CID 3199

Base Information

• Chemical Name: CID 3199
• CAS No.: 114899-77-3
• Molecular Formula: C39H43N3O11S
• Molecular Weight: 761.85
• European Community (EC) Number: 695-026-8
• DSSTox Substance ID: DTXSID30861227
• Wikipedia: Trabectedin
• Wikidata: Q105210697
• Mol file: 114899-77-3.mol

Synonyms:ecteinascidin 743;ET 743;ET-743;ET743;NSC 684766;trabectedin;Yondelis

Chemical Property of CID 3199

Chemical Property:

• PKA: 9.73±0.40(Predicted)
• PSA: 194.02000
• Density: 1.53g/cm³
• LogP: 3.61780
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 3.4
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 15
• Rotatable Bond Count: 4
• Exact Mass: 761.26183037
• Heavy Atom Count: 54
• Complexity: 1450

Purity/Quality:

99.5% ^*data from raw suppliers

Trabectedin ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=CC2=C(C3C4C5C6=C(C(=C7C(=C6C(N4C(C(C2)N3C)O)COC(=O)C8(CS5)C9=CC(=C(C=C9CCN8)O)OC)OCO7)C)OC(=O)C)C(=C1OC)O
• Recent ClinicalTrials: Ecteinascidin 743 in Treating Children With Refractory Solid Tumors
• Recent EU Clinical Trials: A Randomized Multicenter Phase 3 Study of Milademetan Versus Trabectedin in Patients with Dedifferentiated Liposarcoma
• Description: Trabectedin is a marine natural product derived from the tunicate Ecteinascidia turbinate. With its demonstrated in vitro and in vivo activity against a range of solid tumor cell lines, human xenografts and tumor explants, this antineoplastic agent has been developed and launched for the treatment of advanced STS after failure of first-line therapy with anthracyclines or ifosfamide or in patients who are unsuited to receive these agents. Its proposed mechanism of action involves binding to the N2 position of guanine in the minor groove demonstrating a preference for sequences containing 5′-PuGC and 5′-PyGG motifs. Subsequent alkylation of DNA, via an iminium intermediate generated from an intra-molecular acid-catalyzed activation and dehydration of the carbinolamine, induces a curvature of the DNA toward the major groove that ultimately disrupts the binding of transcription factors involved in cell proliferation. Evaluation of trabectedin against the National Cancer Institute’s human in vitro cell line panel, including melanoma, non-small-cell lung, ovarian, renal, prostate, and breast cancer, demonstrated potencies ranging from 1 pM to 10 nM.
• Uses: A tetrahydroisoquinoline alkaloid with antitumor activity isolated from the Caribbean tunicate, Ecteinascidin turbinata. It is the first marine anticancer agent approved in the European Union for patients with soft tissue sarcoma (STS). A tetrahydroisoquinoline alkaloid with antitumor activity isolated from the Caribbean tunicate, Ecteinascidin turbinata. It is the first marine anticancer agent approved in the European Union for patients with soft tissue sarcoma (STS). Antineoplastic.
• Clinical Use: Antineoplastic agent: Advanced soft tissue sarcoma Ovarian cancer
• Drug interactions: Potentially hazardous interactions with other drugs Alcohol: Avoid concomitant use. Antibacterials: concentration reduced by rifampicin. Antipsychotics: avoid with clozapine, increased risk of agranulocytosis. Vaccines: risk of generalised infections - avoid.

Technology Process of CID 3199

There total 194 articles about CID 3199 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: 96.9%

(1'R,6R,6aR,7R,13S,14R,16R)-5-(acetyloxy)-3',4',6,6a,7,13,14,16-octahydro-6',8-dihydroxy-7',9-dimethoxy-4,10,23-trimethyl-19-oxo-spiro[6,16-(epithiopropanoxymethano)-7,13-imino-12H-1,3-dioxolo[7,8]isoquino[3,2-b][3]benzazocine-20,1'(2'H)-isoquinoline]-14-carbonitrile (114899-80-8) → ecteinascidin 743 (114899-77-3)

Guidance literature:

With silver nitrate; In water; acetonitrile; at 20 ℃; for 11h;

DOI:10.1021/np010485k

Reference yield:

(1'R,6R,6aR,7R,13S,14R,16R)-5-(acetyloxy)-3',4',6,6a,7,13,14,16-octahydro-6'-hydroxy-7',9-dimethoxy-8-(methoxymethoxy)-4,10,23-trimethyl-19-oxo-spiro[6,16-(epithiopropanoxymethano)-7,13-imino-12H-1,3-dioxolo[7,8]isoquino[3,2-b][3]benzazocine-20,1'(2'H)-isoquinoline]-14-carbonitrile (203922-37-6) → ecteinascidin 743 (114899-77-3)

Guidance literature:

Multi-step reaction with 2 steps

1: aq. CF₃COOH / tetrahydrofuran / 9 h / 23 °C

2: aq. AgNO₃ / acetonitrile / 11 h / 23 °C

With silver nitrate; trifluoroacetic acid; In tetrahydrofuran; acetonitrile;

DOI:10.1021/ja962480t

Reference yield:

3,4-(methylenedioxy)phenyl methoxymethyl ether (111726-43-3) → ecteinascidin 743 (114899-77-3)

Guidance literature:

Multi-step reaction with 25 steps

1.1: n-BuLi; B(OMe)3 / tetrahydrofuran

1.2: 95 percent / AcOH; H₂O₂ / 0 - 20 °C

2.1: 97 percent / LiCl; 3 Angstroem molecular sieves / toluene; various solvent(s) / 24 h / 20 °C

