Apratoxin A

Base Information

• Chemical Name: Apratoxin A
• CAS No.: 350791-64-9
• Molecular Formula: C45H69N5O8S
• Molecular Weight: 840.138
• DSSTox Substance ID: DTXSID5040419
• Nikkaji Number: J1.570.134J
• Wikipedia: Apratoxin_A
• Wikidata: Q4781819
• Metabolomics Workbench ID: 55078
• ChEMBL ID: CHEMBL501696
• Mol file: 350791-64-9.mol

Synonyms:apratoxin A

Chemical Property of Apratoxin A

Chemical Property:

• Vapor Pressure: 0mmHg at 25°C
• Boiling Point: 993.7°Cat760mmHg
• Flash Point: 554.8°C
• PSA: 183.45000
• Density: 1.22g/cm³
• LogP: 4.85660
• XLogP3: 6.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 6
• Exact Mass: 839.48668535
• Heavy Atom Count: 59
• Complexity: 1560

Purity/Quality:

99% ^*data from raw suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC(C)C1C(=O)N2CCCC2C(=O)OC(CC(CC(C(C3=NC(CS3)C=C(C(=O)NC(C(=O)N(C(C(=O)N1C)C)C)CC4=CC=C(C=C4)OC)C)C)O)C)C(C)(C)C
• Isomeric SMILES: CC[C@H](C)[C@H]1C(=O)N2CCC[C@H]2C(=O)O[C@@H](C[C@H](C[C@@H]([C@@H](C3=N[C@H](CS3)/C=C(/C(=O)N[C@H](C(=O)N([C@H](C(=O)N1C)C)C)CC4=CC=C(C=C4)OC)\C)C)O)C)C(C)(C)C

Technology Process of Apratoxin A

There total 96 articles about Apratoxin 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:

pyrrolidine-2-carboxylic acid 1-tert-butyl-6-(4-{2-[1-({1-[(1-carboxy-2-methyl-butyl)-methyl-carbamoyl]-ethyl}-methyl-carbamoyl)-2-(4-methoxy-phenyl)-ethylcarbamoyl]-propenyl}-4,5-dihydro-thiazol-2-yl)-5-hydroxy-3-methyl-heptyl ester (878626-86-9) → (-)-apratoxin A (350791-64-9)

Guidance literature:

With 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 dichloromethane; at 20 ℃; for 22h;

DOI:10.1021/ol052907d

Reference yield:

(S)-5,5-dimethyl-4-hydroxyhexan-2-one (197454-20-9) → (-)-apratoxin A (350791-64-9)

Guidance literature:

Multi-step reaction with 28 steps

1.1: 15 g / imidazole / dimethylformamide / 24 h

2.1: NaBH₄ / methanol / 0.5 h

3.1: Et₃N / CH₂Cl₂ / 2 h / 0 °C

4.1: 10 g / tBuOK / toluene / 1 h / Heating

5.1: ozone / CH₂Cl₂ / -78 - 20 °C

5.2: Me₂S / CH₂Cl₂ / 24 h / 40 °C

6.1: n-butyllithium; diisopropylamine / hexane; tetrahydrofuran / 0.33 h / -78 °C

6.2: hexane; tetrahydrofuran / 1 h

7.1: aq. HF / acetonitrile / 20 °C

8.1: 1.75 g / Et₃N; MsCl / CH₂Cl₂ / 2 h

9.1: 94 percent / CuCN / diethyl ether; diethyl ether / 1 h

10.1: LiAlH₄ / tetrahydrofuran / 1 h / Heating

11.1: pyridine / CH₂Cl₂

12.1: K₂CO₃ / methanol; H₂O / 5 h

13.1: 2.3 g / Dess-Martin reagent / CH₂Cl₂ / 3 h

14.1: CF₃SO₃H; Et₃B; DIPEA / hexane; CH₂Cl₂ / 0.5 h / -10 °C

14.2: 90 percent / TiCl₄ / hexane; CH₂Cl₂ / 2 h

15.1: LiAlH₄ / tetrahydrofuran / 0.5 h / Heating

16.1: 1.05 g / PPTs / 24 h

17.1: 90 percent / 2,4,6-trichlorobenzoyl chloride; DIPEA; DMAP / benzene

18.1: TsOH / methanol

19.1: 2,2,6,6-tetramethylpiperidinyloxyl; KBr; NaHCO₃ / NaClO / CH₂Cl₂; H₂O / 1 h

20.1: 155 mg / NaClO₂; NaH₂PO₄ / H₂O; 2-methyl-propan-2-ol; various solvent(s) / 1 h

21.1: 237 mg / HATU; DIPEA / CH₂Cl₂ / 12 h / 20 °C

22.1: 81 percent / DIPEA / CH₂Cl₂ / 1.5 h

23.1: 92 percent / trifluoromethanesulfonic anhydride; triphenylphosphine oxide / CH₂Cl₂ / 1 h / 0 °C

