Leptomycin B

Base Information

• Chemical Name: Leptomycin B
• CAS No.: 87081-35-4
• Molecular Formula: C₃₃H₄₈O₆
• Molecular Weight: 540.741
• Hs Code.: 29419090
• European Community (EC) Number: 617-954-4
• UNII: Y031I2N1EO
• Wikipedia: Leptomycin
• Wikidata: Q6528191
• Pharos Ligand ID: V7YYX6FVFUZR
• Metabolomics Workbench ID: 58318
• ChEMBL ID: CHEMBL486133
• Mol file: 87081-35-4.mol

Synonyms:2,10,12,16,18-nonadecapentaenoic acid, 19-(3,6-dihydro-3-methyl-6-oxo-2H-pyran-2-yl)-17-ethyl-6-hydroxy-3,5,7,9,11,15-hexamethyl-8-oxo-;CI 940;CI-940;elactocin;leptomycin B;PD 114720;PD-114,720

Chemical Property of Leptomycin B

Chemical Property:

• Appearance/Colour: White crystalline solid.
• Vapor Pressure: 2.53E-24mmHg at 25°C
• Melting Point: 41-44 ºC
• Boiling Point: 725.8 °C at 760 mmHg
• Flash Point: 224.7 °C
• PSA: 100.90000
• Density: 1.072 g/cm³
• LogP: 6.78470
• Storage Temp.: −20°C
• Solubility.: Supplied in solution in ethanol (1 mg/ml). Further dilutions may be made with either ethanol or DMSO.
• XLogP3: 7.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 15
• Exact Mass: 540.34508925
• Heavy Atom Count: 39
• Complexity: 1020

Purity/Quality:

96% 1H NMR ^*data from raw suppliers

LeptomycinB ^*data from reagent suppliers

Safty Information:

• Pictogram(s): TF
• Hazard Codes: F,T
• Statements: 23/25-36/38-39/23/24/25-23/24/25-11
• Safety Statements: 7-16-24-33-45-36/37

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CCC(=CC(C)CC=CC(=CC(C)C(=O)C(C)C(C(C)CC(=CC(=O)O)C)O)C)C=CC1C(C=CC(=O)O1)C
• Isomeric SMILES: CC/C(=C/[C@H](C)C/C=C/C(=C/[C@@H](C)C(=O)[C@@H](C)[C@@H]([C@@H](C)C/C(=C/C(=O)O)/C)O)/C)/C=C/[C@H]1[C@H](C=CC(=O)O1)C
• Description: Leptomycin B (87081-35-4) is an inhibitor of nuclear export of proteins. Acts via covalent binding to and inhibiting CRM1/exportin-1.1 Inhibits the nuclear export of the HIV regulatory protein Rev.2 Leptomycin B stabilizes p53 by blocking its nuclear export.3
• Uses: Leptomycin B is the dominant and most studied member of the leptomycin class, isolated from selected Streptomyces strains. Leptomycin B is a nanomolar active and specific nuclear export inhibitor. Its target is CRM1/exportin1, a protein in the nuclear export sequence (NES). Proteins affected include c-Abl, cyclin B1, HIV-1 Rev, IκB, MPF, MAP/ERK, MDM2/p53, NF-κB/IκB7 and PKA. Leptomycin B inhibits export of many RNAs, e.g. COX-2 and c-FOS mRNA. Leptomycin B also shows antifungal and antibacterial and potent antitumour activities. Biological tool for studying nuclear localization and protein trafficking in eukaryotic cells. Potent, specific inhibitor of nuclear export signal (NES)-dependent protein export from the nucleus

Technology Process of Leptomycin B

There total 33 articles about Leptomycin B 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:

(2R,3S)-1-Benzyloxy-3-methyl-pent-4-yn-2-ol (217640-04-5) → leptomycin B (87081-35-4)

Guidance literature:

