omega-1-Hydroxy Fentanyl
[CAS# 99624-68-7]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: omega-1-Hydroxy Fentanyl
• Synonyms: 2-hydroxy-N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide
• Molecular Formula: C₂₂H₂₈N₂O₂
• Molecular Weight: 352.47
• CAS Registry Number: 99624-68-7
• SMILES: CC(C(=O)N(C1CCN(CC1)CCC2=CC=CC=C2)C3=CC=CC=C3)O

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 497.1±45.0 ºC 760 mmHg (Calc.)^*
• Flash point: 254.4±28.7 ºC (Calc.)^*
• Index of refraction: 1.6 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

ω-1-Hydroxy fentanyl is a synthetic opioid and a structural analog of fentanyl, characterized by the presence of a hydroxyl group on the terminal carbon of the propionamide side chain. This modification involves hydroxylation at the ω-1 (penultimate) position of the alkyl chain, introducing a polar functional group that can affect both the pharmacokinetic and pharmacodynamic properties of the molecule.

The introduction of a hydroxyl group into the lipophilic side chain alters the compound’s solubility and metabolism. Hydroxylated fentanyl derivatives are known to exhibit changes in receptor binding affinity, metabolic stability, and duration of action. In the case of ω-1-hydroxy fentanyl, the hydroxyl group may enhance hydrogen bonding interactions or alter the conformation of the molecule when bound to the μ-opioid receptor, although the compound is still presumed to act as a full agonist at this receptor site. Its potency relative to fentanyl is not well established in the literature, but it is likely to remain a highly active opioid due to the conserved piperidine and anilide pharmacophore.

The hydroxyl group can also be a site for phase II metabolism, such as glucuronidation or sulfation, which may accelerate elimination from the body compared to non-hydroxylated analogs. However, it may also confer metabolic stability depending on the overall structure and substitution pattern. As with other fentanyl analogs, ω-1-hydroxy fentanyl is not approved for medical use and has emerged in the context of synthetic opioid development and forensic toxicology.

This compound may appear as a byproduct or impurity in illicit fentanyl production or as a designer drug intended to circumvent controlled substance regulations. The presence of hydroxylated fentanyl analogs in biological specimens has been documented in postmortem toxicology and overdose investigations, often in combination with other synthetic opioids. The compound’s effects—profound analgesia, sedation, euphoria, respiratory depression, and potential lethality—are consistent with the opioid class.

Detection and identification of ω-1-hydroxy fentanyl in forensic settings require advanced analytical techniques due to its structural similarity to other fentanyl analogs. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) or high-resolution mass spectrometry (HRMS) is typically employed for reliable quantification and structural elucidation. Immunoassays may not reliably detect the compound unless specifically calibrated, underscoring the need for targeted screening.

Regulatory responses to fentanyl analogs such as ω-1-hydroxy fentanyl have focused on broad scheduling of structural classes to prevent circumvention through minor chemical modifications. This approach seeks to stem the tide of new derivatives entering the illicit drug market, although new analogs continue to be reported. The addition of functional groups like hydroxyls is a common strategy in clandestine synthesis, offering subtle chemical alterations that retain or enhance pharmacological activity while potentially evading existing legal definitions.

As with all potent synthetic opioids, the primary clinical concern with ω-1-hydroxy fentanyl is respiratory depression, which can be rapid and severe. Naloxone remains the standard treatment for opioid overdose, though higher doses or repeated administration may be necessary due to the high receptor affinity and potency of fentanyl analogs. The continued appearance of such compounds highlights the dynamic nature of opioid synthesis and the need for vigilant forensic, clinical, and public health surveillance.

References

2019. Affinity of fentanyl and its derivatives for the s1-receptor. MedChemComm, 10(7).
DOI: 10.1039/c9md00222g
PMID: 31391893
PMCID: PMC6657672