24.1: TMSOTf / CH₂Cl₂ / 1 h

25.1: 38 mg / HATU; DIPEA / CH₂Cl₂ / 20 °C

26.1: tetrabutylammonium fluoride / tetrahydrofuran

27.1: 10 mg / HATU; DIPEA / CH₂Cl₂ / 72 h / 20 °C

28.1: 7 mg / KCN / ethanol / 50 °C

With pyridine; 1H-imidazole; dmap; potassium cyanide; sodium chlorite; sodium tetrahydroborate; sodium dihydrogenphosphate; lithium aluminium tetrahydride; n-butyllithium; 4-oxo-2,2,6,6-tetramethylpiperidin-oxyl; triethyl borane; trifluorormethanesulfonic acid; trimethylsilyl trifluoromethanesulfonate; 2,4,6-trichlorobenzoyl chloride; hydrogen fluoride; potassium tert-butylate; tetrabutyl ammonium fluoride; pyridinium p-toluenesulfonate; sodium hydrogencarbonate; potassium carbonate; Dess-Martin periodane; toluene-4-sulfonic acid; ozone; methanesulfonyl chloride; trifluoromethanesulfonic acid anhydride; triethylamine; diisopropylamine; N-ethyl-N,N-diisopropylamine; Triphenylphosphine oxide; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; potassium bromide; sodium hypochlorite; In tetrahydrofuran; methanol; diethyl ether; ethanol; hexane; dichloromethane; water; N,N-dimethyl-formamide; toluene; acetonitrile; tert-butyl alcohol; benzene; 13.1: Dess-Martin oxidation;

DOI:10.1002/chem.200600599

Reference yield:

pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (2S)-2-[(1S,3S,5S,6S,8R)-1-tert-butyl-5-(tert-butyldimethylsilyloxy)-6-carboxy-3-methylheptyl] ester (582321-68-4) → (-)-apratoxin A (350791-64-9)

Guidance literature:

Multi-step reaction with 12 steps

1: 372 mg / iPr₂NEt; HATU / CH₂Cl₂ / 10 h / 20 °C

2: 95 percent / TBAF / tetrahydrofuran / 0.33 h / 0 °C

3: 2,6-lutidine; TMDOTf / CH₂Cl₂ / 0.5 h / 20 °C

4: 359 mg / iPr₂NEt / CH₂Cl₂; tetrahydrofuran / 0.67 h / 0 °C

5: 84 percent / pyridine; DMAP / CH₂Cl₂ / 1 h / 20 °C

6: PPh₃O; Tf₂O / CH₂Cl₂ / 0.5 h / 0 °C

7: 28.2 mg / aq. NH₄OAc; Zn / tetrahydrofuran / 20 °C

8: 95 percent / N-methylaniline / Pd(PPh₃)4 / tetrahydrofuran / 0.67 h / 20 °C

9: 30.7 mg / iPr₂NEt; HATU / CH₂Cl₂ / 8 h / 20 °C

10: N-methylaniline / Pd(PPh₃)4 / tetrahydrofuran / 0.25 h / 20 °C

11: Et₂NH / acetonitrile / 0.5 h / 20 °C

12: 14.5 mg / iPr₂NEt; HATU / CH₂Cl₂ / 22 h / 20 °C

With pyridine; 2,6-dimethylpyridine; dmap; trifluoromethylsulfonic anhydride; TMDOTf; ammonium acetate; tetrabutyl ammonium fluoride; diethylamine; N-ethyl-N,N-diisopropylamine; N-methylaniline; Triphenylphosphine oxide; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; zinc; tetrakis(triphenylphosphine) palladium⁽⁰⁾; In tetrahydrofuran; dichloromethane; acetonitrile;

DOI:10.1021/ol052907d

upstream raw materials:

pyrrolidine-2-carboxylic acid 1-tert-butyl-6-(4-{2-[1-({1-[(1-carboxy-2-methyl-butyl)-methyl-carbamoyl]-ethyl}-methyl-carbamoyl)-2-(4-methoxy-phenyl)-ethylcarbamoyl]-propenyl}-4,5-dihydro-thiazol-2-yl)-5-hydroxy-3-methyl-heptyl ester

(E)-(S)-4-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-methyl-5-tritylsulfanyl-pent-2-enoic acid 3-methyl-but-2-enyl ester

(S)-Pyrrolidine-1,2-dicarboxylic acid 2-((1S,3S,5S,6S)-5-acetoxy-1-tert-butyl-3-methyl-6-{(S)-4-[(E)-2-(3-methyl-but-2-enyloxycarbonyl)-propenyl]-4,5-dihydro-thiazol-2-yl}-heptyl) ester 1-(9H-fluoren-9-ylmethyl) ester

(S)-Pyrrolidine-1,2-dicarboxylic acid 2-{(1S,3S,5S,6S)-5-acetoxy-1-tert-butyl-3-methyl-6-[(E)-(S)-3-(3-methyl-but-2-enyloxycarbonyl)-1-tritylsulfanylmethyl-but-2-enylcarbamoyl]-heptyl} ester 1-(9H-fluoren-9-ylmethyl) ester