Dihydroartemisinic acid
(Synonyms: 双氢青蒿酸; Dihydroqinghao acid) 目录号 : GC38429
A precursor to artemisinin
Cas No.:85031-59-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Dihydroartemisinic acid is a biosynthetic precursor to the antimalarial agent artemisinin and an intermediate in the synthesis of artemisinin from artemisinic acid .1,2
1.Tian, N., Li, J., Liu, S., et al.Simultaneous isolation of artemisinin and its precursors from Artemisia annua L. by preparative RP-HPLCBiomed. Chromatogr.26(6)708-713(2012) 2.Roth, R.J., and Acton, N.A simple conversion of artemisinic acid into artemisininJ. Nat. Prod.52(5)1183-1185(1989)
| Cas No. | 85031-59-0 | SDF | |
| 别名 | 双氢青蒿酸; Dihydroqinghao acid | ||
| Canonical SMILES | OC([C@@H]([C@@]1([H])[C@]2([H])[C@](CCC(C)=C2)([H])[C@H](C)CC1)C)=O | ||
| 分子式 | C15H24O2 | 分子量 | 236.35 |
| 溶解度 | DMF: 20 mg/ml,DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml,DMSO: 10 mg/ml,Ethanol: 16 mg/ml | 储存条件 | 4°C, protect from light |
| 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 | 4.231 mL | 21.1551 mL | 42.3101 mL |
| 5 mM | 0.8462 mL | 4.231 mL | 8.462 mL |
| 10 mM | 0.4231 mL | 2.1155 mL | 4.231 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。
Autoxidation of a C2-Olefinated Dihydroartemisinic acid Analogue to Form an Aromatic Ring: Application to Serrulatene Biosynthesis
J Nat Prod 2022 Apr 22;85(4):951-962.PMID:35357832DOI:10.1021/acs.jnatprod.1c01101.
Dihydroartemisinic acid (DHAA) is a plant natural product that undergoes a spontaneous endoperoxide-forming cascade reaction to yield artemisinin in the presence of air. The endoperoxide functional group gives artemisinin its biological activity that kills Plasmodium falciparum, the parasite that causes malaria. To enhance our understanding of the mechanism of this cascade reaction, 2,3-didehydrodihydroartemisinic acid (2,3-didehydro-DHAA), a DHAA derivative with a double bond at the C2-position, was synthesized. When 2,3-didehydro-DHAA was exposed to air over time, instead of forming an endoperoxide, this compound predominantly underwent aromatization. This olefinated DHAA analogue reveals the requirement of a monoalkene functional group to initiate the endoperoxide-forming cascade reaction to yield artemisinin from DHAA. In addition, this aromatization process was exploited to illustrate the autoxidation process of a different plant natural product, dihydroserrulatene, to form the aromatic ring in serrulatene. This spontaneous aromatization process has applications in other natural products such as leubethanol and erogorgiaene. Due to their similarity in structure to antimicrobial natural products, the synthesized compounds in this study were tested for biological activity. A group of the tested compounds had minimum inhibitory concentration (MIC) values ranging from 12.5 to 25 μg/mL against the bacterial pathogen Staphylococcus aureus and the fungal pathogen Cryptococcus neoformans.
Synthesis of amorpha-4,11-diene from Dihydroartemisinic acid
Tetrahedron 2019 Feb 8;75(6):743-748.PMID:30739959DOI:10.1016/j.tet.2018.12.050.
Amorphadiene is a natural product involved in the biosynthesis of the antimalarial drug artemisinin. A convenient four-step synthesis of amorphadiene, starting from commercially available Dihydroartemisinic acid, is reported. The targeted molecule is isolated with an overall yield of 85% on a multi-gram scale in four steps with only one chromatography.
Multienzyme Biosynthesis of Dihydroartemisinic acid
Molecules 2017 Aug 28;22(9):1422.PMID:28846664DOI:10.3390/molecules22091422.
