Tuberostemonine

Base Information

• Chemical Name: Tuberostemonine
• CAS No.: 6879-01-2
• Molecular Formula: C₂₂H₃₃NO₄
• Molecular Weight: 375.508
• Hs Code.: 29399990
• Nikkaji Number: J37.093B
• Wikidata: Q27137722
• Metabolomics Workbench ID: 141558
• ChEMBL ID: CHEMBL517375
• Mol file: 6879-01-2.mol

Synonyms:tubero-stemonine;tuberostemonine

Chemical Property of Tuberostemonine

Chemical Property:

• Vapor Pressure: 2.52E-12mmHg at 25°C
• Melting Point: 86～88℃
• Refractive Index: 1.555
• Boiling Point: 554.2 °C at 760 mmHg
• PKA: 8.90±0.70(Predicted)
• Flash Point: 289 °C
• PSA: 55.84000
• Density: 1.19 g/cm³
• LogP: 2.95260
• Storage Temp.: 2-8°C(protect from light)
• XLogP3: 3.9
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 2
• Exact Mass: 375.24095853
• Heavy Atom Count: 27
• Complexity: 636

Purity/Quality:

98%,99%, ^*data from raw suppliers

Tuberostemonine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC1C2CCCCN3C2C(CC3C4CC(C(=O)O4)C)C5C1OC(=O)C5C
• Isomeric SMILES: CC[C@@H]1[C@H]2CCCCN3[C@H]2[C@H](C[C@H]3[C@@H]4C[C@@H](C(=O)O4)C)[C@@H]5[C@H]1OC(=O)[C@H]5C
• Description: This novel alkaloid has been isolated from Sternona sessilifolia and S. tuberosa and was first given the formula C19H29O4N, subsequently altered to that given above. It crystallizes in colourless needles from MeOH with 1 mole of solvent, m.p. 65-88°C (dec.) and has [α]D - 25.4° (Me2CO). It is a non-phenolic, tertiary base and yields a hydrobromide, m.p. 120°C (dec.) and a perchlorate, m.p. 242°C (dec.). The methiodide monohydrate has m.p. 236-8°C (dec.) and the methochloride, dihydrate, m.p. 172°C. A methosulphate has also been prepared, m.p. 253°C (dec.). The base is not hydrolyzed by acids but in the presence of excess PtO2 it gives the dihydro derivative, m.p. 133°C, furnishing a hydrochloride, m.p. 281 ° C. Oxidation with KMnO4 gives a C17 compound, whereas oxidation with silver oxide forms a neutral substance, C22H29O4N, m.p. 178°C which still contains the lactone groups and gives a positive Ehrlich pyrrole reaction.
• Uses: Tuberostemonine is elucidated as one of the major components of Radix Stemonae and has been shown to display therapeutic effects against cigarette smoke-induced acute lung inflammation.

Technology Process of Tuberostemonine

There total 29 articles about Tuberostemonine 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%

C22H31NO4 (486421-64-1) → (-)-tuberostemonine (6879-01-2)

Guidance literature:

With hydrogen; palladium on activated charcoal; In methanol; at 20 ℃; for 17h;

DOI:10.1021/ja044280k

Reference yield:

(2S,3aR,6S,7aR)-6-hydroxy-2,3,3a,6,7,7a-hexahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester (171523-46-9) → (-)-tuberostemonine (6879-01-2)

Guidance literature:

Multi-step reaction with 21 steps

1.1: 97 percent / imidazole; dimethylaminopyridine / CH₂Cl₂ / 2 h / 0 °C

2.1: 90 percent / triethylsilane; palladium(II) acetate; triethylamine / CH₂Cl₂ / 15 h / 20 °C

3.1: 96 percent / K₂CO₃ / toluene / 15 h / 60 °C

4.1: 96 percent / tetrabutylammonium fluoride / tetrahydrofuran / 3 h / 20 °C

5.1: 88 percent / 4-methylmorpholine N-oxide; tetrapropylammonium perruthenate / CH₂Cl₂ / 15 h / 20 °C

6.1: potassium bis(trimethylsilyl)amide / tetrahydrofuran / 0.08 h / -90 °C

6.2: 66 percent / tetrahydrofuran / 0.5 h / -90 °C

7.1: 92 percent / Grubb's 2nd generation catalyst / CH₂Cl₂ / 2 h / Heating

8.1: 91 percent / triethylamine / CH₂Cl₂ / 3 h / 20 °C

9.1: chlorotris(triphenylphosphine)rhodium(I); H₂ / CH₂Cl₂; ethanol / 15 h / 20 °C / 760 Torr

9.2: 89 percent / 1,8-diazabicyclo[5.4.0]undec-7-ene / CH₂Cl₂ / 3.5 h / 20 °C

10.1: cerium(III) chloride heptahydrate; sodium borohydride / tetrahydrofuran; methanol / 0.17 h / 0 °C

11.1: 1.0 g / imidazole; 4-(dimethylamino)pyridine / CH₂Cl₂ / 14 h / 20 °C

12.1: dimethylaluminum chloride / CH₂Cl₂; hexane / 1 h / 20 °C

12.2: 94 percent / CH₂Cl₂; hexane / 14 h / 20 °C

13.1: 4,4'-di-tert-butylbiphenyl; lithium / tetrahydrofuran / 0.5 h / -78 °C

13.2: 95 percent / tetrahydrofuran / 0.25 h / -78 °C

14.1: 80 percent / lithium tri-sec-butylborohydride / tetrahydrofuran / 17 h / -78 - -15 °C

