Synthesis of fluorine‐18 labeled sulfonureas as β‐cell imaging agents

Tolbutamide ( 1 ) and glyburide ( 7 ) are hypoglycemic drugs used to stimulate insulin secretion in type 2 diabetic patients. We have synthesized their fluorine‐18 labeled analogs, 1‐[(4‐[ 18 F]fluorobenzenesulfonyl)]‐3‐butyl]urea ( p ‐[ 18 F]fluorotolbutamide, 3a ) and N‐{4‐[β‐(2‐[ 18 F]fluoroethoxybenzene carboxamido)ethyl]benzenesulfonyl}‐N′‐cyclohexylurea (2‐[ 18 F]fluoroethoxyglyburide, 6a ) as β‐cell imaging agents. Compound 3a was synthesized via two approaches: One‐step synthesis via nucleophilic substitution of p ‐nitrotolbutamide ( 2 ) with K[ 18 F]/Kryptofix 2.2.2 in either CH 3 CN or DMSO gave a complicated mixture; a two‐step synthesis via preparation and reaction of 4‐[ 18 F]fluorobenzenesulfonamide with butyl isocyanate in the presence of either copper (I) chloride or borontrifluoride etherate complex in CH 3 CN followed by HPLC purification yielded compound 3a in an overall yield of 1–2% with a synthesis time of 120 minutes from EOB. Compound 6a was synthesized by alkylation of the corresponding hydroxy precursor ( 5 ) with [ 18 F]fluoroethyl tosylate in DMSO at 120°C for 20 minutes followed by HPLC purification in an overall yield of 5–10 % with a synthesis time of 100 minutes from Copyright © 2001 John Wiley & Sons, Ltd.