3.1: 95 percent / K₂CO₃ / dimethylformamide / 1 h / 23 °C

4.1: 93 percent / K₃PO₄; Pd(PPh₃)4 / dioxane / 4 h / 100 °C

5.1: 91 percent / benzotriazole; thionyl bromide / CH₂Cl₂ / 0.33 h / 20 °C

6.1: 68 percent / triethylamine / acetonitrile / 14 h / 0 °C

7.1: 97 percent / imidazole / dimethylformamide / 3 h / 23 °C

8.1: 94 percent / K₂CO₃; MeOH / 2 h / 23 °C

9.1: Dess-Martin periodinane / CH₂Cl₂ / 0.33 h / 23 °C

10.1: 1.26 g / ZnCl₂ / CH₂Cl₂; tetrahydrofuran / 0.17 h / 23 °C

11.1: 80 percent / LiBH₄ / tetrahydrofuran; methanol / 10 h / 0 °C

12.1: 92 percent / pyridine; DMAP / CH₂Cl₂ / 0.5 h / 23 °C

13.1: 91 percent / aq. HF / acetonitrile / 2 h / 23 °C

14.1: 93 percent / Dess-Martin periodinane / CH₂Cl₂ / 0.33 h / 20 °C

15.1: 95 percent / CF₃COOH / CH₂Cl₂ / 0.5 h / 23 °C

16.1: 96 percent / K₂CO₃; MeOH / 1 h / 20 °C

17.1: 95 percent / DMAP; EDCl / CH₂Cl₂ / 1 h / 20 °C

18.1: CF₃COOH / 2,2,2-trifluoro-ethanol / 3 h / 20 °C

19.1: 143 mg / pyridine; DMAP / CH₂Cl₂ / 0.5 h / 23 °C

20.1: 87 percent / n-Bu₃SnH; AcOH; Pd(PPh₃)2Cl₂ / CH₂Cl₂ / 0.33 h / 20 °C

21.1: 97 percent / NaBH₃CN; AcOH / acetonitrile; methanol / 2 h / 23 °C

22.1: 92 percent / Zn; AcOH / diethyl ether / 1 h / 23 °C

23.1: 4-formyl-1-methylpyridinium benzenesulfonate / CH₂Cl₂; dimethylformamide / 0.17 h / 23 °C

23.2: DBU / CH₂Cl₂; dimethylformamide / 0.25 h / 23 °C

23.3: 53 percent / aq. oxalic acid / CH₂Cl₂; dimethylformamide / 0.5 h / 23 °C

24.1: 97 percent / NaOAc / ethanol / 3 h / 23 °C

25.1: 92 percent / aq. AgNO₃ / acetonitrile / 19 h / 23 °C

With pyridine; 1H-imidazole; methanol; dmap; 1,2,3-Benzotriazole; bis-triphenylphosphine-palladium(II) chloride; potassium phosphate; lithium borohydride; sulfurous dibromide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; n-butyllithium; Trimethyl borate; 3 A molecular sieve; hydrogen fluoride; tri-n-butyl-tin hydride; sodium acetate; sodium cyanoborohydride; potassium carbonate; Dess-Martin periodane; silver nitrate; acetic acid; N-methylpyridinium-4-carboxaldehyde benzenesulfonate salt; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; trifluoroacetic acid; lithium chloride; zinc(II) chloride; zinc; In tetrahydrofuran; 1,4-dioxane; methanol; diethyl ether; ethanol; dichloromethane; 2,2,2-trifluoroethanol; N,N-dimethyl-formamide; toluene; acetonitrile; 2.1: Friedel-Crafts reaction / 4.1: Suzuki-Miyaura cross-coupling reaction / 9.1: Dess-Martin oxidation / 10.1: Strecker reaction / 14.1: Dess-Martin oxidation / 15.1: Pomerantz-Frisch-type cyclization / 24.1: Pictet-Spengler reaction;

DOI:10.1021/ja0571794

upstream raw materials:

(1'R,6R,6aR,7R,13S,14R,16R)-5-(acetyloxy)-3',4',6,6a,7,13,14,16-octahydro-6',8-dihydroxy-7',9-dimethoxy-4,10,23-trimethyl-19-oxo-spiro[6,16-(epithiopropanoxymethano)-7,13-imino-12H-1,3-dioxolo[7,8]isoquino[3,2-b][3]benzazocine-20,1'(2'H)-isoquinoline]-14-carbonitrile

5-(2-amino-ethyl)-2-methoxy-phenol

ethyl 2-bromo-2-(6-(methoxymethoxy)-7-methylbenzo[d][1,3]dioxol-4-yl)acetate

ethyl 2-hydroxy-2-(6-(methoxymethoxy)-7-methylbenzo[d][1,3]dioxol-4-yl)acetate

Downstream raw materials:

ecteinascidin 770

Refernces

• 1、 Suwanborirux, Khanit,Charupant, Kornvika,Amnuoypol, Surattana,Pummangura, Sunibhond,Kubo, Akinori,Saito, Naoki. "Ecteinascidins 770 and 786 from the Thai tunicate Ecteinascidia thurstoni". . p. 935 - 937. Retrieved 2002.
• 2、 -. "PREPARATION METHOD FOR ECTEINASCIDIN COMPOUND AND INTERMEDIATE THEREOF". Paragraph 0111-0113. . Retrieved 2021/11/20.
• 3、 -. "PROCESS FOR THE PREPARATION OF ECTEINASCIDIN DERIVATIVE AND ITS INTERMEDIATE". Page/Page column 15-16; 19. . Retrieved 2020/06/10.