One-pot multienzyme biosynthesis is an attractive method for producing complex, chiral bioactive compounds. It is advantageous over step-by-step synthesis, as it simplifies the process, reduces costs and often leads to higher yield due to the synergistic effects of enzymatic reactions. In this study, Dihydroartemisinic acid (DHAA) pathway enzymes were overexpressed in Saccharomyces cerevisiae, and whole-cell biotransformation of amorpha-4,11-diene (AD) to DHAA was demonstrated. The first oxidation step by cytochrome P450 (CYP71AV1) is the main rate-limiting step, and a series of N-terminal truncation and transcriptional tuning improved the enzymatic activity. With the co-expression of artemisinic aldehyde dehydrogenase (ALDH1), which recycles NADPH, a significant 8-fold enhancement of DHAA production was observed. Subsequently, abiotic conditions were optimized to further enhance the productivity of the whole-cell biocatalysts. Collectively, approximately 230 mg/L DHAA was produced by the multi-step whole-cell reaction, a ~50% conversion from AD. This study illustrates the feasibility of producing bioactive compounds by in vitro one-pot multienzyme reactions.
Synthesis of [3,3-2H2]-Dihydroartemisinic Acid to Measure the Rate of Nonenzymatic Conversion of Dihydroartemisinic acid to Artemisinin
J Nat Prod 2020 Jan 24;83(1):66-78.PMID:31859509DOI:10.1021/acs.jnatprod.9b00686.
Dihydroartemisinic acid is the biosynthetic precursor to artemisinin, the endoperoxide-containing natural product used to treat malaria. The conversion of Dihydroartemisinic acid to artemisinin is a cascade reaction that involves C-C bond cleavage, hydroperoxide incorporation, and polycyclization to form the endoperoxide. Whether or not this reaction is enzymatically controlled has been controversial. A method was developed to quantify the nonenzymatic conversion of Dihydroartemisinic acid to artemisinin using LC-MS. A seven-step synthesis of 3,3-dideuterodihydroartemisinic acid (23) was accomplished beginning with Dihydroartemisinic acid (1). The nonenzymatic rates of formation of 3,3-dideuteroartemisinin (24) from 3,3-dideuterodihydroartemisinic acid (23) were 1400 ng/day with light and 32 ng/day without light. Moreover, an unexpected formation of nondeuterated artemisinin (3) from 3,3-dideuterodihydroartemisinic acid (23) was detected in both the presence and absence of light. This formation of nondeuterated artemisinin (3) from its dideuterated precursor (23) suggests an alternative mechanistic pathway that operates independent of light to form artemisinin, involving the loss of the two C-3 deuterium atoms.
Metabolic Engineering of Saccharomyces cerevisiae for Enhanced Dihydroartemisinic acid Production
Front Bioeng Biotechnol 2020 Mar 17;8:152.PMID:32258005DOI:10.3389/fbioe.2020.00152.
Direct bioproduction of DHAA (Dihydroartemisinic acid) rather than AA (artemisinic acid), as suggested by previous work would decrease the cost of semi-biosynthesis artemisinin by eliminating the step of initial hydrogenation of AA. The major challenge in microbial production of DHAA is how to efficiently manipulate consecutive key enzymes ADH1 (artemisinic alcohol dehydrogenase), DBR2 [artemisinic aldehyde Δ11(13) reductase] and ALDH1 (aldehyde dehydrogenase) to redirect metabolic flux and elevate the ratio of DHAA to AA (artemisinic acid). Herein, DHAA biosynthesis was achieved in Saccharomyces cerevisiae by introducing a series of heterologous enzymes: ADS (amorpha-4,11-diene synthase), CYP71AV1 (amorphadiene oxidase), ADH1, DBR2 and ALDH1, obtaining initial DHAA/AA ratio at 2.53. The flux toward DHAA was enhanced by pairing fusion proteins DBR2-ADH1 and DBR2-ALDH1, leading to 1.75-fold increase in DHAA/AA ratio (to 6.97). Moreover, to promote the substrate preference of ALDH1 to dihydroartemisinic aldehyde (the intermediate for DHAA synthesis) over artemisinic aldehyde (the intermediate for AA synthesis), two rational engineering strategies, including downsizing the active pocket and enhancing the stability of enzyme/cofactor complex, were proposed to engineer ALDH1. It was found that the mutant H194R, which showed better stability of the enzyme/NAD+ complex, obtained the highest DHAA to AA ratio at 3.73 among all the mutations. Then the mutant H194R was incorporated into above rebuilt fusion proteins, resulting in the highest ratio of DHAA to AA (10.05). Subsequently, the highest DHAA reported titer of 1.70 g/L (DHAA/AA ratio of 9.84) was achieved through 5 L bioreactor fermentation. The study highlights the synergy of metabolic engineering and protein engineering in metabolic flux redirection to get the most efficient product to the chemical process, and simplified downstream conversion process.