Plitidepsin

Base Information

• Chemical Name: Plitidepsin
• CAS No.: 137219-37-5
• Molecular Formula: C₅₇H₈₇N₇O₁₅
• Molecular Weight: 1110.36
• Mol file: 137219-37-5.mol

Synonyms:15H-Pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosine,cyclic peptide deriv.; Aplidin; Aplidine; Dehydrodidemnin B; Plitidepsin

Chemical Property of Plitidepsin

Chemical Property:

• Melting Point: 152-160°
• Boiling Point: °Cat760mmHg
• PKA: 11.28±0.70(Predicted)
• Flash Point: °C
• Density: 1.24g/cm³

Purity/Quality:

99% ^*data from raw suppliers

APLIDINE 95.00% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: Plitidepsin is a cyclic depsipeptide that was first isolated from a Mediterranean marine tunicate (Aplidium albicans) and, at present, is manufactured by total synthesis and commercialized as Aplidin?. Its antitumor activity, observed in preclinical in vitro and in vivo studies has prompted numerous clinical trials to be conducted over the last 17 years, alone or in combination with other anticancer agents.
• Clinical Use: Plitidepsin is a cyclic depsipeptide isolated from the marine tunicate Aplidium albicans. Plitidepsin displays a broad spectrum of antitumor activities, inducing apoptosis by triggering mitochondrial cytochrome c release, initiating the Fas/ DC95, JNK pathway and activating caspase 3 activation. This agent also inhibits elongation factor 1-a, thereby interfering with protein synthesis, and induces G1 arrest and G2 blockade, thereby inhibiting tumor cell growth.A phase II prospective open-label study (Ferme et al. 2008 ) to evaluate its activity in patients with relapsed/ refractory non-cutaneous PTCL was conducted in 14 patients. They were treated with plitidepsin 3.2 mg/m 2 IV infusion over 1-h on days 1, 8 and 15 every 4 weeks. Eleven patients were evaluable when preliminary results were reported, one was too early and two were non-evaluable. One con fi rmed CR and 3 PR’s were observed with a 36% objective response rate. Median overall survival was 11 months.Plitidepsin was tolerable in this heavily pretreated population with low hematological toxicity. Transient but reversible ALT elevation was noticed in 7 patients.Future trials will establish its role in T-cell lymphoma.

Technology Process of Plitidepsin

There total 39 articles about Plitidepsin 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: 62.0%

1-pyruvyl-L-proline (76391-12-3) + C49H78N6O12*ClH → dehydrodidemnin B (137219-37-5)

Guidance literature:

With N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate; In dichloromethane; 1.) -5 deg C, 30 min, 2.) room temperature, 4 h;

DOI:10.1021/jo961932h

Reference yield:

(2S)-3-[4-(methyloxy)phenyl]-2-(methyl{[(phenylmethyl)oxy]carbonyl}amino)propanoic acid (118171-80-5) → dehydrodidemnin B (137219-37-5)

Guidance literature:

Multi-step reaction with 9 steps

1: 88 percent / DCC, DMAP / CH₂Cl₂ / 15 h / Ambient temperature

2: 72 percent / aq. HF / acetonitrile / 7 h / -25 - -15 °C

3: 1-hydroxybenzotriazole, N-<(1H-benzotriazol-1-yl)(dimethylamino)methylene>-N-methylmethanaminium hexafluorophosphate N-oxide, N,N-diisopropylethylamine / tetrahydrofuran / 4 h / -10 - -5 °C

4: 99 percent / H₂ / Pd/C / tetrahydrofuran / 3 h / 760 Torr / Ambient temperature

5: 76 percent / N-<(dimethylamino)-1H-1,2,3-triazolo<4,5-b>pyridin-1-ylmethylene>-N-methylmethanaminium hexafluorophosphate N-oxide, 1-hydroxy-7-azabenzotriazole, N,N-diisopropylethylamine / tetrahydrofuran / 17 h / Ambient temperature

