2-[(4Z,6E)-7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxo-1-oxacyclooctadeca-4,6-dien-2-yl]cyclopentane-1-carboxylic acid

Base Information

• Chemical Name: 2-[(4Z,6E)-7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxo-1-oxacyclooctadeca-4,6-dien-2-yl]cyclopentane-1-carboxylic acid
• CAS No.: 7184-60-3
• Molecular Formula: C28H43NO6
• Molecular Weight: 489.653
• Hs Code.: 29419090
• European Community (EC) Number: 811-923-0
• Metabolomics Workbench ID: 108174
• Wikipedia: Borrelidin
• Mol file: 7184-60-3.mol

Synonyms:borrelidin

Chemical Property of 2-[(4Z,6E)-7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxo-1-oxacyclooctadeca-4,6-dien-2-yl]cyclopentane-1-carboxylic acid

Chemical Property:

• Appearance/Colour: White to off-white powder
• Vapor Pressure: 2.6E-23mmHg at 25°C
• Melting Point: 143-145℃
• Refractive Index: 1.538
• Boiling Point: 710.3 °C at 760 mmHg
• PKA: 4.56±0.40(Predicted)
• Flash Point: 383.4 °C
• PSA: 127.85000
• Density: 1.14 g/cm³
• LogP: 4.63558
• Storage Temp.: −20°C
• Solubility.: DMSO: 1 mg/mL
• XLogP3: 5.6
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 2
• Exact Mass: 489.30903809
• Heavy Atom Count: 35
• Complexity: 827

Purity/Quality:

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

Borrelidin ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CC1CC(CC(C(C(=CC=CCC(OC(=O)CC(C(C1)C)O)C2CCCC2C(=O)O)C#N)O)C)C
• Isomeric SMILES: CC1CC(CC(C(/C(=C/C=C\CC(OC(=O)CC(C(C1)C)O)C2CCCC2C(=O)O)/C#N)O)C)C
• Description: Borrelidin (7184-60-3) ia a novel macrolide which inhibits bacterial and eukaryotic threonyl-tRNA synthetase.1 Displays potent anti-angiogenic activity (IC50=0.8 nM) and induces the collapse of newly formed capillary tubules.2 Modulates alternative splicing of VEGF in favor of anti-angiogenic isoforms.3 Induces apoptosis in ALL cell lines.4 Induces unfolded protein response in oral cancer cells.5 Cell permeable.
• Uses: Borrelidin is an unusual nitrile-containing metabolite isolated from Streptomyces. Originally discovered as active against Borrelia species, borrelidin has since found a role as a selective inhibitor of bacterial and eukaryal threonyl-tRNA synthetase. More recent research has found that borrelidin is a very potent angiogenesis inhibitor and induces apoptosis of the capillary tube-forming cells. Borrelidin is an important lead for antimalarial discovery, displaying activity against drug-resistant Plasmodia. Borrelidin is a secondary metabolite produced by Streptomyces and other bacteria. It displays potent antiangiogenic activity, preventing tube formation in rat aorta explants (IC50 = 0.8 nM) and inducing apoptosis in endothelial cells. Borrelidin also alters the splicing of VEGF mRNA, producing an antiangiogenic isoform of the growth factor. It has long been known as a powerful inhibitor of both eukaryotic and bacterial threonyl tRNA synthetase. Borrelidin is also an effective anti-malarial drug, as it kills P. falciparum with an IC50 value of 1.8 nM. At higher doses, it inhibits cyclin-dependent kinase in yeast (IC50 = 24 μM), resulting in growth arrest in the G1 phase.

