104987-12-4

Basic information

• Product Name: Ascomycin
• Synonyms: AAG;FK-520;FR-900520;IMMUNOMYCIN;ASCOMYCIN, STREPTOMYCES HYGROSCOPICUS;ASCOMYCIN, STREPTOMYCES HYGROSCOPICUS VAR ASCOMYCETICUS;12,18-tetramethyl-,(3s-(3r*(e(1s*,3s*,4s*)),4s*,19s*,26ar*))--10;8-ethyl-3-(2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl)-14,16-dimethoxy
• CAS NO: 104987-12-4
• Molecular Formula: C₄₃H₆₉NO₁₂
• Molecular Weight: 792.01
• EINECS: 200-835-2
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Macrolactams;Antibiotics;Antibiotics A to;Antibiotics A-FAntibiotics;Antibiotics by Application;AntifungalAntibiotics;Antineoplastic and Immunosuppressive AntibioticsAntibiotics;Chemical Structure Class;Inhibits an EnzymeAntibiotics;Mechanism of Action;Spectrum of Activity;antibiotic;Inhibitors
• Mol File: 104987-12-4.mol

Chemical Properties

• Melting Point: 153-157°C
• Boiling Point: 868℃
• Flash Point: >110°(230°F)
• Appearance: White solid
• Density: 1.19 g/cm³
• Refractive Index: 1.543
• Storage Temp.: −20°C
• Solubility: ≥38.9 mg/mL in DMSO; insoluble in H2O; ≥98.6 mg/mL in EtOH
• PKA: 9.97±0.70(Predicted)
• Water Solubility: Soluble in DMSO at 65mg/ml; soluble in ethanol at 50mg/m; with warming. Very poorly soluble in water
• CAS DataBase Reference: Ascomycin(CAS DataBase Reference)
• NIST Chemistry Reference: Ascomycin(104987-12-4)
• EPA Substance Registry System: Ascomycin(104987-12-4)

Safety Data

• Hazard Codes: Xn,F
• Statements: 20/21/22-36-11
• Safety Statements: 36/37-16
• RIDADR: UN 1648 3 / PGII
• WGK Germany: 3
• RTECS: KD4185000
• F: 10
• Hazardous Substances Data: 104987-12-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Ascomycin is used as an immunosuppressant for preventing organ transplant rejection and treating autoimmune diseases. Its immunosuppressive properties make it a valuable compound in the development of drugs for various medical conditions.
Used in Antifungal Applications:
Ascomycin exhibits limited but potent antifungal activity, making it useful in the development of antifungal medications to combat fungal infections.
Used in Research and Development:
Everolimus, a semi-synthetic macrocyclic lactone prepared from Ascomycin, has greater stability and bioavailability. It is extensively cited in the literature with over 2,000 citations, indicating its importance in research and development for various therapeutic applications, particularly in the field of oncology.
Used in Drug Delivery Systems:
Ascomycin and its derivatives, such as everolimus, can be incorporated into drug delivery systems to improve their efficacy and bioavailability. This can involve the use of organic and metallic nanoparticles as carriers for targeted delivery to specific cells or tissues, enhancing the therapeutic outcomes of the compounds.

Biological Activity

ascomycin (fk 520, fr900520) is a novel neutral macrolide immunosuppressant, isolated from the cultured broth of streptomyces hygroscopicus subsp. yakushimaensis no. 7238.

in vitro

ascomycin (fk 520, fr900520) suppressed lymphocyte reaction in a dose dependent fashion. ascomycin was non-toxic at concentrations less than 3,200 nm, at which the percent inhibition was 18.9%. ascomycin showed antifungal activity against aspergillus fumigatus ifo 5840. ascomycin had no inhibitory effect on bacteria or yeast at 100 μg/ml [1].

in vivo

ascomycin was dose-dependently effective and clearly prolonged skin allograft survival at 3.2 mg/kg or more, though all skin allografts were rejected within 7 days in rats treated intramuscularly with olive oil. ascomycin, dissolved in olive oil, showed no adverse effect when administered intraperitoneally to ddy mice (male, 8 weeks old) at 100 mg/kg [1].

references

[1] hatanaka h, kino t, miyata s, inamura n, kuroda a, goto t, tanaka h, okuhara m. fr-900520 and fr-900523, novel immunosuppressants isolated from a streptomyces. ii. fermentation, isolation and physico-chemical and biological characteristics. j antibiot (tokyo). 1988;41(11):1592-601.