Multi-step reaction with 17 steps

1: 1.) nBuLi, iPr₂NH / 1.) THF, -78 deg C; 2.) THF, -60 deg C

2: H₂, quinoline / Pd/BaSO₄ / ethanol

3: benzene / Heating

4: DIBAL-H / CH₂Cl₂ / -78 °C

5: PPTS / benzene

6: 89 percent / lithium di-tert-butylbiphenyl / tetrahydrofuran / -78 °C

7: 1.) (COCl)2; 2.) Et₃N / 1.) DMSO, CH₂Cl₂; 2.) -78 deg C

8: 59 percent / LiCH₂S(O)CH₃ / toluene / -78 - 5 °C

9: Dowex HCR-W₂ / acetone; H₂O / 40 °C

10: Ag₂CO₃-celite / benzene / 50 °C

11: 89 percent / DDQ, CH₂Cl₂, tBuOH, buffer

12: 99 percent / Dess-Martin periodinane / CH₂Cl₂

13: 90 percent / LiCH₂S(O)CH₃ / toluene / -78 - 5 °C

14: 71 percent / Dess-Martin periodinane / CH₂Cl₂

15: 89 percent / HF*pyridine, pyridine / tetrahydrofuran

16: MnO₂ / benzene

17: NaClO₂, NaH₂PO₄, H₂O₂ / acetonitrile

With pyridine; quinoline; manganese(IV) oxide; sodium chlorite; sodium dihydrogenphosphate; n-butyllithium; oxalyl dichloride; dichloromethane; Dowex HCR-W₂; hydrogen; dihydrogen peroxide; pyridinium p-toluenesulfonate; diisobutylaluminium hydride; Lithium dimsyl; lithium 4,4′-di-tert-butylbiphenylide; Dess-Martin periodane; pyridine hydrogenfluoride; triethylamine; diisopropylamine; silver carbonate; 2,3-dicyano-5,6-dichloro-p-benzoquinone; tert-butyl alcohol; Pd-BaSO₄; In tetrahydrofuran; ethanol; dichloromethane; water; acetone; toluene; acetonitrile; benzene;

DOI:10.1016/S0040-4039(98)01809-7

Reference yield:

(4S,5R)-6-Benzyloxy-5-hydroxy-4-methyl-hex-2-ynoic acid → leptomycin B (87081-35-4)

Guidance literature:

Multi-step reaction with 16 steps

1: H₂, quinoline / Pd/BaSO₄ / ethanol

2: benzene / Heating

3: DIBAL-H / CH₂Cl₂ / -78 °C

4: PPTS / benzene

5: 89 percent / lithium di-tert-butylbiphenyl / tetrahydrofuran / -78 °C

6: 1.) (COCl)2; 2.) Et₃N / 1.) DMSO, CH₂Cl₂; 2.) -78 deg C

7: 59 percent / LiCH₂S(O)CH₃ / toluene / -78 - 5 °C

8: Dowex HCR-W₂ / acetone; H₂O / 40 °C

9: Ag₂CO₃-celite / benzene / 50 °C

10: 89 percent / DDQ, CH₂Cl₂, tBuOH, buffer

11: 99 percent / Dess-Martin periodinane / CH₂Cl₂

12: 90 percent / LiCH₂S(O)CH₃ / toluene / -78 - 5 °C

13: 71 percent / Dess-Martin periodinane / CH₂Cl₂

14: 89 percent / HF*pyridine, pyridine / tetrahydrofuran

15: MnO₂ / benzene

16: NaClO₂, NaH₂PO₄, H₂O₂ / acetonitrile

With pyridine; quinoline; manganese(IV) oxide; sodium chlorite; sodium dihydrogenphosphate; oxalyl dichloride; dichloromethane; Dowex HCR-W₂; hydrogen; dihydrogen peroxide; pyridinium p-toluenesulfonate; diisobutylaluminium hydride; Lithium dimsyl; lithium 4,4′-di-tert-butylbiphenylide; Dess-Martin periodane; pyridine hydrogenfluoride; triethylamine; silver carbonate; 2,3-dicyano-5,6-dichloro-p-benzoquinone; tert-butyl alcohol; Pd-BaSO₄; In tetrahydrofuran; ethanol; dichloromethane; water; acetone; toluene; acetonitrile; benzene;

DOI:10.1016/S0040-4039(98)01809-7

Reference yield:

(2E,10E,12E,16Z,18E)-(5S,6R,7S,9R,15R)-17-Ethyl-6-hydroxy-3,5,7,9,11,15-hexamethyl-19-((2S,3S)-3-methyl-6-oxo-3,6-dihydro-2H-pyran-2-yl)-8-oxo-nonadeca-2,10,12,16,18-pentaenal → leptomycin B (87081-35-4)

Guidance literature:

With sodium chlorite; sodium dihydrogenphosphate; dihydrogen peroxide; In acetonitrile; Yield given;

DOI:10.1016/S0040-4039(98)01809-7

upstream raw materials:

(2R,3S)-6-Isopropoxy-3-methyl-3,6-dihydro-2H-pyran-2-carbaldehyde

((2R,3S)-6-Isopropoxy-3-methyl-3,6-dihydro-2H-pyran-2-yl)-methanol

(E)-(S)-6-Methoxymethoxy-2,4-dimethyl-hex-4-enal

(5S,6R)-6-Benzyloxymethyl-5-methyl-5,6-dihydro-pyran-2-one

Refernces