6833-84-7

Usage

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 
• 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 
• 159247-96-8 C₄₀H₆₆O₁₃ 
• 215110-67-1 Toluene-4-sulfonic acid (3S,4R,7R)-7-[(R)-2-(tert-butyl-dimethyl-silanyloxy)-propyl]-3-methyl-2-oxo-oxepan-4-yl ester 
• 215110-65-9 (3S,4R,7R)-7-[(R)-2-(tert-Butyl-dimethyl-silanyloxy)-propyl]-4-hydroxy-3-methyl-oxepan-2-one 
• 215110-58-0 (3R,6R)-3-(Dimethyl-p-tolyl-silanyl)-6-hydroxy-8-oxo-nonanoic acid 
• 215110-77-3 (S)-2-{(2S,5R)-5-[(R)-2-(tert-Butyl-dimethyl-silanyloxy)-propyl]-tetrahydro-furan-2-yl}-propionic acid methyl ester 
• 159276-76-3 (3R,4R,7R)-7-[(R)-2-(tert-Butyl-dimethyl-silanyloxy)-propyl]-4-(dimethyl-p-tolyl-silanyl)-3-methyl-oxepan-2-one 
• 159276-77-4 (3R,6R,8R)-3-(Dimethyl-p-tolyl-silanyl)-6,8-dihydroxy-nonanoic 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 academic research and scientific papers

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.

Stereocontrol in organic synthesis using silicon-containing compounds. A synthesis of nonactin

The enantiomeric purity of (1R)-1-(1′-naphthyl)ethanol 7 was raised by Korean's method by separating its oxalate 11 from its diastereoisomer by crystallisation. The alcohol 7 was used to open the anhydride of (3RS,4SR)-3,4-bis[dimethyl(4-methylphenyl)silyl]hexane-1,6-dioic acid with selectivity of 96:4 for one of the enantiotopic carbonyl groups, allowing the synthesis of (3R,4S)-3,4-bis[dimethyl(4-methylphenyl)silyl]hexane-1,6-dioic acid 6-(2-trimethylsilylethyl) ester 10. This acid was converted into the allylsilane methyl (E)-(3S,4R)-3,4-bis[dimethyl(4-methylphenyl)silyl]-7-(2-methyldioxolan-2-yl) hept-5-enoate 15, the carboxylic acid derived from which underwent epoxidation with unexpected silyl migration to give (35,4S,5S,6R)-3,5-bis[dimethyl(4-methylphenyl)silyl]-6-hydroxy-7-(2- methyldioxolan-2-yl)heptano-4-lactone 17. Desilylative elimination and hydrogenation then gave the alcohol (3R,6R)-3-[dimethyl(4-methylphenyl)silyl]-6-hydroxy-7-(2-methyldioxolan-2-yl) heptanoic acid 19, in which the relative and absolute configuration at C-3 and C-6 have been controlled. The relative configuration at C-8 was controlled by anti-selective reduction of a 6-hydroxy-8-ketone using Evans' method, and at C-2 by anti-selective enolate methylation of the β-silyl lactone 20. Silyl-to-hydroxy conversion with retention at C-3 and displacement of the tosylate with inversion at the same centre gave the correct relative and absolute configuration, completing a synthesis of methyl (+)-nonactate 4. The relative configuration at C-8 was controlled in the opposite sense by syn-selective reduction of a 6-hydroxy-8-ketone using Prasad's conditions, and at C-2 in the opposite sense by anti-selective enolate methylation of the open-chain β-silyl ester 22. Silyl-to-hydroxy conversion with retention at C-3 and displacement of the tosylate with inversion at C-6 gave the correct relative and absolute configuration completing a synthesis of the pseudo-enantiomer, benzyl (-)-nonactate 25. Some protecting group changes and coupling of these two fragments gave the "dimers" 28 and 29, coupling of which gave the "tetramer" 30. Ring closure of this material using Yamaguchi's method gave nonactin in 73% yield, substantially better than in any previous synthesis.

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.

Total Synthesis of Nonactin

Utilizing the efficient preparation of (-)-methyl 8-epi-nonactate (4a) and (+)-nonactic acid (2b) and high yielding macrolactonization based on the high dilution version of the Yamaguchi's method, the total synthesis of nonactin has been accomplished.

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.

Biosynthesis of the Macrotetrolide Antibiotics; The Incorporation of Carbon-13 and Oxygen-18 Labelled Acetate, Propionate, and Succinate

The biosynthesis of the macrotetrolide antibiotics, in particular nonactin, has been studied using carbon-13 and oxygen-18 enriched acetate and propionate, as well as carbon-13 enriched succinate, in feeding experiments with the producing organism Streptomyces griseus.A protocol is described which allows the separation of derivatives formed from each enantiomer of nonactic and homononactic acids.From a study of the incorporation of the labelled precursors into these derivatives it could be shown that the origins of the carbon and oxygen atoms in each enantiomer are identical.The carbon backbone of nonactic acid is assembled from two acetate, one succinate, and one propionate units, and the C-O bonds at C-8, C-6, and C-1 are derived intact from the primary precursors.Based on these data a new proposal is made to account for the biosynthesis of (+/-)-nonactate, and nonactin, in S. griseus.