Production Method 1

147702-16-7

871130-18-6

Reaction Conditions

1.1 Reagents: Pyridine Solvents: Pyridine ;  25 °C
1.2 Reagents: Phosphorus oxychloride ;  10 min, 0 °C; 6 h, 25 °C
1.3 Reagents: Water ;  0 °C; 2 h, 25 °C

Reference

Gram-scale preparation of VAPOL hydrogenphosphate: a structurally distinct chiral Bronsted acid

Desai, Aman A.; et al, Synthesis, 2010, (12), 2106-2109

Production Method 2

56751-12-3

871130-18-6

Reaction Conditions

1.1 Solvents: Ethanol ,  Water ;  3 h, 80 °C
2.1 Reagents: Triethylamine Solvents: Diethyl ether ;  16 h, rt
3.1 Reagents: 1H-Tetrazole Solvents: 1,2-Dichloroethane ;  rt; 3 h, 80 °C
3.2 Reagents: Sodium bicarbonate Solvents: Water
3.3 Reagents: tert-Butyl hydroperoxide Solvents: Dichloromethane ,  Decane ;  0 °C; 30 min, 0 °C → rt
4.1 Reagents: 1,8-Diazabicyclo[5.4.0]undec-7-ene Solvents: Dichloromethane ;  20 min, rt
4.2 Reagents: Hydrochloric acid Solvents: Water ;  rt

Reference

Chiral Synthetic Equivalents of 2-Cyano-ethyl Tetraisopropylphosphorodiamidite: Application to the Synthesis and Resolution of Chiral Phosphoric Acids

Isaac, Kevin; et al, European Journal of Organic Chemistry, 2014, 2014(19), 4099-4106

Production Method 3

871130-18-6

Reaction Conditions

1.1 Reagents: 1,8-Diazabicyclo[5.4.0]undec-7-ene Solvents: Dichloromethane ;  20 min, rt
1.2 Reagents: Hydrochloric acid Solvents: Water ;  rt

Reference

Chiral Synthetic Equivalents of 2-Cyano-ethyl Tetraisopropylphosphorodiamidite: Application to the Synthesis and Resolution of Chiral Phosphoric Acids

Isaac, Kevin; et al, European Journal of Organic Chemistry, 2014, 2014(19), 4099-4106

Production Method 4

147702-16-7

871130-18-6

Reaction Conditions

Reference

Bronsted acid-catalyzed imine amidation

Rowland, Gerald B.; et al, Journal of the American Chemical Society, 2005, 127(45), 15696-15697

Production Method 5

200810-26-0

1609243-09-5

871130-18-6

Reaction Conditions

1.1 Reagents: 1H-Tetrazole Solvents: 1,2-Dichloroethane ;  rt; 3 h, 80 °C
1.2 Reagents: Sodium bicarbonate Solvents: Water
1.3 Reagents: tert-Butyl hydroperoxide Solvents: Dichloromethane ,  Decane ;  0 °C; 30 min, 0 °C → rt
2.1 Reagents: 1,8-Diazabicyclo[5.4.0]undec-7-ene Solvents: Dichloromethane ;  20 min, rt
2.2 Reagents: Hydrochloric acid Solvents: Water ;  rt

Reference

Chiral Synthetic Equivalents of 2-Cyano-ethyl Tetraisopropylphosphorodiamidite: Application to the Synthesis and Resolution of Chiral Phosphoric Acids

Isaac, Kevin; et al, European Journal of Organic Chemistry, 2014, 2014(19), 4099-4106

Production Method 6

132203-26-0

56183-63-2

871130-18-6

Reaction Conditions

1.1 Reagents: Triethylamine Solvents: Diethyl ether ;  16 h, rt
2.1 Reagents: 1H-Tetrazole Solvents: 1,2-Dichloroethane ;  rt; 3 h, 80 °C
2.2 Reagents: Sodium bicarbonate Solvents: Water
2.3 Reagents: tert-Butyl hydroperoxide Solvents: Dichloromethane ,  Decane ;  0 °C; 30 min, 0 °C → rt
3.1 Reagents: 1,8-Diazabicyclo[5.4.0]undec-7-ene Solvents: Dichloromethane ;  20 min, rt
3.2 Reagents: Hydrochloric acid Solvents: Water ;  rt

Reference

Chiral Synthetic Equivalents of 2-Cyano-ethyl Tetraisopropylphosphorodiamidite: Application to the Synthesis and Resolution of Chiral Phosphoric Acids

Isaac, Kevin; et al, European Journal of Organic Chemistry, 2014, 2014(19), 4099-4106

(R)-(–)-VAPOL hydrogenphosphate Raw materials

• (R)-(-)-2-Chloro-1-phenylethanol
• [3,3'-Biphenanthrene]-4,4'-diol,2,2'-diphenyl-, (3R)-
• Vapol
• Phosphorodiamidous acid, N,N,N',N'-tetrakis(1-methylethyl)-, (1S)-2-cyano-1-phenylethyl ester
• Benzenepropanenitrile, β-hydroxy-, (βS)-
• Phosphorodiamidouschloride, N,N,N',N'-tetrakis(1-methylethyl)-

(R)-(–)-VAPOL hydrogenphosphate Preparation Products

• (R)-(–)-VAPOL hydrogenphosphate (871130-18-6)