15.1: 388 mg / p-toluenesulfonic acid monohydrate / methanol / 20 h / 20 °C

16.1: 65 percent / xylene / 19 h / 130 - 140 °C

17.1: 81 percent / acetonitrile; H₂O / 18 h / 0 °C

18.1: 27 percent / AIBN; α,α,α-trifluorotoluene / 95 °C

19.1: 85 percent / Grubb's 2nd generation catalyst; allyltritylamine; N,N-diisopropylethylamine / CH₂Cl₂ / 16 h / Heating

20.1: p-toluenesulfonic acid monohydrate / CH₂Cl₂ / 0.5 h / Heating

20.2: 81 percent / Grubb's 2nd generation catalyst / CH₂Cl₂ / 60 h / Heating

21.1: 97 percent / H₂ / Pd/C / methanol / 17 h / 20 °C

With 1H-imidazole; tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride; triethylsilane; dmap; sodium tetrahydroborate; Wilkinson's catalyst; cerium(III) chloride; tetrapropylammonium perruthennate; 2,2'-azobis(isobutyronitrile); α,α,α-trifluorotoluene; 4,4'-di-tert-butylbiphenyl; N-tritylprop-2-en-1-amine; tetrabutyl ammonium fluoride; hydrogen; palladium diacetate; dimethylaluminum chloride; lithium; potassium hexamethylsilazane; L-Selectride; potassium carbonate; toluene-4-sulfonic acid; 4-methylmorpholine N-oxide; triethylamine; N-ethyl-N,N-diisopropylamine; palladium on activated charcoal; In tetrahydrofuran; methanol; ethanol; hexane; dichloromethane; water; toluene; acetonitrile; xylene; 10.1: Luche reduction / 16.1: Eschenmoser-Claisen rearrangement;

DOI:10.1021/ja044280k

Reference yield:

(2S,7aS,8R,10aR,10bS)-8-Hydroxy-1,2,4,5,6,7,7a,8,10a,10b-decahydro-azepino[3,2,1-hi]indole-2-carboxylic acid methyl ester (486421-67-4) → (-)-tuberostemonine (6879-01-2)

Guidance literature:

Multi-step reaction with 11 steps

1.1: 1.0 g / imidazole; 4-(dimethylamino)pyridine / CH₂Cl₂ / 14 h / 20 °C

2.1: dimethylaluminum chloride / CH₂Cl₂; hexane / 1 h / 20 °C

2.2: 94 percent / CH₂Cl₂; hexane / 14 h / 20 °C

3.1: 4,4'-di-tert-butylbiphenyl; lithium / tetrahydrofuran / 0.5 h / -78 °C

3.2: 95 percent / tetrahydrofuran / 0.25 h / -78 °C

4.1: 80 percent / lithium tri-sec-butylborohydride / tetrahydrofuran / 17 h / -78 - -15 °C

5.1: 388 mg / p-toluenesulfonic acid monohydrate / methanol / 20 h / 20 °C

6.1: 65 percent / xylene / 19 h / 130 - 140 °C

7.1: 81 percent / acetonitrile; H₂O / 18 h / 0 °C

8.1: 27 percent / AIBN; α,α,α-trifluorotoluene / 95 °C

9.1: 85 percent / Grubb's 2nd generation catalyst; allyltritylamine; N,N-diisopropylethylamine / CH₂Cl₂ / 16 h / Heating

10.1: p-toluenesulfonic acid monohydrate / CH₂Cl₂ / 0.5 h / Heating

10.2: 81 percent / Grubb's 2nd generation catalyst / CH₂Cl₂ / 60 h / Heating

11.1: 97 percent / H₂ / Pd/C / methanol / 17 h / 20 °C

With 1H-imidazole; tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride; dmap; 2,2'-azobis(isobutyronitrile); α,α,α-trifluorotoluene; 4,4'-di-tert-butylbiphenyl; N-tritylprop-2-en-1-amine; hydrogen; dimethylaluminum chloride; lithium; L-Selectride; toluene-4-sulfonic acid; N-ethyl-N,N-diisopropylamine; palladium on activated charcoal; In tetrahydrofuran; methanol; hexane; dichloromethane; water; acetonitrile; xylene; 6.1: Eschenmoser-Claisen rearrangement;

DOI:10.1021/ja044280k

upstream raw materials:

C₂₂H₃₁NO₄

(2S,3aR,6S,7aR)-6-hydroxy-2,3,3a,6,7,7a-hexahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester

(2S,3aR,7aR)-3a-hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester

<2S-(2β,3aβ,7aβ)>-2,3,3a,6,7,7a-hexahydro-3a-benzoyloxy-6-oxo-1H-indole-1,2-dicarboxylic acid 1-benzyl 2-methyl ester

Downstream raw materials:

didehydrotuberostemonine

(3aS,12aS)-5c-ethyl-4t-hydroxy-3t-methyl-11c-((2S)-4c-methyl-5-oxo-tetrahydro-[2r]furyl)-(3ar)-3,3a,4,5,6,7,8,9,11,12-decahydro-azepino[3,2,1-hi]furo[2,3-d]indole

Refernces

• 1、 Wipf, Peter,Rector, Stacey R.,Takahashi, Hidenori. "Total synthesis of (-)-tuberostemonine". . p. 14848 - 14849. Retrieved 2007/10/03.