InChI:InChI=1/C43H67NO12/c1-10-30-18-24(2)17-25(3)19-36(53-8)39-37(54-9)21-27(5)43(51,56-39)40(48)41(49)44-16-12-11-13-31(44)42(50)55-38(28(6)33(46)23-34(30)47)26(4)20-29-14-15-32(45)35(22-29)52-7/h18,20,25,27-32,35-39,45,51H,10-17,19,21-23H2,1-9H3/b24-18-,26-20+/t25-,27-,28-,29+,30-,31+,32-,35-,36+,37+,38-,39-,43-/m1/s1

Upstream product

• 668990-41-8 C₆₁H₁₁₃NO₁₃Si₃ 
• 668990-40-7 C₆₁H₁₁₁NO₁₂Si₃ 
• 668990-42-9 C₆₁H₁₁₃NO₁₂Si₃ 
• 273752-75-3 2(R),10(S),11(S)-cyclo-ascomycin 
• 671222-63-2 11-epi-ascomycin 
• 137071-45-5 24,33-bis-OTBDMS-ascomycin 

Downstream Products

• 143839-74-1 L 685818 
• 134226-79-2 33-(tert-butyldimethylsilyl)-24-deoxy-ascomycin 
• 148146-94-5 C₅₂H₇₇NO₁₄ 
• 233600-08-3 ascomycin hydrazone 
• 261759-01-7 17-but-1-enyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxy-cyclohexyl)-1-methyl-vinyl]-21,23-dimethoxy-13,17,19,25-tetramethyl-11,26-dioxa-4-aza-tricyclo[20.3.1.0^4,9]hexacosane-2,3,10,16-tetraone 
• 261759-00-6 4-β-methoxy-9-dihydroascomycin 

Relevant articles and documents

METHOD OF PURIFYING MACROLIDES

A method for purifying macrolide is provided in which a loading charge of macrolide is placed in juxtaposition with a bed of wet sorption resin, the loading charge and bed are eluted at a temperature greater than 30°C with an eluent of an organic solvent selected from the group consisting of THF, acetonitrile, n-propyl alcohol, iso-propyl alcohol, ethyl alcohol, and acetone, the heart cut of the eluent is collected, and purified macrolide is collected.

METHOD OF PURIFYING MACROLIDES

Provided is a method of purifying a macrolide, especially tacrolimus, that includes loading macrolide onto a bed of sorption resin and elting with a suitable eluent such as a combination of water and tetrahydrofuran.

A PROCESS FOR THE RECOVERY OF SUBSTANTIALLY PURE TRICYCLIC MACROLIDE

Process for the recovery of a macrolide in substantially pure form comprising: a) treating the macrolide with water immiscible solvent followed by concentration, b) mixing with water, water miscible solvent or mixture thereof, c) performing hydrophobic interaction chromatography and collecting the fractions, d)extracting the fraction containing macrolide with water immiscible solvent followed by concentration, e) adding water miscible solvent to effect separation of impurities from the macrolide compound, f) performing silica gel chromatography and collecting the fractions, g) isolating the macrolide compound in substantially pure form. The macrolide is preferably rapamycin, tacrolimus or immunomycin.

CRYSTALLIZATION AND PURIFICATION OF MACROLIDES

Provided is a method for crystallization and purification of a macrolide such as tacrolimus, sirolimus, pimecrolimus, or everolimus that includes the step of providing a combination of a macrolide, and a polar solvent, dopolar aprotic solvent, or hydrocarbon solvent at pH of 7 or above.

Selective transformation of ascomycin into 11-epi-ascomycin

Within the binding domain, ascomycin features the unusual pattern of a masked tricarbonyl moiety, which potentially allows for high structural diversity via simple isomerisation events. A cascade of diastereoselective rearrangement reactions at the binding domain, allowing the conversion of ascomycin into 11-epi-ascomycin is herein reported.

Regio- and stereoselective preparation of ascomycin-d1 and FK 506-d1

The immunosuppressive macrolides ascomycin 1 and FK 506 2 were stereoselectively deuteriated at C(32) using Curran's radical translocating method. Both AIBN and Et3B/O2 were tested as radical initiator for the radical translocation/reduction step with Bu3SnD as reducing agent. Despite only minor structural differences, ascomycin and FK 506 showed remarkably different behaviour under the radical translocation/reduction conditions. Higher stereoselectivities were observed with Et3B/O2 as initiator, presumably due to lower reaction temperatures applied in this case. Copyright