Tetrahydropiperine
[CAS# 23434-88-0]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs
• Name: Tetrahydropiperine
• Synonyms: 5-(1,3-Benzodioxol-5-yl)-1-(1-piperidinyl)-1-pentanone; Cosmoperine
• Molecular Formula: C₁₇H₂₃NO₃
• Molecular Weight: 289.37
• CAS Registry Number: 23434-88-0
• SMILES: C1CCN(CC1)C(=O)CCCCC2=CC3=C(C=C2)OCO3

Properties

• Solubility: Practically insoluble (0.025 g/L) (25 °C), Calc.^*
• Density: 1.156±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Index of Refraction: 1.556, Calc.^*
• Boiling Point: 469.9±24.0 °C (760 mmHg), Calc.^*
• Flash Point: 238.0±22.9 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2017 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P280-P301+P312-P302+P352-P305+P351+P338

Discovery and Applications

Tetrahydropiperine is a bioactive alkaloid derivative, structurally characterized as a saturated form of piperine, the major pungent compound found in black pepper (*Piper nigrum*). Its molecular formula, C17H19NO3, represents a modified piperine framework in which the double bonds in the aliphatic chain are fully hydrogenated. The substance has attracted interest for its enhanced bioavailability and pharmacokinetic properties compared to its precursor, piperine.

Tetrahydropiperine was first synthesized as part of research into improving the bioavailability of natural bioactives. The reduction of piperine to tetrahydropiperine, typically achieved through catalytic hydrogenation, results in a compound with improved solubility and stability. This discovery was motivated by the need to enhance the absorption and efficacy of bioactive substances in nutraceutical and pharmaceutical applications.

One of the primary applications of tetrahydropiperine is as a bioavailability enhancer. It has been shown to improve the absorption of various compounds, including curcumin, resveratrol, and vitamins. By modulating gastrointestinal enzymes and transporters, tetrahydropiperine increases the systemic availability of co-administered drugs and nutraceuticals. This property has made it a valuable ingredient in dietary supplements and functional foods aimed at maximizing health benefits.

Tetrahydropiperine also demonstrates potential in cosmetic applications. Its ability to penetrate the skin barrier makes it a suitable carrier for active ingredients in topical formulations. By facilitating deeper delivery of antioxidants, anti-aging agents, and other bioactives, it enhances the effectiveness of skincare products.

The compound’s safety profile has been evaluated in several studies, indicating low toxicity and minimal adverse effects at typical doses. These findings support its use in consumer products, although regulatory approval and compliance vary across regions.

Tetrahydropiperine continues to be explored for additional therapeutic applications, including its potential roles in managing inflammation, metabolic disorders, and drug resistance. Ongoing research aims to expand its utility in diverse fields, leveraging its unique chemical and biological properties.

References

2012. Synthesis and inhibitory effect of piperine derivates on monoamine oxidase. *Bioorganic & Medicinal Chemistry Letters*, 22(9).
DOI: 10.1016/j.bmcl.2012.02.090

2010. In vitro TRPV1 activity of piperine derived amides. *Bioorganic & Medicinal Chemistry*, 18(9).
DOI: 10.1016/j.bmc.2010.03.013

2001. Tetrahydropiperine, the first natural aryl pentanamide from Piper longum. *Biochemical Systematics and Ecology*, 29(5).
DOI: 10.1016/s0305-1978(00)00083-1