Onversion of [18 F]2 to [18 F]1. We hypothesized that, when the 18 Ffluorination step had been performed in an atmosphere absolutely free on the carbonate base, that is ordinarily present in typical [18 F]F incorporation reactions, an efficient and reproducible acidmediated deprotection will be easier to achieve and may permit for the removal of acetonide below milder situations. Herein, we describe an alternative radiosynthesis of [18 F]MCL524 utilizing NAMB [18 F]F incorporation chemistry, also as an unconventional Lewisacidbased strategy for the deprotection of intermediate [18 F]2.Chemistry 2021,2. Materials and Strategies Radiosynthesis of [18 F]MCL524 ([18 F]1) through In(OTf)3 Mediated Deprotection An aliquot of [18 F]F (190 MBq) in [18 O]H2 O was diluted to 2 mL with H2 O and also the was captured on a commercial QMA AEX column (carbonate kind, 102 mg; MedChem Imaging, LLC), which was previously activated with water (1 mL). Just after washing the column with ANGPTL 8 Protein Human anhydrous MeCN (three mL), a continuous flow of Ar was passed by way of the column for 10 min. The [18 F]F was eluted in the column within the reverse path into a microwavable test tube utilizing a one hundred remedy of TEATos (23.7 mg/mL) in 7:three MeCN:H2 O. Residual eluent was ejected in the column applying a syringe filled with air (ten mL). The precursor, MCL556 (3; 1 mg), in anhydrous MeCN (900 ), was added towards the eluate, as well as the tube was crimpsealed, magnetically stirred for 20 s and heated to 150 C in a microwave heater (BiotageInitiator) for 15 min. Immediately after removing compact aliquots for radioTLC (10 EtOH in CH2 Cl2 , silica gel, 49 two radiochemical conversion (RCC), n = four) and analytical HPLC (HPLC 1, Program A within the Supporting Facts), the 18 Ffluorination reaction mixture containing [18 F]2 was added to solid In(OTf) (ten.35 mg) 3 in a microwave test tube. Water was added (100 ), as well as the reaction mixture was heated to 150 C (microwave) for 20 min. The % conversion of intermediate [18 F]2 to [18 F]1 (38 ) was assayed by analytical HPLC (HPLC 1, Plan A). The crude reaction mixture was diluted to two mL with sodium acetate buffer (50 mM AcOH/2.five mM NaOAc) containing 0.1 mg/mL ascorbic acid and purified by preparative HPLC (HPLC two, Program D). The collected solution was diluted with water (50 mL) and trapped on a SepPakC18 Plus cartridge, which was previously activated with three mL of EtOH and ten mL of water. [18 F]MCL524 was eluted from the column with EtOH (1.5 mL) and diluted with 0.9 saline (1.five mL) containing sodium ascorbate (3 mg/mL). The final formulation was passed via a 0.2 filter to afford 7.06 MBq (191 i) of [18 F]MCL524 [3.7 nondecay corrected, 9.2 decay corrected (DC)] in 1:1 EtOH:sodium ascorbate (4.five mg) in isotonic saline (3 mL total). Item identity and molar activity were assessed by HPLC (HPLC 1, Plan C). Total synthesis time was 146 min from startofsynthesis. [18 F]F three. Benefits 3.1. Summary of NonRadioactive Synthesis Tosylated precursor MCL556 (3) [33] was PRKG1 Protein Human synthesized as previously described, with several minor modifications (Scheme 2 and Scheme S1 within the Supporting Facts). Thebaine was Ndemethylated with DIAD [47], and after that alkylated to afford RNnpropylnorthebaine (4) based on the previously published procedure [48]. Intermediate 4 was then Odemethylated by refluxing in 48 HBr in glacial acetic acid to afford R2,10,11trihydroxynpropylnorapomorphine hydrobromide (five; TNPA) [48]. The catechol moiety of five was protected as an acetonide using acetone and phosphorus.