Gram‐Scale Preparation of a <i>p</i>‐(C‐Glucopyranosyl)‐<scp>L</scp>‐phenylalanine Derivative by a Negishi Cross‐Coupling Reaction

Ousmer, Malika; Boucard, Valérie; Lubin‐Germain, Nadège; Uziel, Jacques; Augé, Jacques

doi:10.1002/ejoc.200500690

Cited by 23 publications

(30 citation statements)

References 22 publications

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“…For the planned coupling reactions, L ‐phenylalanine was converted to 4‐iodo‐phenylalanine,29 before the tert ‐butyloxycarbonyl (Boc) group and the tert ‐butyl ester30 were introduced to form 21 (Scheme ). Boc‐protected L ‐serine and L ‐threonine also were transformed to their tert ‐butyl esters by treatment with a solution of tert ‐butanol, cylcohexylcarbodiimide and cat.…”

Section: Resultsmentioning

confidence: 99%

C‐Glycosyl Amino Acids through Hydroboration–Cross‐Coupling of exo‐Glycals and Their Application in Automated Solid‐Phase Synthesis

Koch

Schollmeyer

Löwe

et al. 2013

Chemistry A European J

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O-Glycosylation is one of the most important post-translational modifications of proteins. The attachment of carbohydrates to the peptide backbone influences the conformation as well as the solubility of the conjugates and can even be essential for binding to specific ligands in cell-cell interactions or for active transport over membranes. This makes glycopeptides an interesting class of compounds for medical applications. To enhance the long-term availability of these molecules in vivo, the stabilization of the glycosidic bond between the amino acid residue and the carbohydrate is of interest. The described modular approach affords β-linked C-glycosyl amino acids by a sequence of Petasis olefination of glyconolactones, stereoselective hydroboration and a mild B-alkyl-Suzuki coupling reaction. The coupling products were transformed to C-glycosyl amino acid building-blocks suitable for solid-phase synthesis and successfully incorporated into a partial sequence of the tumor-associated MUC1-glycopeptide. The resulting C-glycopeptides are candidates for the development of long-term stable mimics of O-glycopeptide vaccines.

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Section: Resultsmentioning

confidence: 99%

C‐Glycosyl Amino Acids through Hydroboration–Cross‐Coupling of exo‐Glycals and Their Application in Automated Solid‐Phase Synthesis

Koch

Schollmeyer

Löwe

et al. 2013

Chemistry A European J

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“…This precursor ( 3 ) was synthesized from commercially available N -Boc phenylalanine by first converting it to the tert -butyl ester ( 2 ) following a reported procedure (Ousmer M et al, 2006) in 66% yield. The ester 2 was stannylated using Stille reaction to render 3 in 86% yields.…”

Section: Resultsmentioning

confidence: 99%

An alternative and expedient synthesis of radioiodinated 4-iodophenylalanine

Vaidyanathan

McDougald

Grasfeder

et al. 2011

Applied Radiation and Isotopes

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Radiolabeled amino acids have been used extensively in oncology both as diagnostic and therapeutic agents. In our pursuit to develop radiopharmaceuticals to target breast cancer, we were interested in determining the uptake of radioiodinated 4-iodophenylalanine, among other labeled amino acids, in breast cancer cells. In this work, we have developed an alternative method for the synthesis of this agent. The novel tin precursor, (S)-tert-butyl 2-(tert-butoxycarbonylamino)-3-(4-(tributylstannyl)phenyl)propanoate (3) was synthesized from the known, corresponding iodo derivative. Initially, the labeled 4-iodophenylalanine was synthesized from the above tin precursor in two steps with radiochemical yields of 91.6 ± 2.7% and 83.7 ± 1.7% (n = 5), for the radioiodination (first) and deprotection (second) step, respectively. Subsequently, it was synthesized in a single step with an average radiochemical yield of 94.8 ± 3.4% (n = 5). After incubation with MCF-7 breast cancer cells for 60 min, an uptake up to 49.0 ± 0.7% of the input dose was seen; in comparison, the uptake of [14C]phenylalanine under the same conditions was 55.9 ± 0.5%. Furthermore, the uptake of both tracers was inhibited to a similar degree in a concentration-dependent manner by both unlabeled phenylalanine and 4-iodophenylalanine. With [14C]phenylalaine as the tracer, IC50 values of 1.45 mM and 2.50 mM were obtained for Phe and I-Phe, respectively and these values for [125I]I-Phe inhibition were 1.3 and 1.0 mM. In conclusion, an improved and convenient method for the synthesis of no-carrier-added 4-[*I]phenylalanine was developed and the radiotracer prepared by this route demonstrated an amino-acid transporter-mediated uptake in MCF-7 breast cancer cells in vitro that was comparable to that of [14C]phenylalanine.

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“…66 Ousmer et al utilised a Negishi cross-coupling to form a p-(Cglucopyranosyl)phenylalanine derivative (Scheme 17). 67 An iodo-substituted phenylalanine derivative was successfully coupled to a glucal 41 in an excellent 90% yield. This was then further elaborated by stereo-selective hydroboration to yield the desired glucose modified phenylalanine 43 in a 37% overall yield.…”

Section: Synthesis Of Complex Amino Acidsmentioning

confidence: 99%