Chemoenzymatic Synthesis of Stannylated Metomidate as a Precursor for Electrophilic Radiohalogenations — Regioselective Alkylation of Methyl 1H‐Imidazole‐5‐carboxylate.

Abstract

Imidazole derivatives R 0190Chemoenzymatic Synthesis of Stannylated Metomidate as a Precursor for Electrophilic Radiohalogenations -Regioselective Alkylation of Methyl 1H-Imidazole-5-carboxylate. -A facile synthesis of the title compound (VIII) via regioselective alkylation of imidazole (V) with chiral 1-(p-iodophenyl)ethanol, obtained via a chemoenzymatic approach, under Mitsunobu reaction conditions is described. -(HAMMERSCHMIDT*, F.; SIMOV, B. P.; SCHMIDT, S.; SCHNEIDER, S.; ZOLLE, I.; Monatsh. Chem. 136 (2005) 2, 229-239; Inst. Org. Chem., Univ. Wien, A-1090 Wien, Austria; Eng.) -D. Singer 22-118

[123I]Iodometomidate for Molecular Imaging of Adrenocortical Cytochrome P450 Family 11B Enzymes

“…Synthesis of IMTO was performed as previously described (16). For synthesis of FETO, MTO [(R)-(ϩ)-methyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate] (3.0 g, 13.0 mmol) was hydrolyzed for 10 min in 30 ml refluxing 10% NaOH.…”

[3H]Metyrapol and 4-[131I]Iodometomidate Label Overlapping, but Not Identical, Binding Sites on Rat Adrenal Membranes

“…The ( R )-Mosher esters of (±)- and ( S )-alcohol were prepared and investigated by 1 H NMR spectroscopy; significant signals of ( R )-Mosher ester of ( R )-alcohol [δ 3.44 (q, J = 1.2, 3H, OCH 3 ), 1.55 (d, J = 6.5, 3H, CH 3 )] and of ( S )-alcohol [3.54 (q, J = 1.2, 3H, OCH 3 ), 1.60 (d, J = 6.5, 3H, CH 3 )]. ( S )-Alcohol (0.167 g, 1.19 mmol, ee >99%) was transformed into ( R )- 24 (0.165 g, 56%) as a colorless oil by a literature procedure (−30 °C to rt in 7 h) except that flash chromatography was performed with hexanes/Et 2 O/ i Pr 2 NH, 6/6/1, R f = 0.31; ee ≥98% [by analytical HPLC on Chiracel OD-H, 1 mL/min, i PrOH/hexanes, 7.5/92.5; ( R )- 24 : t R 14.2 min, ( S )- 24 : t R 12.0 min]; [α] D 20 +71.92 ( c 1.3, acetone). Similarly, (±)- 24 was prepared in 60% yield from racemic alcohol.…”

“…After cooling, the solvents were removed on a rotary evaporator. The residue was flash chromatographed (EtOAc, N -substituted imidazole, R f = 0.26; N -methyl amide, R f = 0.13) to give as a side product the N -methyl amide 30 (7 mg, 19%) as a gum, and the desired N -substituted imidazole 33 (18 mg, 65%) as a liquid: [α] D 20 = −5.95 ( c 1.66, acetone); [α] D 20 −4.62 ( c 1.45, CHCl 3 ) lit . [α] D 20 +5.20 ( c 3.84, CHCl 3 ) for ( S )-(+)-enantiomer.…”

“…Metomidate ( 14 ) was commercially available; the syntheses of its derivatives 15 – 23 (see Table ) have been described; , only the fluoro derivative 24 was newly prepared for this study by a reported method, starting from ( S )-1-(4-fluorophenyl)ethanol of 99% ee. Etomidate ( 25 ) was obtained commercially; the syntheses of its derivatives 26 – 32 (see Table ) have been described. , During a first attempt to convert 14 in one step to the N -methylamide 30 , unexpectedly the ester group was almost quantitatively lost, opening an easy synthetic access to etomidate analogues without ester group. Consequently, we prepared 33 and 34 from 25 and 20 , respectively (Scheme ).…”

“…The preparation of ( S )- 33 from 1-phenylethylamine has been described . Finally, we tested pyridin-3-yl derivatives of 14 and 16 , ( 36 and 37 ) and the 2,2′-bipyridin-5-yl derivatives 38 – 41 . , …”