Technology Process of 2-[(4Z,6E)-7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxo-1-oxacyclooctadeca-4,6-dien-2-yl]cyclopentane-1-carboxylic acid

There total 142 articles about 2-[(4Z,6E)-7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxo-1-oxacyclooctadeca-4,6-dien-2-yl]cyclopentane-1-carboxylic 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: 94.0%

(1'R,1S,2S,2'R,8R,9S,11R,13S,15S,16S)-2-(7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxo-oxacyclooctadeca-4,6-dien-2-yl)-cyclopentane-1'-carboxylic acid 2-trimethylsilanyl-ethyl ester (631919-63-6) → borrelidin (7184-60-3,97328-74-0)

Guidance literature:

With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 0 ℃; for 2h;

DOI:10.1021/ja030139k

Reference yield:

(1R,2R)-1,2-(dihydroxymethyl)cyclopentane (57287-24-8) → borrelidin (7184-60-3,97328-74-0)

Guidance literature:

Multi-step reaction with 26 steps

1.1: NaH / dimethylformamide / -20 - 20 °C

2.1: 6.24 g / Dess-Martin periodinane / CH₂Cl₂ / 0.5 h / 20 °C

3.1: 54 percent / tetrahydrofuran / 0.5 h / -78 °C

4.1: 99 percent / 2,6-lutidine / CH₂Cl₂ / 1 h / 0 °C

5.1: H₂O; NMO; OsO₄ / acetone / 4 h / 20 °C

6.1: 533 mg / NaIO₄; H₂O / methanol / 2 h / 0 °C

7.1: 73 percent / benzene / 48 h / 80 °C

8.1: 84 percent / benzene / 39 h / 70 °C

9.1: 96 percent / HF*pyridine; pyridine / tetrahydrofuran / 228 h / 20 °C

10.1: 452 mg / Et₃N; DMAP / benzene / 2 h / 20 °C

11.1: 96 percent / PPTS / ethanol / 16 h / 50 °C

12.1: TPAP; NMO; 4 Angstroem molecular sieves / CH₂Cl₂ / 1.5 h / 20 °C

13.1: SmI₂ / tetrahydrofuran / 1 h / -78 °C

13.2: Dess-Martin periodinane / CH₂Cl₂ / 0.5 h / 20 °C

14.1: DMAP / pentane / 168 h / 20 °C

14.2: 31.2 mg / NaBH₄; CeCl₃*7H₂O / methanol / 0.5 h / 0 °C

15.1: 85 percent / 2,6-lutidine / CH₂Cl₂ / 0.5 h / 0 °C

16.1: 85 percent / NaBH₄ / Pd(PPh₃)4 / methanol / 0.5 h / 0 °C

17.1: 69 percent / NH₃; Et₃N; BOP / dioxane; tetrahydrofuran / 48 h / 23 °C

18.1: 31 percent / 2-chloro-1,3-dimethylimidazolinium chloride / CH₂Cl₂ / 1.5 h / 20 °C

19.1: 73 percent / K₂CO₃; MeOH / 1.5 h / 20 °C

20.1: Dess-Martin periodinane / CH₂Cl₂ / 0.5 h / 20 °C

21.1: 8.50 mg / NaBH₄; CeCl₃*7H₂O / methanol / 0.08 h / 0 °C

22.1: 75 percent / 2,6-lutidine / CH₂Cl₂ / 1 h / 0 °C

23.1: 90 percent / DDQ; H₂O / CH₂Cl₂ / 0.25 h / 0 °C

24.1: Dess-Martin periodinane / CH₂Cl₂ / 0.5 h / 20 °C

25.1: NaClO₂; NaH₂PO₄*2H₂O; 2-methyl-2-butene / 2-methyl-propan-2-ol; H₂O / 0.5 h / 20 °C

26.1: 5.20 mg / HF*pyridine; pyridine / tetrahydrofuran / 48 h / 20 °C

With pyridine; 2,6-dimethylpyridine; methanol; dmap; sodium chlorite; sodium tetrahydroborate; sodium periodate; sodium dihydrogenphosphate; osmium(VIII) oxide; N-methyl-2-indolinone; samarium diiodide; cerium(III) chloride; tetrapropylammonium perruthennate; 2-methyl-but-2-ene; 4 A molecular sieve; ammonia; water; pyridinium p-toluenesulfonate; 2-chloro-1,3-dimethylimidazolinium chloride; sodium hydride; potassium carbonate; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; Dess-Martin periodane; pyridine hydrogenfluoride; triethylamine; 2,3-dicyano-5,6-dichloro-p-benzoquinone; tetrakis(triphenylphosphine) palladium⁽⁰⁾; In tetrahydrofuran; 1,4-dioxane; methanol; ethanol; dichloromethane; water; N,N-dimethyl-formamide; acetone; tert-butyl alcohol; pentane; benzene; 2.1: Dess-Martin oxidation / 7.1: Wittig reaction / 8.1: Wittig reaction / 13.2: Dess-Martin oxidation / 20.1: Dess-Martin oxidation / 24.1: Dess-Martin oxidation;