6: aq. HCl / dioxane / 1 h / Ambient temperature

7: 1-hydroxybenzotriazole, (1H-benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate, diisopropylethylamine / CH₂Cl₂ / 0.67 h / Ambient temperature

8: 99 percent / aq. HCl / dioxane / 0.5 h

9: 62 percent / bromotripyrrolidinophosphonium hexafluorophosphate, diisopropylethylamine / CH₂Cl₂ / 1.) -5 deg C, 30 min, 2.) room temperature, 4 h

With hydrogenchloride; dmap; 1-hydroxy-7-aza-benzotriazole; N-<(1H-benzotriazol-1-yl)(dimethylamino)methylene>-N-methylmethanaminium hexafluorophosphate N-oxide; N-<(dimethylamino)-1H-1,2,3-triazolo<4,5-b>pyridin-1-ylmethylene>-N-methylmethanaminium hexafluorophosphate N-oxide; hydrogen fluoride; hydrogen; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate; palladium on activated charcoal; In tetrahydrofuran; 1,4-dioxane; dichloromethane; acetonitrile;

DOI:10.1021/jo961932h

Reference yield:

1-(tert-butoxycarbonyl)-L-proline (15761-39-4,59433-50-0) → dehydrodidemnin B (137219-37-5)

Guidance literature:

Multi-step reaction with 10 steps

1: 99 percent / DMAP, DCC / CH₂Cl₂ / 7 h / 0 °C

2: TFA / CH₂Cl₂ / 0.33 h

3: 76 percent / 1-hydroxybenzotriazole, N-<(1H-benzotriazol-1-yl)(dimethylamino)methylene>-N-methylmethanaminium hexafluorophosphate N-oxide, N,N-diisopropylethylamine / acetonitrile / 3 h / Ambient temperature

4: 78 percent / H₂ / Pd/C / tetrahydrofuran / 1 h / 760 Torr / Ambient temperature

5: 60 percent / DMAP*CF₃COOH, N,N'-diisopropylcarbodiimide / CHCl₃ / 1.) reflux, 8 h, 2.) room temperature, 16 h

6: 81 percent / aq. NH₄OAc, Zn / tetrahydrofuran / 24 h

7: 95 percent / H₂ / Pd/C / tetrahydrofuran / 4 h / 760 Torr / Ambient temperature

8: 28 percent / N-<(dimethylamino)-1H-1,2,3-triazolo<4,5-b>pyridin-1-ylmethylene>-N-methylmethanaminium hexafluorophosphate N-oxide, 1-hydroxy-7-azabenzotriazole, N,N-diisopropylethylamine / tetrahydrofuran / 3 h / 0 °C

9: 98 percent / 5 M HCl / dioxane / 1 h

10: 62 percent / bromotripyrrolidinophosphonium hexafluorophosphate, diisopropylethylamine / CH₂Cl₂ / 1.) -5 deg C, 30 min, 2.) room temperature, 4 h

With hydrogenchloride; dmap; 1-hydroxy-7-aza-benzotriazole; N-<(1H-benzotriazol-1-yl)(dimethylamino)methylene>-N-methylmethanaminium hexafluorophosphate N-oxide; N-<(dimethylamino)-1H-1,2,3-triazolo<4,5-b>pyridin-1-ylmethylene>-N-methylmethanaminium hexafluorophosphate N-oxide; ammonium acetate; hydrogen; benzotriazol-1-ol; 4-N,N-dimethylaminopyridine trifluoroacetate; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate; trifluoroacetic acid; diisopropyl-carbodiimide; zinc; palladium on activated charcoal; In tetrahydrofuran; 1,4-dioxane; dichloromethane; chloroform; acetonitrile;

DOI:10.1021/jo961932h

upstream raw materials:

1-pyruvyl-L-proline

1-(tert-butoxycarbonyl)-L-proline

benzyl (2S)-2-pyrrolidinecarboxylate hydrochloride

H-Pro-OTce

Refernces