R. NORLIN*, G. LINDBERG (SWEDISH DEFENSE RESEARCH AGENCY, NBC-PROTECTION Category DIVISION, UMEÅ, SWEDEN) Chemistry in Synthesis of [14C] Sarin Medicine and J. Label. Compd. Radiopharm. 2003, 46, 599–604, DOI: 10.1002/jlcr.699. Biology Sarin and Other G-Series Nerve Agents Key words sarin nerve agents Sarin and other G-series nerve agents: O chemical weapons O O O P P P N O P O O O F F F N sarin soman tabun cyclosarin 3 3 3 3 LCt50: 35 mg-min/m LCt50: 35 mg-min/m LCt50: 70 mg-min/m LCt50: 35 mg-min/m Synthesis of 14C-labeled sarin: oxalyl chloride 14 O O O [ C]MeI 1 mM HCl Et3N, CDCl3 P(OEt)3 P OEt P OH P Cl 93% yield 97% yield 90% yield OEt OH Cl O O HF HO P P F Et N O F 3 F 75% yield over 2 steps (±) [14C] sarin Mechanism of action: Ser 200 Ser 200 O O – H+ O H P O P O O F F – F– Sarin Ser 200 Ser 200 O dealkylation O P O P O O O irreversible enzyme inhibitor Significance: Sarin and the other G-series nerve Comment: Norlin and Lindberg report the synthe- agents were initially discovered between 1936 and sis of 14C-labeled sarin in five steps. Triethyl phos- 1949 by German scientists led by Gerhard Schrader phite is reacted with [14C] MeI and the correspond- while initially researching insecticides. As a nerve ing phosphonate is hydrolyzed and chlorinated. The agent, sarin inhibits acetylcholinesterase (AChE) resulting phosphonic acid dichloride was fluorinat- from breaking down acetylcholine (Ach) and allows ed with hydrogen fluoride (HF) and immediately re- for its build-up in the synaptic cleft, causing nerve acted with isopropanol and triethylamine to yield impulses to be constantly transmitted. Exposure to [14C] sarin as a racemic mixture in 61% overall yield. sarin leads to paralysis and eventually death by suf- This method is unsuited for synthesis in conven- focation if not swiftly treated. While not deployed tional labs due to the corrosive and dangerous na- in World War II, sarin was used in several recent ture of HF. tragedies such as the Tokyo subway chemical at- tack by the Aum Shinrikyo cult in 1995. SYNFACTS Contributors: Dirk Trauner, Tongil Ko Synfacts 05012021, 17(01), 0101 Published online: 16.12.20201861-19581861-194X DOI: 10.1055/s-0040-1719251; Reg-No.: T14320SF Georg Thieme Verlag KG Rüdigerstaße 14, 70469 Stutgart © 2021. Thieme. All rights reserved. 101 Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany.