6833-84-7

Basic information

• Product Name: NONACTIN
• Synonyms: ta-25-m-i;NONACTIN;NONACTIN, STREPTOMYCES GRISEUS;POLYNACTIN;NONACTIN FROM STREPTOMYCES GRISEUS;NONACTINE, FROM STREPTOMYCES SP.;NONACTIN FROM STREPTOMYCES TSUSIMAENSIS;nonactinfromstreptomycessp.
• CAS NO: 6833-84-7
• Molecular Formula: C₄₀H₆₄O₁₂
• Molecular Weight: 736.93
• EINECS: 229-911-3
• Product Categories: inhibitor
• Mol File: 6833-84-7.mol
• Article Data: 7

Chemical Properties

• Melting Point: 147-148°
• Boiling Point: 890.6 °C at 760 mmHg
• Flash Point: 352.7 °C
• Appearance: white to faint yellow/
• Density: 1.041 g/cm³
• Refractive Index: 1.452
• Storage Temp.: 2-8°C
• Solubility: chloroform: soluble10mg/mL
• Sensitive: Moisture Sensitive
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 2 months.
• Merck: 13,6709
• BRN: 76434
• CAS DataBase Reference: NONACTIN(CAS DataBase Reference)
• NIST Chemistry Reference: NONACTIN(6833-84-7)
• EPA Substance Registry System: NONACTIN(6833-84-7)

Safety Data

• Hazard Codes: Xi
• Safety Statements: 22-24/25
• WGK Germany: 3
• RTECS: RH1685000
• F: 10-21
• Hazardous Substances Data: 6833-84-7(Hazardous Substances Data)

Usage

Description

NONACTIN is a monovalent cation ionophore with high selectivity for NH4+ and K+. It is the smallest member of the macrotetrolide complex produced by a range of Streptomyces species. Originally, the name "nonactin" reflected the lack of biological activity, but it has since been found to upregulate levels of mitochondrial stress proteins HSP58 and GRP75 and abolish mitochondrial membrane potential.

Uses

Used in Pharmaceutical Industry:
NONACTIN is used as an ionophore antibiotic for selectively binding K+ and NH4+. Its high selectivity for these ions makes it a valuable tool in the development of pharmaceuticals and drug delivery systems.
Used in Research Applications:
NONACTIN is used as a research tool for studying the effects of monovalent cation ionophores on mitochondrial function and stress protein levels. Its ability to abolish mitochondrial membrane potential and upregulate stress proteins makes it a useful compound for investigating cellular responses to various stimuli.
Used in Veterinary Medicine:
NONACTIN may be used in veterinary medicine as an ionophore antibiotic to selectively bind K+ and NH4+ in animals, helping to maintain proper ion balance and support overall health.

Biological Activity

Monovalent cation ionophore that displays selectivity for K + and NH 4 + (K + = NH 4 + > Na + > Mg 2+ > Li + >> Ca 2+ for nonactin-EVA sensor). Induces cation transport across artificial membranes. Also inhibits P-glycoprotein-mediated efflux of chemotherapeutic agents in multiple-drug resistant cancer cells. Antibiotic.

Purification Methods

This macrotetrolide antibiotic crystallises from MeOH as colourless needles and is dried at 90o/20hours/high vacuum. [Cordaz et al. Helv Chim Acta 38 1445 1955, crystal structure: Dobler Helv Chim Acta 55 1371 1972, Gambos et al. Tetrahedron Lett 3391 1975, Beilstein 19/12 V 751.]

