ChemInform Abstract: SYNTHESIS OF (15N)‐, (1‐13C)‐, (3‐13C)‐, (RING‐1,2‐13C2)‐, AND (RING‐3,4,5‐13C3)‐LABELED DL‐TYROSINE

Abstract

Die für biochemische Experimente als Substrate erforderlichen, markierten Tyrosine (I) werden ‐ wie im Formelschema skizziert ‐ synthetisiert.

Synthetic approaches to regiospecifically mono‐ and dilabelled arenes

“…Although this approach has not been widely used for the preparation of labelled arenes, many unlabelled examples have been reported, along with two further examples where the dienophile is labelled as methyl propiolate. Cycloaddition in these cases requires elevated temperatures when 3‐hydroxy‐2‐pyranone is used as the dienophile (Scheme ),127 but the normal demand cycloaddition with Danishefsky's diene proceeds efficiently under very much milder conditions (Scheme) 128. Propiolic acid is commercially available in both 13 C and 14 C labelled forms, providing a comparatively simple access into specifically substituted point‐labelled arenes.…”

A Convenient Synthesis of 4-Hydroxy[1-13C]benzoic Acid and Related Ring-Labelled Phenolic Compounds

“…Heating of 13 in hydrobromic acid furnished D,L-[1′-13 C]tyrosine (14) in 42% overall yield. 15 In order to obtain ring-labelled 1,2,4-trihydroxy [4][5][6][7][8][9][10][11][12][13] C]benzene (19) we developed a reaction sequence starting from 3,4-dihydroxy[1-13 C]benzoic acid (9) (Scheme 4). Treatment of this compound with methyl iodide and K 2 CO 3 in acetone afforded methyl 3,4-dimethoxy-[1-13 C]benzoate (15) in 88% yield.…”

“…6 As part of an ongoing project concerning the biosynthesis of boviquinones and related meroterpenoids from mushrooms 7 we needed specifically 13 C ring-labelled 4-hydroxybenzoic acid, 3,4-dihydroxy-benzoic acid, tyrosine and 1,2,4trihydroxybenzene for feeding experiments. Previous work in this field includes syntheses of 4-hydroxy [1,[2][3][4][5][6][7][8][9][10][11][12][13] C 2 ]benzoic acid and [1,2-13 C 2 ]tyrosine from 13 C-labelled ethylene, 8 the synthesis of [3,[5][6][7][8][9][10][11][12][13] C 2 ]-9 and [3,4,5-13 C 3 ]tyrosine 5 from 13 C-labelled acetone and the preparation of 1,2,4-trihydroxy[1,4-13 C 2 ]benzene 10 from Na 13 CN. These syntheses, however, require many steps and afford the labelled compounds only in moderate overall yields.…”

Synthesis of 13C‐labeled parabens from isotopically enriched phenols using the Houben–Hoesch reaction

“…Unfortunately, there are relatively few methods for the selective synthesis of 13 C‐labeled phenol derivatives. Those that have been reported usually involve the de novo synthesis of the aromatic ring through condensation reactions, 12–14 the Diels–Alder reaction, 15 the dehydrogenation of cyclohexanones, 16 or the microbial biotransformation of 13 C‐labeled glucose 17 …”

“…Unfortunately, there are relatively few methods for the selective synthesis of 13 C-labeled phenol derivatives. Those that have been reported usually involve the de novo synthesis of the aromatic ring through condensation reactions, [12][13][14] the Diels-Alder reaction, 15 the dehydrogenation of cyclohexanones, 16 or the microbial biotransformation of 13 C-labeled glucose. 17 By far, the most general method for the synthesis of 13 C-labeled parabens (and related 4-substituted phenols) is the condensation of the heterocycle 4H-pyran-4-one with ethyl acetoacetate, as originally reported by Steglich in 1998 (Scheme 1A).…”