IKARUGAMYCIN

Base Information

• Chemical Name: IKARUGAMYCIN
• CAS No.: 36531-78-9
• Molecular Formula: C₂₉H₃₈N₂O₄
• Molecular Weight: 478.632
• Hs Code.: 29419000
• Mol file: 36531-78-9.mol

Synonyms:14,17-Metheno-17H-as-indaceno[3,2-k][1,6]diazacycloheptadecine, ikarugamycinderiv.;14,17-Metheno-17H-as-indaceno[3,2-k][1,6]diazacycloheptadecine-9,16,18(1H)-trione,3-ethyl-2,3,3a,5a,5b,6,10,11,12,13,14,15,20a,21,21a,21b-hexadecahydro-22-hydroxy-2-methyl-,[2R-(2R*,3R*,3aS*,5aR*,5bS*,14S*,20aS*,21aR*,21bR*)]-;[2R-(2R*,3R*,3aS*,5aR*,5bS*,14S*,20aS*,21aR*,21bR*)]-3-Ethyl-2,3,3a,5a,5b,6,10,11,12,13,14,15,20a,21,21a,21b-hexadecahydro-22-hydroxy-2-methyl-14,17-metheno-17H-as-indaceno[3,2-k][1,6]diazacycloheptadecine-9,16,18(1H)-trione;(7E,19E)-3-ethyl-16-hydroxy-2-methyl-2,3,3a,5a,5b,6,10,11,12,13,14,15,20a,21,21a,21b-hexadecahydro-1H-14,17-methano-as-indaceno[3,2-k][1,6]diazacycloheptadecine-9,18,22-trione;

Chemical Property of IKARUGAMYCIN

Chemical Property:

• Vapor Pressure: 2.41E-23mmHg at 25°C
• Refractive Index: 1.603
• Boiling Point: 710.8 °C at 760 mmHg
• Flash Point: 383.7 °C
• PSA: 95.50000
• Density: 1.22 g/cm³
• LogP: 4.67280
• Storage Temp.: ?20°C
• Solubility.: chloroform: soluble1mg/mL (requires heating and sonication)

Purity/Quality:

98%,99%, ^*data from raw suppliers

Ikarugamycin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 25
• Safety Statements: 45

MSDS Files:

SDS file from LookChem

Useful:

• Description: Ikarugamycin is a macrocyclic antibiotic first isolated from Streptomyces sp. that demonstrates potent antiprotozoal activity. It exhibits cytotoxic effects in cancer cell lines, inhibiting cell proliferation (IC50 = 221.3 nM in HL-60 cells) through genotoxicity and by inducing apoptosis and activation of caspases. It also was shown to significantly inhibit oxidized low-density lipoprotein-induced accumulation of cholesteryl esters in macrophages at 1-4 μM. Additionally, ikarugamycin is used to inhibit clathrin-coated pit-mediated endocytosis.
• Uses: Ikarugamycin is an unusual pentacyclic tetramic acid produced by Streptomyces phaeochromogenes, with potent activity against the protozoan, Trichomonas vaginalis, reported in 1972. Ikarugamycin also demonstrates selective Gram positive antibacterial activity, and anti-ucler activity possibly via inhibition of H. pylori. In addition, ikarugamycin inhibits the uptake of oxidized low-density lipoprotein in mouse macrophages, blocks PMA and Nef-mediated cell surface CD4 down-regulation, and inhibits clathrin-coated pit-mediated endocytosis. Importantly, ikarugamycin is emerging as a useful agent for studying the process of endocytosis. Ikarugamycin has been used as an inhibitor of clathrin coated pit-mediated endocytosis in flow cytometry, as CME inhibitor to determine its suitability as a tool to study and distinguish endocytic pathways in mammalian cells and for endocytic inhibitor treatment in Hela cells.

Technology Process of IKARUGAMYCIN

There total 16 articles about IKARUGAMYCIN which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 20.0%

C38H48N2O6 (131213-24-6) → (+)-ikarugamycin (36531-78-9,91869-42-0)

Guidance literature:

With trifluoroacetic acid; at 62 ℃; for 0.166667h;

DOI:10.1021/ja00181a035

Reference yield:

[(2R,3R,3aS,5R,5aS,6R,7R,8aR,8bS)-5-(tert-Butyl-dimethyl-silanyloxy)-2-dimethoxymethyl-6-ethyl-7-methyl-dodecahydro-as-indacen-3-yl]-acetaldehyde (131196-56-0) → (+)-ikarugamycin (36531-78-9,91869-42-0)

Guidance literature:

Multi-step reaction with 14 steps

1: 1.) triphenylphosphine / 1.) CH₂Cl₂, 0 deg C, 15 min, 2.) 15 min

2: 1.) n-butyllithium / 1.) THF, hexane, from -78 deg C to 25 deg C, 55 min, 2.) from -78 deg C to to 10 deg C, 100 min

3: K₂CO₃ / H₂O; methanol / 4 h / 43 °C

4: tetrahydrofuran / 0.83 h / 25 °C

5: 86 mg / 4-(dimethylamino)pyridine (DMAP) / tetrahydrofuran / 16 h

6: 92 percent / acetone, p-toluenesulfonic acid / 3 h / 25 °C

7: 1.) potassium hexamethyldisilazide / 1.) THF, toluene, a) -78 deg C, 5 min, 0 deg C, 20 min, 2.) a) 0 deg C, 30 min, b) from 0 deg C to 25 deg C, 8 h

