Synthesis of Nonproteinogenic (R)‐ or (S)‐Amino Acids Analogues of Phenylalanine, Isotopically Labelled and Cyclic Amino Acids from tert‐Butyl 2‐(tert‐Butyl)‐3‐methyl‐4‐oxo‐1‐imidazolidinecarboxylate (Boc‐BMI)

Abstract

The enantiomerically pure glycine derivatives (R)‐ and (S)‐Boc‐BMI, commercially available on a kg scale, are used as starting materials (Scheme 1) for the preparation of (i) open‐chain amino acids such as α‐deuterio amino acids (4, 5), β‐arylalanines (2), aspartic acid derivatives (6, 7a, 8), or ω‐halo amino acids (7b, c, 12, 13, 16, 17, 19, 22), (ii) of α‐aminocycloalkanecarboxylic acids (9, 11), and (iii) of heterocyclic α‐amino acids (14, 15, 18, 20) containing azetidine, pyrrolidine, piperidine or perhydroazepine rings. Inversion by deprotonation / protonation or deuteration allows to prepare either enantiomer of an amino acid from the same Boc‐BMI enantiomer (Scheme 5). Effects of additives such as the cyclic urea DMPU, lithium salts, or secondary amines upon the reactivity of lithium enolates are discussed and, in part, exploited.

Three-Step, “One-Pot” Radiosynthesis of 6-Fluoro-3,4-Dihydroxy-l-Phenylalanine by Isotopic Exchange

“…NCA 18 F-fluoride was produced by the 18 O(p,n) 18 F nuclear reaction with the BC 1710 cyclotron (Japan Steel Works) at Forschungszentrum Jülich as described earlier (19). The 18 F-fluoride produced was purified through electrostatic adsorption on a Sigradur-Anode (HTW Hochtemperatur-Werkstoffe GmbH) and desorption into 500 mL of pentadistilled water (20).…”

“…Nevertheless, the electrophilic method is limited to the production of small amounts of activity at high costs, even when the 18 O(p,n) 18 F nuclear reaction is used (11), and only half of the radioactivity of molecular 18 F-F 2 can be incorporated. Therefore, the use of this important tracer in clinical centers is limited mainly by the lack of a nucleophilic radiofluorination method based on the advantage of the large-scale production of 18 F-fluoride.…”

“…The first nucleophilic approaches for the radiosynthesis of 6-18 F-fluoro-L-DOPA were based on substitution with 18 F-fluoride on small benzaldehyde derivatives (12). After the 18 F-labeling step, the aldehyde functionality was converted to a benzyl halide group, subsequently coupled either to chiral auxiliaries (13) or to a prochiral auxiliary by chiral phase transfer alkylation (14).…”

“…After the 18 F-labeling step, the aldehyde functionality was converted to a benzyl halide group, subsequently coupled either to chiral auxiliaries (13) or to a prochiral auxiliary by chiral phase transfer alkylation (14). The latter strategy permits the large-scale production of 6-18 F-fluoro-L-DOPA with excellent chemical, radiochemical, and enantiomeric purities (.96%).…”

“…Unfortunately, no 18 F-labeling results with this precursor have been reported so far. It can be presumed that the stability of the precursor is not sufficient for an 18 F-labeling reaction.…”