2738-64-9

Basic information

• Product Name: PIERICIDIN A
• Synonyms: ,5,7,11-tetramethyl-,(all-e)-(4s,5s)-;2,6,9,11-tridecatetraen-4-ol,13-(4-hydroxy-5,6-dimethoxy-3-methyl-2-pyridyl)-3;piericidin;piericidin(sub1);piericidinea;SN 198E;SHAOGUAMYCIN B;SHAOGUANMYCIN B
• CAS NO: 2738-64-9
• Molecular Formula: C₂₅H₃₇NO₄
• Molecular Weight: 415.57
• Product Categories: Antibiotic
• Mol File: 2738-64-9.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 591.7oC at 760 mmHg。 产品描述 安全性：
• Flash Point: 85 °C
• Appearance: green-yellow/liquid
• Density: 1.05 g/cm3
• Vapor Pressure: 1.83E-16mmHg at 25°C
• Refractive Index: 1.533
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 20 mg/ml).
• PKA: 5.21±0.33(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or Ethanol may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: PIERICIDIN A(CAS DataBase Reference)
• NIST Chemistry Reference: PIERICIDIN A(2738-64-9)
• EPA Substance Registry System: PIERICIDIN A(2738-64-9)

Safety Data

• Hazard Codes: T+,Xn
• Statements: 26/27/28-20/21/22
• Safety Statements: 28-36/37-45
• RIDADR: UN 3382 6.1/PG 1
• WGK Germany: 3
• RTECS: YD4588000
• F: 3-10
• Hazardous Substances Data: 2738-64-9(Hazardous Substances Data)

Usage

Description

Piericidin A (2738-64-9) is a potent inhibitor of the mitochondrial and bacterial type I NADH-ubiquinone oxidoreductase (complex I).1?Piericidin A is a ubiquinone analog which binds to the ubiquinone binding site of the enzyme.2?It is an extremely useful tool for exploring the role of complex I in mitochondrial function in both normal and pathophysiology.3-5?Prevents upregulation of GRP78 and induces cell death in glucose-deprived, etoposide-resistant HT-29 cells (IC50=7.7 nM).6

Uses

Different sources of media describe the Uses of 2738-64-9 differently. You can refer to the following data:
1. Piericidin A is the major analogue of a family of pyridyl antibiotics isolated from selected Streptomyces species. It is a specific, potent inhibitor of NADH-ubiquinone oxidoreductase (Complex I) that binds to ubiquinone binding site(s). Piericidin A inhibits both mitochondrial and bacterial NADH-ubiquinone oxidoreductases, binding close to NUOD-NUOB interface.
2. Piericidin A is an antibiotic and a member of the Class I inhibitors that acts as an effective inhibitor of Complex I.

Biochem/physiol Actions

Piericidin A (PA), an insecticidal metabolite of Streptomyces mobaraensis is a potential quorum-sensing inhibitors (QSIs) that can destroy the expression of the virulence genes of Erwinia carotovora subsp. atroseptica (Eca). Hence it may be used as control agents of soft rot disease on potato tubers.

in vitro

previous study found that piericidin a could inhibit the electron transport system at two sites. piericidin a specifically reacted at very low concentrations at a site near the reduced nadh dehydrogenase. at high concentrations, piericidin a inhibited the succinic dehydrogenase system, and the inhibition could be partially reversed by coenzyme q. moreover, it was found that both the succinate and nadh oxidase system were inhibited at high levels of piericidin a [1].

in vivo

animal study was performed to evaluate the effect of piericidin a and antagonistic effect of vitamin k3 on respiration, blood pressure and heart rate in rats. results showed that 0.167 mg/kg of piericidin a increased the respiratory rate and the lowered blood pressure rapidly. furthermore, vitamin k3 (10-40 mg/kg) could restore the responses to piericidin a in rats [2].

Enzyme inhibitor

This reduced antibiotic (FW = 423.64 g/mol; CAS 2738-64-9; Soluble in ethanol, methanol, DMF or DMSO) is a structural analogue of ubiquinone and a partially competitive inhibitor of bacterial and mitochondrial Type-I NADH-ubiquinone oxidoreductases (or Complex I). Octahydropiericidin A also inhibits glucose dehydrogenase.