8: 71 percent Turnov_. / acetic acid, tetrakis(triphenylphosphine)palladium⁽⁰⁾, triphenylphosphine / tetrahydrofuran / 4 h / 25 °C

9: 94 percent / toluene / 2.5 h / Heating

10: 79 percent / 1.) H₂, 2.) quinoline / 5percent Pd/BaSO₄ / ethyl acetate / 25 °C / 1.) 4 min, 2.) 5 h

11: 85 percent / 48percent hydrofluoric acid / acetonitrile / 0.22 h / 25 °C

12: 36 percent Turnov_. / CH₃OC(O)NSO₂NEt₃ (Burgess reagent) / benzene / 25 - 50 °C

13: 66 percent / t-BuOK / 2-methyl-propan-2-ol / 0.17 h / 25 °C

14: 20 percent / trifluoroacetic acid / 0.17 h / 62 °C

With quinoline; dmap; tetrakis(triphenylphosphine) palladium⁽⁰⁾; n-butyllithium; Burgess Reagent; hydrogen fluoride; potassium tert-butylate; hydrogen; potassium hexamethylsilazane; potassium carbonate; toluene-4-sulfonic acid; acetic acid; triphenylphosphine; acetone; trifluoroacetic acid; Pd-BaSO₄; In tetrahydrofuran; methanol; water; ethyl acetate; toluene; acetonitrile; tert-butyl alcohol; benzene;

DOI:10.1021/ja00181a035

Reference yield:

tert-Butyl-[(2R,3R,3aS,4R,5aS,6R,7R,8aS,8bR)-6-(3,3-dibromo-allyl)-7-dimethoxymethyl-3-ethyl-2-methyl-dodecahydro-as-indacen-4-yloxy]-dimethyl-silane (131196-57-1) → (+)-ikarugamycin (36531-78-9,91869-42-0)

Guidance literature:

Multi-step reaction with 13 steps

1: 1.) n-butyllithium / 1.) THF, hexane, from -78 deg C to 25 deg C, 55 min, 2.) from -78 deg C to to 10 deg C, 100 min

2: K₂CO₃ / H₂O; methanol / 4 h / 43 °C

3: tetrahydrofuran / 0.83 h / 25 °C

4: 86 mg / 4-(dimethylamino)pyridine (DMAP) / tetrahydrofuran / 16 h

5: 92 percent / acetone, p-toluenesulfonic acid / 3 h / 25 °C

6: 1.) potassium hexamethyldisilazide / 1.) THF, toluene, a) -78 deg C, 5 min, 0 deg C, 20 min, 2.) a) 0 deg C, 30 min, b) from 0 deg C to 25 deg C, 8 h

7: 71 percent Turnov_. / acetic acid, tetrakis(triphenylphosphine)palladium⁽⁰⁾, triphenylphosphine / tetrahydrofuran / 4 h / 25 °C

8: 94 percent / toluene / 2.5 h / Heating

9: 79 percent / 1.) H₂, 2.) quinoline / 5percent Pd/BaSO₄ / ethyl acetate / 25 °C / 1.) 4 min, 2.) 5 h

10: 85 percent / 48percent hydrofluoric acid / acetonitrile / 0.22 h / 25 °C

11: 36 percent Turnov_. / CH₃OC(O)NSO₂NEt₃ (Burgess reagent) / benzene / 25 - 50 °C

12: 66 percent / t-BuOK / 2-methyl-propan-2-ol / 0.17 h / 25 °C

13: 20 percent / trifluoroacetic acid / 0.17 h / 62 °C

With quinoline; dmap; tetrakis(triphenylphosphine) palladium⁽⁰⁾; n-butyllithium; Burgess Reagent; hydrogen fluoride; potassium tert-butylate; hydrogen; potassium hexamethylsilazane; potassium carbonate; toluene-4-sulfonic acid; acetic acid; triphenylphosphine; acetone; trifluoroacetic acid; Pd-BaSO₄; In tetrahydrofuran; methanol; water; ethyl acetate; toluene; acetonitrile; tert-butyl alcohol; benzene;

DOI:10.1021/ja00181a035

upstream raw materials:

C₃₈H₄₈N₂O₆

[(2R,3R,3aS,5R,5aS,6R,7R,8aR,8bS)-5-(tert-Butyl-dimethyl-silanyloxy)-2-dimethoxymethyl-6-ethyl-7-methyl-dodecahydro-as-indacen-3-yl]-acetaldehyde

tert-Butyl-[(2R,3R,3aS,4R,5aS,6R,7R,8aS,8bR)-6-(3,3-dibromo-allyl)-7-dimethoxymethyl-3-ethyl-2-methyl-dodecahydro-as-indacen-4-yloxy]-dimethyl-silane

methyl (2R,3R,3aS,5R,5aS,6R,7R,8aR,8bS)-5-(tert-butyldimethylsiloxy)-6-ethyl-2-formyldodecahydro-7-methyl-as-indacene-3-tetrolate 2-(dimethyl acetal)

Refernces