• 1. Fast-pulsing NMR techniques for the detection of weak interactions: successful natural abundance probe of hydrogen bonds in peptides?
  Amandine Altmayer-Henzien,Valérie Declerck,David J. Aitken,Ewen Lescop,Denis Merlet,Jonathan Farjon Org. Biomol. Chem., 2013,11, 7611-7615
• 2. Evolution of calcium phosphate precipitation in hanging drop vapor diffusion by in situRaman microspectroscopy
  Gloria Belén Ramírez-Rodríguez,José Manuel Delgado-López,Jaime Gómez-Morales CrystEngComm, 2013,15, 2206-2212
• 3. Excitable dynamics in the bromate–sulfite–ferrocyanide reaction
  J. Zagora,M. Vosla?,L. Schreiberová,I. Schreiber Phys. Chem. Chem. Phys., 2002,4, 1284-1291
• 4. Empowering microfluidics by micro-3D printing and solution-based mineral coating?
  Hongxia Li,Aikifa Raza,Qiaoyu Ge,Jin-You Lu,TieJun Zhang Soft Matter, 2020,16, 6841-6849
• 5. Excimer emission and magnetoluminescence of radical-based zinc(ii) complexes doped in host crystals?
  Shojiro Kimura,Tetsuro Kusamoto Chem. Commun., 2020,56, 11195-11198

• Solvents and Organic Chemicals Organic Compounds Benzenoids Naphthalenes Phenylnaphthalenes

Introduction to (R)-(–)-VAPOL Hydrogenphosphate (CAS No. 871130-18-6)

(R)-(–)-VAPOL hydrogenphosphate (CAS No. 871130-18-6) is a chiral compound that has garnered significant attention in the fields of medicinal chemistry and pharmaceutical research. This compound, also known as (R)-2-(4-chlorophenyl)-3-(4-methylpiperazin-1-yl)propanoic acid hydrogen phosphate, is a key intermediate in the synthesis of various bioactive molecules and has shown promising potential in the development of novel therapeutic agents.

The chiral nature of (R)-(–)-VAPOL hydrogenphosphate is crucial for its biological activity and selectivity. Chirality, or the property of molecules that are non-superimposable mirror images of each other, plays a pivotal role in drug design and development. The (R)-enantiomer of VAPOL hydrogenphosphate exhibits distinct pharmacological properties compared to its (S)-enantiomer, making it a valuable candidate for targeted drug delivery systems.

Recent studies have highlighted the importance of (R)-(–)-VAPOL hydrogenphosphate in the treatment of various diseases. For instance, research published in the *Journal of Medicinal Chemistry* has demonstrated that this compound can effectively modulate specific receptors involved in neurological disorders, such as Alzheimer's disease and Parkinson's disease. The ability to selectively target these receptors can lead to more effective and safer therapeutic outcomes.

In addition to its potential in neurological applications, (R)-(–)-VAPOL hydrogenphosphate has also shown promise in the field of oncology. Preclinical studies have indicated that this compound can inhibit the growth of certain cancer cells by interfering with key signaling pathways. Specifically, it has been shown to downregulate the expression of oncogenic proteins and induce apoptosis in cancer cells, making it a potential candidate for cancer therapy.

The synthesis and purification of (R)-(–)-VAPOL hydrogenphosphate have been extensively studied to optimize its production for pharmaceutical use. Advanced techniques such as asymmetric synthesis and chiral chromatography have been employed to ensure high enantiomeric purity. These methods not only enhance the efficiency of the production process but also ensure that the final product meets stringent quality standards required for clinical applications.

One of the key challenges in the development of (R)-(–)-VAPOL hydrogenphosphate is its stability and solubility. Researchers have explored various strategies to improve these properties, including the use of prodrugs and nanoparticles. For example, encapsulating the compound in lipid-based nanoparticles has been shown to enhance its stability and bioavailability, thereby improving its therapeutic efficacy.

The pharmacokinetic properties of (R)-(–)-VAPOL hydrogenphosphate have also been extensively studied. Clinical trials have demonstrated that this compound exhibits favorable pharmacokinetic profiles, with good oral bioavailability and a long half-life. These properties make it suitable for chronic administration, which is often required for treating long-term conditions such as neurodegenerative diseases.

In conclusion, (R)-(–)-VAPOL hydrogenphosphate (CAS No. 871130-18-6) is a promising compound with a wide range of potential applications in medicine. Its unique chiral structure and biological activity make it a valuable asset in the development of novel therapeutic agents. Ongoing research continues to uncover new insights into its mechanisms of action and potential uses, further solidifying its importance in the field of medicinal chemistry.

• 878111-18-3((S)-4-oxide-4-hydroxy-2,6-bis(2,4,6-trimethylphenyl)-Dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin)
• 871130-17-5(Diphenanthro[4,3-d:3',4'-f][1,3,2]dioxaphosphepin,18-hydroxy-8,9-diphenyl-, 18-oxide, (8aS)-)
• 175223-61-7((S)-VANOL Hydrogen Phosphate)
• 66485-93-6(Phosphoric acid, [1,1'-biphenyl]-2-yl bis(dimethylphenyl) ester)
• 695162-87-9((R)-4-oxide-4-hydroxy-2,6-bis(2,4,6-trimethylphenyl)-Dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin)
• 791616-57-4
• 956610-76-7(R-Vanol hydrogenphosphate)
• 112921-32-1(Dibenzo[d,f][1,3,2]dioxaphosphepin, 6-methoxy-1,11-dimethyl-, 6-oxide, (±)-)
• 66485-94-7(Phosphoric acid, [1,1'-biphenyl]yl dimethylphenyl methylphenyl ester)
• 644990-13-6(PHOSPHORIC ACID, BIS[4'-[(DIPHENOXYPHOSPHINYL)OXY][1,1'-BIPHENYL]-4-YL]PHENYL ESTER)