Generation of unnatural α,α-disubstituted amino acid derivatives from cyclic sulfamidates

Boulton, Lee T.; Stock, H. Thijs; Raphy, J.; Horwell, David C.

doi:10.1039/a901667h

Cited by 49 publications

(21 citation statements)

References 22 publications

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“…As an alternative to sulfonate ester precursors, five member cyclic sulfamidates derived from β‐amino alcohols are amenable to nucleophilic substitution at the O ‐substituted position even in compounds with steric hinderance . Preparation of these compounds is typically accomplished by reacting an N ‐alkyl or N ‐protected β‐amino alcohol with thionyl chloride to form a cyclic sulfamidite intermediate, which is then oxidized using sodium periodate with a rhuthenium (IV) catalyst to provide the cyclic sulfamidate.…”

Section: Fluorine‐18 and Radioiodinated αα‐Dialkyl Amino Acidsmentioning

confidence: 99%

“…Preparation of these compounds is typically accomplished by reacting an N ‐alkyl or N ‐protected β‐amino alcohol with thionyl chloride to form a cyclic sulfamidite intermediate, which is then oxidized using sodium periodate with a rhuthenium (IV) catalyst to provide the cyclic sulfamidate. This strategy was used to prepare the nonradioactive N ‐(4‐methoxybenzyl) methyl ester derivative of racemic FAMP from the appropriate cyclic sulfamidate with tetrabutyl ammonium fluoride as the source of nucleophilic fluoride . The initially reported synthesis of racemic FAMP proceeded through a hydantoin intermediate obtained using a modified Bucherer–Strecker reaction to provide the N ‐Boc t ‐butyl ester‐protected α‐methyl‐serine intermediate 62 (Scheme ) .…”

Section: Fluorine‐18 and Radioiodinated αα‐Dialkyl Amino Acidsmentioning

confidence: 99%

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Radiohalogenated nonnatural amino acids as PET and SPECT tumor imaging agents

McConathy

Jarkas

et al. 2011

Medicinal Research Reviews

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Radiohalogenated α-amino acids are a diverse and useful class tumor imaging agents suitable for positron emission tomography and single photon emission computed tomography. These tracers target the increased rates of amino acid transport exhibited by many tumor cells. The most established clinical use for radiolabeled amino acids is imaging primary and recurrent gliomas, and there is growing evidence that they may also be useful for other oncologic applications, including neuroendocrine tumors and prostate cancer. This review focuses on the synthesis, radiolabeling, and preclinical evaluation of three series of nonnatural radiohalogenated amino acids: alicyclic, α,α-dialkyl, and 1H-[1,2,3]triazole amino acids which target system L, system A, and cationic amino acid transport systems, respectively.

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Section: Fluorine‐18 and Radioiodinated αα‐Dialkyl Amino Acidsmentioning

confidence: 99%

Section: Fluorine‐18 and Radioiodinated αα‐Dialkyl Amino Acidsmentioning

confidence: 99%

Radiohalogenated nonnatural amino acids as PET and SPECT tumor imaging agents

McConathy

Jarkas

et al. 2011

Medicinal Research Reviews

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“…18 Synthesis of sulfamidates 18 and 25. 9 The PMB protecting group of (R)-17 was then removed using CAN in CH 3 CN (step vi). Steps iii-v were conducted in accordance with our recent publication.…”

Section: Resultsmentioning

confidence: 99%

“…9 The green-brown solution with a white precipitate was stirred for 15 min at 0°C and allowed to return to rt. The crude sulfamidite 16 (10.2 g, 24 mmol) was dissolved in CH 3 CN (500 mL) and the solution was cooled to 0°C.…”

Section: Resultsmentioning

confidence: 99%

Enantioselective synthesis of α-benzylated lanthionines and related tripeptides for biological incorporation into E. coli peptidoglycan

et al. 2014

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The synthesis of modified tripeptides (S)-Ala-γ-(R)-Glu-X, where X = (R,S) or (R,R) diastereomers of α-benzyl or α-(4-azidobenzyl)lanthionine, was carried out. The chemical strategy involved the enantioselective alkylation of a 4-MeO-phenyloxazoline. The reductive opening of the alkylated oxazolines, followed by cyclization and oxidation, led to four PMB-protected sulfamidates. Subsequent PMB removal, Boc protection and regioselective opening with cysteine methyl ester led to protected lanthionines. These compounds were further converted in a one pot process to the corresponding protected tripeptides. After ester and Boc deprotection, the four tripeptides were evaluated as potential analogues of the natural tripeptide (S)-Ala-γ-(R)-Glu-meso-A2pm. These compounds were evaluated for introduction, by means of the biosynthetic recycling pathway, into the peptidoglycan of Escherichia coli. A successful in vitro biosynthesis of UDP-MurNAc-tripeptides from the tripeptides containing α-benzyl lanthionine was achieved using purified murein peptide ligase (Mpl). Bioincorporation into E. coli W7 did not occur under different tested conditions probably due to the bulky benzyl group at the Cα carbon of the C-terminal amino acid.

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“…Strongly basic organometallic compounds, such as organolithium or Grignard reagents, usually lead to rapid isomerization of epoxides to enolates [292] or to allyl alcoholates. 103 Scheme 4.65. Highly substituted epoxides are particularly prone to such transformations.…”

Section: Epoxide Opening By Carbon Nucleophilesmentioning

confidence: 99%

Aliphatic Nucleophilic Substitutions: Problematic Electrophiles

Dörwald

2004

Side Reactions in Organic Synthesis

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Nucleophilic substitutions at sp 3 -hybridized carbon are among the most useful synthetic transformations, and have been thoroughly investigated [1][2][3]. The success of these reactions depends mainly on the structures of the nucleophile and electrophile, their concentration, and on the solvent and reaction temperature chosen. The structure of the electrophile in nucleophilic substitutions is of critical importance, because many unwanted side reactions result from unexpected reactivity of the electrophile.In Scheme 4.1 the mechanisms of typical monomolecular (Sn1) and bimolecular (Sn2) nucleophilic substitutions at a neutral electrophile with an anionic nucleophile are sketched. Sn1 reactions usually occur when the electrophile is sterically

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Generation of unnatural α,α-disubstituted amino acid derivatives from cyclic sulfamidates

Cited by 49 publications

References 22 publications

Radiohalogenated nonnatural amino acids as PET and SPECT tumor imaging agents

Radiohalogenated nonnatural amino acids as PET and SPECT tumor imaging agents

Enantioselective synthesis of α-benzylated lanthionines and related tripeptides for biological incorporation into E. coli peptidoglycan

Aliphatic Nucleophilic Substitutions: Problematic Electrophiles

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