DOI:10.1021/jo062089i

Reference yield:

(2R,4S)-1-hydroxy-2,4-dimethylpentyl acetate (90270-02-3,97937-36-5) → borrelidin (7184-60-3,97328-74-0)

Guidance literature:

Multi-step reaction with 34 steps

1.1: 98 percent / imidazole / CH₂Cl₂ / 0.5 h / 20 °C

2.1: 98 percent / K₂CO₃; MeOH / 2 h / 20 °C

3.1: imidazole / dimethylformamide / 0 - 20 °C

4.1: 4.19 g / PPTS; EtOH / 7 h / 50 °C

5.1: 88 percent / TPAP; 4 Angstroem molecular sieves; NMO / CH₂Cl₂ / 0.5 h / 20 °C

6.1: n-BuLi / tetrahydrofuran; hexane / -78 - -40 °C

6.2: tetrahydrofuran; hexane / 1 h / -30 °C

6.3: tetrahydrofuran; hexane / -20 °C

7.1: 2.44 g / Bu₃P; HCO₂NH₄ / Pd(PPh₃)4 / toluene / 1 h / 70 °C

8.1: 97 percent / DDQ; H₂O / CH₂Cl₂ / 0.5 h / 20 °C

9.1: 80 percent / TiCl₄ / CH₂Cl₂; hexane / 0.25 h / -15 °C

10.1: 91 percent / H₂ / Rh[(nbd)dppb]BF₄ / CH₂Cl₂ / 2 h / 20 °C / 7500.75 Torr

11.1: 100 percent / PPTS / CH₂Cl₂ / 2 h / 20 °C

12.1: 96 percent / TBAF / tetrahydrofuran / 3 h / 0 °C

13.1: 89 percent / TPAP; 4 Angstroem molecular sieves; NMO / CH₂Cl₂ / 0.5 h / 20 °C

14.1: 92 percent / SmI₂ / tetrahydrofuran / 0.33 h / -78 °C

15.1: 2,6-lutidine / CH₂Cl₂ / 0.5 h / 0 °C

16.1: 347 mg / LiOH; aq. H₂O₂ / tetrahydrofuran / 3 h / 0 °C

17.1: Et₃N / benzene / 1 h / 20 °C

18.1: 452 mg / Et₃N; DMAP / benzene / 2 h / 20 °C

19.1: 96 percent / PPTS / ethanol / 16 h / 50 °C

20.1: TPAP; NMO; 4 Angstroem molecular sieves / CH₂Cl₂ / 1.5 h / 20 °C

21.1: SmI₂ / tetrahydrofuran / 1 h / -78 °C

21.2: Dess-Martin periodinane / CH₂Cl₂ / 0.5 h / 20 °C

22.1: DMAP / pentane / 168 h / 20 °C

22.2: 31.2 mg / NaBH₄; CeCl₃*7H₂O / methanol / 0.5 h / 0 °C

23.1: 85 percent / 2,6-lutidine / CH₂Cl₂ / 0.5 h / 0 °C

24.1: 85 percent / NaBH₄ / Pd(PPh₃)4 / methanol / 0.5 h / 0 °C

25.1: 69 percent / NH₃; Et₃N; BOP / dioxane; tetrahydrofuran / 48 h / 23 °C

26.1: 31 percent / 2-chloro-1,3-dimethylimidazolinium chloride / CH₂Cl₂ / 1.5 h / 20 °C

