An efficient, optimized synthesis of fentanyl and related analogs

Carlos A Valdez; Roald N Leif; Brian P Mayer

doi:10.1371/journal.pone.0108250

An efficient, optimized synthesis of fentanyl and related analogs

PLoS One. 2014 Sep 18;9(9):e108250. doi: 10.1371/journal.pone.0108250. eCollection 2014.

Authors

Carlos A Valdez¹, Roald N Leif¹, Brian P Mayer¹

Affiliation

¹ Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California, United States of America; Forensic Science Center, Lawrence Livermore National Laboratory, Livermore, California, United States of America.

Abstract

The alternate and optimized syntheses of the parent opioid fentanyl and its analogs are described. The routes presented exhibit high-yielding transformations leading to these powerful analgesics after optimization studies were carried out for each synthetic step. The general three-step strategy produced a panel of four fentanyls in excellent yields (73-78%) along with their more commonly encountered hydrochloride and citric acid salts. The following strategy offers the opportunity for the gram-scale, efficient production of this interesting class of opioid alkaloids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkylation
Analgesics, Opioid / chemical synthesis*
Fentanyl / analogs & derivatives*
Fentanyl / chemical synthesis*
Oxidation-Reduction

Substances

Analgesics, Opioid
Fentanyl

Grants and funding

The authors (CAV, BPM, and RNL) received funding from Lawrence Livermore National Laboratory (llnl.gov) under the Laboratory Directed Research and Development (LDRD) program, project number 14-ERD-048. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.