Dolastatin 10

Base Information

• Chemical Name: Dolastatin 10
• CAS No.: 110417-88-4
• Molecular Formula: C42H68 N6 O6 S
• Molecular Weight: 785.105
• UNII: EI946JT51X
• DSSTox Substance ID: DTXSID70911674
• Nikkaji Number: J359.711C
• Wikidata: Q27104943
• NCI Thesaurus Code: C1300
• Metabolomics Workbench ID: 133452
• ChEMBL ID: CHEMBL39541
• Mol file: 110417-88-4.mol

Synonyms:Deo-Dola 10;deo-dolastatin 10;dolastatin 10;isodolastatin 10;NSC 376128

Chemical Property of Dolastatin 10

Chemical Property:

• Vapor Pressure: 1.95E-33mmHg at 25°C
• Boiling Point: 903.6°Cat760mmHg
• PKA: 13.81±0.46(Predicted)
• Flash Point: 500.3°C
• PSA: 161.65000
• Density: 1.116g/cm³
• LogP: 5.91010
• Solubility.: ≥78.5 mg/mL in EtOH; insoluble in H2O; ≥67.2 mg/mL in DMSO
• XLogP3: 5.8
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 21
• Exact Mass: 784.49210508
• Heavy Atom Count: 55
• Complexity: 1220

Purity/Quality:

98%min ^*data from raw suppliers

Dolastatin10 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC(C)C(C(CC(=O)N1CCCC1C(C(C)C(=O)NC(CC2=CC=CC=C2)C3=NC=CS3)OC)OC)N(C)C(=O)C(C(C)C)NC(=O)C(C(C)C)N(C)C
• Isomeric SMILES: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C3=NC=CS3)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C
• Recent ClinicalTrials: Dolastatin 10 in Treating Patients With Metastatic Pancreatic Cancer

Technology Process of Dolastatin 10

There total 91 articles about Dolastatin 10 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: 97.0%

Dov-Val-Dil trifluoroacetate + (2R,3R)-3-methoxy-2-methyl-N-[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]-3-[(2S)-pyrrolidin-2-yl]propanamide, trifluoroacetic acid salt → dolastatin 10 (110417-88-4)

Guidance literature:

With triethylamine; diethyl dicarbonate; In 1,2-dimethoxyethane; 1.) 0 deg C, 1 h, 2.) r.t., 2 h;

DOI:10.1039/P19960000859

Reference yield: 90.0%

N,N-dimethyl-L-valine (2812-32-0) + (2S)-2-amino-N-[(3R,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-2-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]carbamoyl]ethyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide → dolastatin 10 (110417-88-4)

Guidance literature:

With 4-methyl-morpholine; diethyl dicarbonate; In N,N-dimethyl-formamide;

DOI:10.1016/S0040-4039(00)92123-3

Reference yield:

Boc-L-Pro-H (69610-41-9,117625-90-8) → dolastatin 10 (110417-88-4)

Guidance literature:

Multi-step reaction with 6 steps

1: 18 percent / LDA / tetrahydrofuran / 0.5 h / -78 °C

2: 41 percent / BF₃*OEt₂ / CH₂Cl₂

3: H₂ / 5percent Pd/C / 2-methyl-propan-2-ol; H₂O

4: benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate, iso-Pr₂NEt / acetonitrile

5: HCl / dioxane / 1 h / Ambient temperature

6: diethyl phosphorocyanidate, Et₃N / dimethylformamide

With hydrogenchloride; diethyl cyanophosphonate; boron trifluoride diethyl etherate; hydrogen; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; N-ethyl-N,N-diisopropylamine; lithium diisopropyl amide; palladium on activated charcoal; In tetrahydrofuran; 1,4-dioxane; dichloromethane; water; N,N-dimethyl-formamide; acetonitrile; tert-butyl alcohol;

DOI:10.1248/cpb.43.1706

upstream raw materials:

N,N-dimethyl-L-valine

tert-butyl (2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidine-1-carboxylate

(3R,4S,5S)-tert-butyl 4-((S)-2-((S)-2-(dimethylamino)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoate

(3R,4S,5S)-4-((S)-2-((S)-2-(dimethylamino)-3-methylbutanamido)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoic acid

Refernces

Synthesis and Evaluation of Dolastatin 10 Analogues Containing Heteroatoms on the Amino Acid Side Chains

10.1021/acs.jnatprod.7b00359

The research focuses on the synthesis and evaluation of dolastatin 10 analogues, which are of significant interest in cancer research due to their potent in vitro activity and potential use as payloads in antibody drug conjugates (ADCs). The study aims to modify the P2 subunit of the dolastatin 10 core scaffold by introducing heteroatoms to the P2 side chain, resulting in compounds that maintain potent in vitro activity. The most active compounds were found to contain azides in the P2 unit and required a phenylalanine-derived P5 subunit. The researchers synthesized a series of auristatins, which are derivatives of dolastatin 10, using various amino acids and chemical modifications, including amines, azides, oxygens, and thiols. Key chemicals used in the synthesis process included Fmoc-protected amino acids, CMPI (2-chloro-1-methylpyridinium iodide), HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate), TFA (trifluoroacetic acid), and other reagents for specific coupling and deprotection steps. The conclusions of the research indicated that the P2 side chain modifications could be active in vitro, but these modified compounds followed a different activity trend than valine-based P2 compounds, and the presence of an ester or amide at the P5 position was crucial for the activity of these molecules in vitro.