The DARK Side of Total Synthesis: Strategies and Tactics in Psychoactive Drug Production

• Published in: ACS chemical neuroscience Vol. 9; no. 10; pp. 2307 - 2330
• Main Authors: Chambers, Schuyler A, DeSousa, Jenna M, Huseman, Eric D, Townsend, Steven D
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17.10.2018
• Subjects: Amphetamines - chemical synthesis; Amphetamines - chemistry; Amphetamines - history; Benzodiazepines - chemical synthesis; Benzodiazepines - chemistry; Benzodiazepines - history; Central Nervous System Stimulants - chemical synthesis; Central Nervous System Stimulants - chemistry; Central Nervous System Stimulants - history; Cocaine - chemical synthesis; Cocaine - chemistry; Cocaine - history; Crack Cocaine - chemical synthesis; Crack Cocaine - chemistry; Crack Cocaine - history; Drug Industry; Drug Overdose - epidemiology; Drug Tolerance; Epidemics; Hallucinogens - chemical synthesis; Hallucinogens - chemistry; Hallucinogens - history; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans; N-Methyl-3,4-methylenedioxyamphetamine - chemical synthesis; N-Methyl-3,4-methylenedioxyamphetamine - chemistry; N-Methyl-3,4-methylenedioxyamphetamine - history; Opiate Alkaloids - chemical synthesis; Opiate Alkaloids - chemistry; Opiate Alkaloids - history; Opium - history; Oxycodone - chemical synthesis; Oxycodone - chemistry; Oxycodone - history; Psychotropic Drugs - chemical synthesis; Psychotropic Drugs - chemistry; Psychotropic Drugs - history; Substance-Related Disorders - epidemiology; Synthetic Drugs - chemical synthesis; Synthetic Drugs - chemistry; Synthetic Drugs - history; United States - epidemiology; United States; Opiate; hallucinogens; stimulant; benzodiazepines; psychoactive; opioid
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/acschemneuro.7b00528

Humankind has used and abused psychoactive drugs for millennia. Formally, a psychoactive drug is any agent that alters cognition and mood. The term “psychotropic drug” is neutral and describes the entire class of substrates, licit and illicit, of interest to governmental drug policy. While these drugs are prescribed for issues ranging from pain management to anxiety, they are also used recreationally. In fact, the current opioid epidemic is the deadliest drug crisis in American history. While the topic is highly politicized with racial, gender, and socioeconomic elements, there is no denying the toll drug mis- and overuse is taking on this country. Overdose, fueled by opioids, is the leading cause of death for Americans under 50 years of age, killing ca. 64,000 people in 2016. From a chemistry standpoint, the question is in what ways, if any, did organic chemists contribute to this problem? In this targeted review, we provide brief historical accounts of the main classes of psychoactive drugs and discuss several foundational total syntheses that ultimately provide the groundwork for producing these molecules in academic, industrial, and clandestine settings.