Herbimycin a

Base Information

• Chemical Name: Herbimycin a
• CAS No.: 70563-58-5
• Molecular Formula: C₃₀H₄₂N₂O₉
• Molecular Weight: 574.671
• Hs Code.: 29419000
• UNII: 815WDV2HST
• Wikipedia: Herbimycin
• Wikidata: Q14200355
• NCI Thesaurus Code: C1124
• Metabolomics Workbench ID: 53215
• ChEMBL ID: CHEMBL480499
• Mol file: 70563-58-5.mol

Synonyms:geldanamycin, 17-demethoxy-15-methoxy-11-O-methyl-, (15R)-;herbimycin;herbimycin A;NSC 305978

Chemical Property of Herbimycin a

Chemical Property:

• Appearance/Colour: yellow powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 229-231 °C
• Refractive Index: 1.545
• Boiling Point: 752.4 °C at 760 mmHg
• PKA: 8.56±0.70(Predicted)
• Flash Point: 408.8 °C
• PSA: 152.48000
• Density: 1.19 g/cm³
• LogP: 3.74240
• Storage Temp.: −20°C
• Sensitive.: Light Sensitive & Hygroscopic
• Solubility.: DMSO: 7.5 mg/mL DMSO stock solution can be diluted in phosp
• XLogP3: 1.8
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 6
• Exact Mass: 574.28903092
• Heavy Atom Count: 41
• Complexity: 1150

Purity/Quality:

98%Min ^*data from raw suppliers

Herbimycin A ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 22-24/25-36-26

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CC1CC(C(C(C=C(C(C(C=CC=C(C(=O)NC2=CC(=O)C=C(C1OC)C2=O)C)OC)OC(=O)N)C)C)OC)OC
• Isomeric SMILES: C[C@H]1C[C@@H]([C@@H]([C@H](/C=C(/[C@@H]([C@H](/C=C\C=C(\C(=O)NC2=CC(=O)C=C([C@@H]1OC)C2=O)/C)OC)OC(=O)N)\C)C)OC)OC
• Description: Herbimycin A (70563-58-5) is an ansamycin antibiotic. Inhibits HSP90 and associated client proteins including v-Src, Bcr-Abl, Raf-1 and ErbB2.1,2 Herbimycin A reverts tyrosine kinase-induced oncogenic transformation without direct inhibition of phosphorylation activity.1 Inhibits angiogenesis in a rat retinopathy model.3
• Uses: Herbimycin A is the major analogue of a complex of benzoquinone ansamycin antibiotics isolated from a Streptomyces hygroscopicus. Herbimycin A inhibits the 90-kDa heat-shock protein (Hsp90) which provides essential chaperone support to various signal transduction molecules, including certain steroid hormone receptors and select kinases. Herbimycin also inhibits protein tyrosine kinase and angiogenesis. Herbimycin A is a benzoquinone ansamycin antibiotic from Streptomyces. It has herbicidal activity and acts as a cell-permeable inhibitor of non-receptor tyrosine kinases and the heat shock protein Hsp90. Herbimycin A inhibits Bcr-Abl with an IC50 value of 5 μM, a concentration that also effectively blocks Src, Yes, Fps, Ros, and ErbB but not protein kinases (PK) PKA, PKC, Rac, Myc, or Raf. Presumably through its effects on tyrosine kinase signaling, herbimycin A also impairs endothelial cell proliferation in the context of angiogenesis, NF-κB activation, phosphorylation of phospholipase C-γ1, and eggshell formation in schistosome parasites. Ansamycins, including herbimycin A and geldanamycin , bind Hsp90 and destabilize client proteins, including Src, Bcr-Abl, and ErbB2, leading to their ubiquitination and proteasomal degradation. Herbimycin A is an inhibitor of c-Abl, HSP 90, c-Src, c-Yes, Fes, and Ros. It is a COVID19-related research product.

Technology Process of Herbimycin a

There total 82 articles about Herbimycin a 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: 100.0%

carbamic acid-8,13,14,17,20,22-hexamethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-bicyclo[16.3.1]docosa-1(21),4,6,10,18(22),19-hexaen-9-yl ester (145798-89-6) → herbimycin A (70563-58-5)

Guidance literature:

With silver(II) oxide; nitric acid; In 1,4-dioxane; for 2.5h; Ambient temperature;

DOI:10.1246/bcsj.65.2974

Reference yield:

(4E,6Z,8S,9S,10E,12S,13R,14S,16S,17R)-9-hydroxy-8,13,14,17,20,22-hexamethoxy-4,10,12,16-tetramethyl-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18(22),19-hexaen-3-one (145798-98-7) → herbimycin A (70563-58-5)

Guidance literature:

Multi-step reaction with 3 steps

1: CH₂Cl₂ / 0.67 h / 20 °C

2: K₂CO₃; MeOH / 1.5 h / 20 °C

3: 2.9 mg / aq. cerium ammonium nitrate / acetonitrile / 1 h / -10 °C

With methanol; ammonium cerium(IV) nitrate; potassium carbonate; In dichloromethane; acetonitrile;

DOI:10.1021/ol062642i

Reference yield:

9-(tert-butyl-dimethyl-silanyloxy)-8,13,14,17,20,22-hexamethoxy-4,10,12,16-tetramethyl-2-aza-bicyclo[16.3.1]docosa-1(21),4,6,10,18(22),19-hexaen-3-one (137868-19-0) → herbimycin A (70563-58-5)

Guidance literature:

Multi-step reaction with 3 steps

1.1: 73 percent / tetrabutylammonium fluoride / tetrahydrofuran / 52 h / 20 °C

2.1: CH₂Cl₂ / 0.17 h / 20 °C

2.2: 97 percent / K₂CO₃ / methanol / 1.25 h

3.1: 63 percent / aq. ceric ammonium nitrate / acetonitrile / 0.17 h / -10 °C

With ammonium cerium(IV) nitrate; tetrabutyl ammonium fluoride; In tetrahydrofuran; dichloromethane; acetonitrile;

DOI:10.1021/ol036092p

upstream raw materials:

carbamic acid-8,13,14,17,20,22-hexamethoxy-4,10,12,16-tetramethyl-3-oxo-2-aza-bicyclo[16.3.1]docosa-1⁽²¹⁾,4,6,10,18⁽²²⁾,19-hexaen-9-yl ester

N,N-diallyl-3-bromo-2,5-dimethoxyaniline

(4R,6S)-7-tert-butyldiphenylsilyloxy-4-methoxy-6-methylhept-2-ene

(2S,4S)-5-((tert-butyldiphenylsilyl)oxy)-2-methoxy-4-methylpentanal

Downstream raw materials:

C₃₀H₄₄N₂O₉

Herbimycin C

11-hydroxy-(11-demethoxy)herbimycin C

Refernces

• 1、 Canova, Sophie,Bellosta, Veronique,Bigot, Antony,Mailliet, Patrick,Mignani, Serge,Cossy, Janine. "Total synthesis of herbimycin A". . p. 145 - 148. Retrieved 2007/10/03.
• 2、 Carter, Kendra D.,Panek, James S.. "Total Synthesis of Herbimycin A". . p. 55 - 57. Retrieved 2007/10/03.