(2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoic acid

Base Information

• Chemical Name: (2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoic acid
• CAS No.: 1174764-12-5
• Molecular Formula: C₃₆H₅₅N₅O₅S
• Molecular Weight: 669.929
• Mol file: 1174764-12-5.mol

Synonyms:(2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoic acid

Chemical Property of (2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoic acid

Chemical Property:

Purity/Quality:

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

Technology Process of (2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoic acid

There total 23 articles about (2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoic acid 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: 91.0%

methyl (2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoate (1219930-75-2) → (2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoic acid (1174764-12-5)

Guidance literature:

With lithium hydroxide monohydrate; In tetrahydrofuran; water; at 23 ℃; for 24h;

DOI:10.1021/jacs.7b12692

Reference yield:

tert-butyl {(3R)-1-[4-(hydroxymethyl)-1,3-thiazol-2-yl]-4-methylpentan-3-yl}methylcarbamate → (2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoic acid (1174764-12-5)

Guidance literature:

Multi-step reaction with 8 steps

1.1: Dess-Martin periodane / dichloromethane / Inert atmosphere

2.1: 2-methyl-but-2-ene; sodium chlorite; sodium dihydrogen phosphate monohydrate / tetrahydrofuran; tert-butyl alcohol; water / 1 h / Inert atmosphere

3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 0.08 h / 0 °C / Inert atmosphere

3.2: Inert atmosphere

4.1: dichloromethane / 2 h / Inert atmosphere; Cooling with ice

5.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 18 h / Inert atmosphere; Cooling with ice

6.1: 2,2',2''-triaminotriethylamine / dichloromethane / 2 h / Inert atmosphere; Cooling with ice

7.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / Inert atmosphere; Cooling with ice

8.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 24 h / Inert atmosphere

With sodium chlorite; sodium dihydrogen phosphate monohydrate; 2-methyl-but-2-ene; lithium hydroxide monohydrate; 2,2',2''-triaminotriethylamine; Dess-Martin periodane; triethylamine; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In tetrahydrofuran; dichloromethane; water; N,N-dimethyl-formamide; tert-butyl alcohol;

DOI:10.1021/jacs.5b12557

Reference yield:

2-{(3R)-3-[(tert-butoxycarbonyl)(methyl)amino]-4-methylpentyl}-1,3-thiazole-4-carboxylic acid (1053805-76-7) → (2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoic acid (1174764-12-5)

Guidance literature:

Multi-step reaction with 6 steps

1.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 0.08 h / 0 °C / Inert atmosphere

1.2: Inert atmosphere

2.1: dichloromethane / 2 h / Inert atmosphere; Cooling with ice

3.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 18 h / Inert atmosphere; Cooling with ice

4.1: 2,2',2''-triaminotriethylamine / dichloromethane / 2 h / Inert atmosphere; Cooling with ice

5.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / Inert atmosphere; Cooling with ice

6.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 24 h / Inert atmosphere

With lithium hydroxide monohydrate; 2,2',2''-triaminotriethylamine; triethylamine; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In tetrahydrofuran; dichloromethane; water; N,N-dimethyl-formamide;

DOI:10.1021/jacs.5b12557

upstream raw materials:

methyl (2S,4R)-2-methyl-4-[({2-[(3R)-4-methyl-3-{methyl[(2S,3S)-3-methyl-2-({[(2R)-1-methylpiperidin-2-yl]carbonyl}amino)pentanoyl]amino}pentyl]-1,3-thiazol-4-yl}carbonyl)amino]-5-phenylpentanoate

(S)-2-<(tert-butoxycarbonyl)amino>-3-methylbutan-1-ol

[(2S)-2-(tert-butoxycarbonylamino)-3-methyl-butyl] methanesulfonate

(R)-3-<(tert-butoxycarbonyl)amino>-4-methylpentanenitrile

Downstream raw materials:

(2S,4R)-4-[((R)-2-{3-[methyl-(N-methyl-(R)-pipecolyl-(S)-isoleucyl)-amino]-4-methyl-pentyl}-thiazole-4-carbonyl)-amino]-2-methyl-5-phenyl-pentanoic acid trifluoroacetic acid salt

Refernces

Design, synthesis, and antitumor activity evaluation of pretubulysin analogs

10.1111/cbdd.13852

The research focuses on the design, synthesis, and antitumor activity evaluation of pretubulysin analogs, which are structurally simpler than the naturally occurring pretubulysin and exhibit potent biological activity against various tumor cell lines. The study aimed to overcome the commercialization challenges posed by the complex structure of pretubulysin by designing and synthesizing a series of 2-(3-(methylamino)propyl)thiazole-4-carboxamides. The antitumor activities of these compounds were screened using MCF-7 (breast cancer) and NCI-H157 (lung cancer) cell lines, with Taxol and pretubulysin serving as controls. The synthesis involved a three-step process, including cyclization, bromination, and a Witting reaction, followed by reduction and hydrolysis to yield the desired compounds. The synthesized compounds were characterized using NMR spectroscopy and high-resolution mass spectrometry (HRMS), and their cytotoxicity was assessed through a mitochondrial-dependent reduction of MTT to formazan, measured spectrophotometrically. Additionally, molecular docking studies were conducted to understand the compounds' interaction with tubulin, using the co-crystal structure of microtubules and tubulysin M. The experiments revealed that certain analogs, such as compounds 8c and 8h, exhibited antitumor activities comparable to those of Taxol, suggesting their potential as novel antitumor drugs.