM respectively against HL-60, A-549, SMMC-7721, MCF-7 and SW480 cells, which suggested more potent activities than that of cis-dichlorodiamineplatinum (DDP).
Substrate flexibility and reaction specificity of Tropinone reductase-like short-chain dehydrogenases
Bioorg Chem 2014 Apr;53:37-49.PMID:24583623DOI:10.1016/j.bioorg.2014.01.004.
Annotations of protein or gene sequences from large scale sequencing projects are based on protein size, characteristic binding motifs, and conserved catalytic amino acids, but biochemical functions are often uncertain. In the large family of short-chain dehydrogenases/reductases (SDRs), functional predictions often fail. Putative Tropinone reductases, named Tropinone reductase-like (TRL), are SDRs annotated in many genomes of organisms that do not contain tropane alkaloids. SDRs in vitro often accept several substrates complicating functional assignments. Cochlearia officinalis, a Brassicaceae, contains tropane alkaloids, in contrast to the closely related Arabidopsis thaliana. TRLs from Arabidopsis and the Tropinone reductase isolated from Cochlearia (CoTR) were investigated for their catalytic capacity. In contrast to CoTR, none of the Arabidopsis TRLs reduced Tropinone in vitro. NAD(H) and NADP(H) preferences were relaxed in two TRLs, and protein homology models revealed flexibility of amino acid residues in the active site allowing binding of both cofactors. TRLs reduced various carbonyl compounds, among them terpene ketones. The reduction was stereospecific for most of TRLs investigated, and the corresponding terpene alcohol oxidation was stereoselective. Carbonyl compounds that were identified to serve as substrates were applied for modeling pharmacophores of each TRL. A database of commercially available compounds was screened using the pharmacophores. Compounds identified as potential substrates were confirmed by turnover in vitro. Thus pharmacophores may contribute to better predictability of biochemical functions of SDR enzymes.