References

1) Garcia et al. (2003), Determination of potassium ions in pharmaceutical samples by FIA using a potentiometric electrode based on ionophore nonactin occulded in EVA membrane; J. Pham. Biomed. Anal., 31 11 2) Mizzen et al. (1989), Identification, characterization and purification of two mammalian stress proteins present in mitochondria, grp 75, a member of the hsp 70 family and hsp 58, a homolog of the bacterial groEL protein; J. Biol. Chem., 264 20664 3) Dudani et al. (1990), Effects of antimitotic and antimitochondrial agents on the cellular distribution of microtubules and mitochondria; Cytobios, 63 95

InChI:InChI=1/C40H64O12/c1-21-17-29-9-13-34(49-29)26(6)38(42)46-23(3)19-31-11-15-36(51-31)28(8)40(44)48-24(4)20-32-12-16-35(52-32)27(7)39(43)47-22(2)18-30-10-14-33(50-30)25(5)37(41)45-21/h21-36H,9-20H2,1-8H3/t21-,22+,23+,24-,25-,26-,27-,28?,29+,30-,31-,32+,33+,34-,35-,36+/m1/s1

Upstream product

• 83587-77-3 sodium <1-(18)O2, 1-(13)C>propionate 
• 91177-79-6 (+)-nonactyl-(-)-nonactic acid 
• 159247-96-8 C₄₀H₆₆O₁₃ 
• 900807-28-5 3-((4R,6R)-2,2,6-Trimethyl-[1,3]dioxan-4-yl)-propionaldehyde 
• 900807-27-4 3-((4R,6R)-2,2,6-Trimethyl-[1,3]dioxan-4-yl)-propan-1-ol 
• 900807-24-1 1-(tert-butyl-dimethyl-silanyloxy)-6-hydroxy-heptan-4-one 
• 900807-25-2 (2R,4R)-7-(tert-Butyl-dimethyl-silanyloxy)-heptane-2,4-diol 
• 900807-26-3 tert-Butyl-dimethyl-[3-((4R,6R)-2,2,6-trimethyl-[1,3]dioxan-4-yl)-propoxy]-silane 
• 900807-23-0 1-{2-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-[1,3]dithian-2-yl}-propan-2-ol 
• 900807-31-0 (S)-3-{(S)-2-[(2S,5R)-5-((R)-2-Hydroxy-propyl)-tetrahydro-furan-2-yl]-propionyl}-4-phenyl-oxazolidin-2-one 
• 900807-29-6 (S)-3-[(2S,3R)-3-Hydroxy-2-methyl-5-((4R,6R)-2,2,6-trimethyl-[1,3]dioxan-4-yl)-pentanoyl]-4-phenyl-oxazolidin-2-one 
• 900807-30-9 Methanesulfonic acid (1R,4R,6R)-4,6-dihydroxy-1-[(S)-1-methyl-2-oxo-2-((S)-2-oxo-4-phenyl-oxazolidin-3-yl)-ethyl]-heptyl ester 
• 16221-10-6 (+)-(2S,3S,6R,8R)-epi-Nonactic acid 
• 159153-48-7 (S)-2-((2S,5R)-5-((R)-2-(tert-butyldimethylsiloxy)propyl)tetrahydrofuran-2-yl)propanoic acid 

Downstream Products

• 128806-56-4 Toluene-4-sulfonic acid (S)-2-[(2R,5S)-5-(2-oxo-propyl)-tetrahydro-furan-2-yl]-propyl ester 

Relevant articles and documents

Synthesis of nonactin and the proposed structure of trilactone

An efficient enantioselective route to nonactin using a novel β-inversion of an Evans syn aldol to construct the THF ring is presented. Through total synthesis, the structure for trilactone proposed in the literature is shown likely to be incorrect.

Total synthesis of nonactin

Utilizing the efficient preparation of (+)-nonactic acid (2a) and (-)-methyl-8-epi-nonactate (4b) starting from optically active 2-isoxazolines 5a and 5b, respectively, the total synthesis of nonactin has been accomplished. Based on the high dilution version of the Yamaguchi's method, the final macrolactonization has been completed in high yield.

A total synthesis of nonactin

With appropriate protecting group manipulation, the nonactate esters 1 and 3, one from each enantiomeric series, are joined together in an alternating sequence to give the hydroxyacid 7, which is lactonised to give nonactin 8 in 59% overall yield.