References

1) Fato?et al.?(2009),?Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species; Biochim. Biophys. Acta,?1787?384 2) Zhou and Fenical (2016),?The unique chemistry and biology of the piericidins; J. Antibiot. (Tokyo),?69?582 3) Bongard?et al.?(2015),?The effects of mitochondrial complex I blockade on ATP and permeability in rat pulmonary microvascular endothelial cells in culture (PMVEC) are overcome by coenzyme Q1 (CoQ1); Free Radic. Biol. Med.,?79?69 4) Lee?et al.?(2013),?Isoniazid-induced cell death is precipitated by underlying mitochondrial complex I dysfunction in mouse hepatocytes; Free Radic. Biol. Med.,?65?584 5) Choi?et al.?(2011),?Loss of mitochondrial complex I activity potentiates dopamine neuron death induced by microtubule dysfunction in a parkinson’s disease model; J. Cell Biol.,?192?873 6) Hwang?et al.?(2008),?Etoposide-resistant HT-29 human colon carcinoma cells during glucose deprivation are sensitive to piericidin A, a GRP78 down regulator; J. Cell Physiol.,?215?243

InChI:InChI=1/C25H37NO4/c1-9-18(4)22(27)19(5)15-17(3)12-10-11-16(2)13-14-21-20(6)23(28)24(29-7)25(26-21)30-8/h9-10,12-13,15,19,22,27H,11,14H2,1-8H3,(H,26,28)/b12-10+,16-13+,17-15+,18-9+/t19-,22+/m1/s1

Upstream product

• 1112068-20-8 C₁₆H₁₉NO₄ 
• 609-14-3 2-acetylpropanoic acid ethyl ester 
• 936482-98-3 (2E,4R,5R)-4-(tert-butyldimethylsilyloxy)-3,5-dimethyl-2-octen-6-yn 
• 131622-62-3 piericidin A₁ 3′-O-6-deoxy-α-L-talopyranoside 
• 78592-73-1 (E)-4-iodo-3-methylbut-3-en-1-ol 
• 134833-58-2 (2E,4R,5R,6E)-5-(tert-butyldimethylsilyloxy)-2,4,6-trimethylocta-2,6-dien-1-ol 
• 134833-55-9 (E)-(2S,3R)-3-(tert-butyldimethylsilanyloxy)-2,4-dimethyl-hex-4-enal 
• 134833-54-8 (2R,3R,E)-3-(tert-butyldimethylsilyloxy)-2,4-dimethylhex-4-en-1-ol 
• 50331-71-0 ethyl 3-methyl-2-oxobut-3-enoate 
• 497-03-0 2-methylbut-2-enal 
• 912877-21-5 (R)-4-benzyl-3-((2S,3R,E)-3-(tert-butyldimethylsilyloxy)-2,4-dimethylhex-4-enoyl)oxazolidin-2-one 
• 912877-19-1 (R)-4-benzyl-3-((2S,3R,E)-3-hydroxy-2,4-dimethylhex-4-enoyl)oxazolidin-2-one 

Downstream Products

• 5085-85-8 2-((2E,5E,7E,11E)-(9R,10S)-10-Hydroxy-3,7,9,11-tetramethyl-trideca-2,5,7,11-tetraenyl)-5,6-dimethoxy-3-methyl-pyridin-4-ol 

Relevant articles and documents

Propene as an Atom-Economical Linchpin for Concise Total Synthesis of Polyenes: Piericidin A

A concise and convergent total synthesis of piericidin A is disclosed. The synthesis hinges on the utilization of propene as a synthetic linchpin to merge the properly elaborated alkyne fragments, leading to the 1,3,6-triene motif of piericidin A. Utilization of propene as a unique alkene, capable of sequential coupling with two alkynes, is further illustrated in the context of various 1,3,6-triene products. The latter process proceeds with high atom economy and efficiently gives rise to complex frameworks from readily accessible alkyne substrates. This strategic C-C bond formation offers an orthogonal paradigm in the design of synthetic routes, leading to higher step economy and more efficient syntheses of polyunsaturated natural products.

Total synthesis of piericidin A1. application of a modified negishi carboalumination-nickel-catalyzed cross-coupling

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Total synthesis of piericidin A1 and B1 and key analogues

Full details of the total synthesis of piericidin A1 and B1 and its extension to the preparation of a series of key analogues are described including ent-piericidin A1 (ent-1), 4′-deshydroxypiericidin A1 (58), 5′-desmethylpiericidin A1 (73), 4′-deshydroxy-5′- desmethylpiericidin A1 (75), and the corresponding analogues 51, 59, 76, and 77 bearing a simplified farnesyl side chain. The evaluation of these key analogues, along with those derived from their further functionalizations, permitted a scan of the key structural features providing new insights into the role of the substituents found in both the pyridyl core as well as the side chain. A strategic late stage heterobenzylic Stille cross-coupling reaction of the pyridyl core with the fully elaborated side chain permitted ready access to the analogues in which each half of the molecule could be systematically and divergently modified. The pyridyl cores were assembled enlisting inverse electron demand Diels-Alder reactions of N-sulfonyl-1-azabutadienes, while key elements of side chain syntheses include an anti selective asymmetric aldol to install the C9 and C10 relative and absolute stereochemistry (for natural and ent-1) and a modified Julia olefination for formation of the C5-C6 trans double bond with convergent assemblage of the side chains.