2738-64-9

Usage

Uses

1. Used in Pharmaceutical Industry:
Piericidin A is used as an antibiotic for its potent inhibitory action on NADH-ubiquinone oxidoreductase (Complex I) in both mitochondrial and bacterial systems. This property makes it a valuable compound in the development of new antibiotics and understanding the mechanisms of action for various pathogens.
2. Used in Research and Development:
Piericidin A is used as a specific, potent inhibitor of Complex I for studying the role of this enzyme in mitochondrial function. It is an essential tool in both normal and pathophysiological research, aiding in the understanding of complex I's involvement in various biological processes and potential therapeutic targets.
3. Used in Drug Resistance Studies:
Piericidin A is used to induce cell death in glucose-deprived, etoposide-resistant HT-29 cells, with an IC50 of 7.7 nM. This application helps researchers investigate the mechanisms of drug resistance and develop strategies to overcome resistance in cancer treatment.
4. Used in Drug Delivery Systems:
Although not explicitly mentioned in the provided materials, Piericidin A could potentially be used in drug delivery systems to improve its bioavailability and targeting efficiency. This application would require further research and development to optimize the delivery method and ensure the compound's effectiveness in various therapeutic applications.

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

• 871316-12-0 (5,6-dimethoxy-3-methyl-pyridin-2-yl)-methanol 
• 912877-17-9 2-[(Z)-Hydroxyimino]-3-methyl-but-3-enoic acid ethyl ester 
• 912877-27-1 2-[(2E,5E,7E,11E)-(9S,10S)-10-(tert-Butyl-dimethyl-silanyloxy)-3,7,9,11-tetramethyl-trideca-2,5,7,11-tetraenyl]-5,6-dimethoxy-3-methyl-pyridin-4-ol 
• 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 

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 academic research and scientific papers

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.

Polyketides and Anthranilic Acid Possessing 6-Deoxy-α- l -talopyranose from a Streptomyces Species

A bioassay-guided investigation in conjunction with chemical screening led to the isolation of three new glycosides, ulleungoside (1), 2-methylaminobenzoyl 6-deoxy-α-l-talopyranoside (2), and naphthomycinoside (3), along with three known secondary metabolites (5-7) from Streptomyces sp. KCB13F030. Their structures were elucidated by detailed NMR and MS spectroscopic analyses. Absolute configurational analysis of the sugar units based on the magnitudes of the coupling constants, NOESY correlations, chemical derivatization, and optical rotation measurements revealed that compounds 1-3 and 5 incorporate the rare deoxyhexose 6-deoxy-α-l-talopyranose. The absolute configuration of a polyketide extender unit of 3 was determined by applying the J-based configuration analysis and modified Mosher's method. Ulleungoside (1) and naphthomycin A (7) showed in vitro inhibitory effects against indoleamine 2,3-dioxygenase activity. Further bioevaluation revealed that compounds 1 and 7 had moderate antiproliferative activities against several cancer cell lines, and compounds 5 and 6, which are members of the piericidin family, induced autophagosome accumulation.

Total synthesis of (+)-piericidin A1 and (-)-piericidin B1

The convergent syntheses of (+)-piericidin A1 1 and (-)-piericidin B1 2 have been achieved based on classical Julia-Lythgoe olefination between 4-hydroxy-5,6-dimethoxy-3-methyl-2-[5-oxo-3-methyl-pent-(2E)-enyl]-pyridine 3 correspondi

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.

Total synthesis of piericidin A1 and B1

The first total syntheses of piericidin A1 and B1 are disclosed and unambiguously establish the relative and absolute stereochemistry of the natural products by an approach that will facilitate the synthesis of a series of analogues. Central to the approach is an inverse electron demand Diels-Alder reaction of a N-sulfonyl-1-aza-1,3-butadiene with tetramethoxyethene followed by Lewis acid-promoted aromatization used to assemble the functionalized pyridine core. Additional key elements in the convergent approach include the use of an anti-aldol reaction to install the C9 and C10 relative and absolute stereochemistry, a modified Julia olefination for formation of the C5-C6 trans double bond with convergent assemblage of the side chain, and a penultimate heterobenzylic Stille cross-coupling reaction of the pyridyl core with the fully elaborated side chain. Copyright