27.1: 73 percent / K₂CO₃; MeOH / 1.5 h / 20 °C

28.1: Dess-Martin periodinane / CH₂Cl₂ / 0.5 h / 20 °C

29.1: 8.50 mg / NaBH₄; CeCl₃*7H₂O / methanol / 0.08 h / 0 °C

30.1: 75 percent / 2,6-lutidine / CH₂Cl₂ / 1 h / 0 °C

31.1: 90 percent / DDQ; H₂O / CH₂Cl₂ / 0.25 h / 0 °C

32.1: Dess-Martin periodinane / CH₂Cl₂ / 0.5 h / 20 °C

33.1: NaClO₂; NaH₂PO₄*2H₂O; 2-methyl-2-butene / 2-methyl-propan-2-ol; H₂O / 0.5 h / 20 °C

34.1: 5.20 mg / HF*pyridine; pyridine / tetrahydrofuran / 48 h / 20 °C

With pyridine; 1H-imidazole; 2,6-dimethylpyridine; methanol; dmap; lithium hydroxide; sodium chlorite; sodium tetrahydroborate; sodium dihydrogenphosphate; n-butyllithium; N-methyl-2-indolinone; samarium diiodide; cerium(III) chloride; tetrapropylammonium perruthennate; 2-methyl-but-2-ene; ethanol; tributylphosphine; 4 A molecular sieve; tetrabutyl ammonium fluoride; ammonia; water; hydrogen; dihydrogen peroxide; ammonium formate; pyridinium p-toluenesulfonate; titanium tetrachloride; 2-chloro-1,3-dimethylimidazolinium chloride; potassium carbonate; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; Dess-Martin periodane; pyridine hydrogenfluoride; triethylamine; 2,3-dicyano-5,6-dichloro-p-benzoquinone; tetrakis(triphenylphosphine) palladium⁽⁰⁾; {(1,4-bis(diphenylphosphino)butane)Rh(norbornadiene)}BF₄; In tetrahydrofuran; 1,4-dioxane; methanol; ethanol; hexane; dichloromethane; water; N,N-dimethyl-formamide; toluene; tert-butyl alcohol; pentane; benzene; 21.2: Dess-Martin oxidation / 28.1: Dess-Martin oxidation / 32.1: Dess-Martin oxidation;

DOI:10.1021/jo062089i

upstream raw materials:

(1'R,1S,2S,2'R,8R,9S,11R,13S,15S,16S)-2-(7-cyano-8,16-dihydroxy-9,11,13,15-tetramethyl-18-oxo-oxacyclooctadeca-4,6-dien-2-yl)-cyclopentane-1'-carboxylic acid 2-trimethylsilanyl-ethyl ester

(1R,2R)-2-((4E,6Z)-(2S,9S,11R,13S,15S,16S)-7-Cyano-16-hydroxy-9,11,13,15-tetramethyl-8,18-dioxo-oxacyclooctadeca-4,6-dien-2-yl)-cyclopentanecarboxylic acid

(2S,4R,8S,Z)-9-(tert-butyldiphenylsilyloxy)-2,4,6,8-tetramethylnon-3-en-1-ol

C₄₂H₆₆O₆SiNCOCF₃

Downstream raw materials:

C₃₈H₅₂N₄O₆S

C₃₈H₅₀N₄O₈

C₃₅H₄₉NO₆

C₃₇H₅₂N₂O₈

Refernces

• 1、 Nagamitsu, Tohru,Takano, Daisuke,Fukuda, Takeo,Otoguro, Kazuhiko,Kuwajima, Isao,Harigaya, Yoshihiro,Omura, Satoshi. "Total synthesis of (-)-borrelidin". . p. 1865 - 1867. Retrieved 2007/10/03.
• 2、 Hanessian, Stephen,Yang, Yang,Giroux, Simon,Mascitti, Vincent,Ma, Jianguo,Raeppel, Franck. "Application of Conformation Design in Acyclic Stereoselection: Total Synthesis of Borrelidin as the Crystalline Benzene Solvate". . p. 13784 - 13792. Retrieved 2007/10/03.