The Mixed Carbonic Anhydride Method of Peptide Synthesis

Meienhofer, Johannes

doi:10.1016/b978-0-12-304201-9.50012-6

Cited by 19 publications

(19 citation statements)

References 160 publications

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“…methylmorpholine) and p-iodoaniline in THF and recrystallized H-atoms were placed at calculated positions and refined as riding from hot heptane/THF (10:1). [73] Ϫ Melting points (uncorrected) atoms with isotropic displacement parameters. All crystallographic were determined in a Tottoli apparatus (Büchi, Switzerland).…”

Section: Spectroscopy and Discussionmentioning

confidence: 99%

A Two-Step Palladium-Catalyzed Coupling Scheme for the Synthesis of Ferrocene-Labeled Amino Acids

Brosch

Weyhermüller

Metzler‐Nolte³

2000

Eur. J. Inorg. Chem.

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This work describes a Pd‐catalyzed coupling of ferrocene alkyne derivatives to iodo amino acids. Ferrocene carboxylic acid propargyl amides were easily obtained in high yield. The crystal structures of the propargyl amine derivative 3 and the 1,1‐diethylpropargylamine derivative 4 have been determined by X‐ray diffraction. Pd‐catalyzed coupling to p‐iodoanilide amino acids gave the corresponding ferrocene‐labeled amino acid derivatives, which were easily purified by diethyl ether extraction in the case of the 1,1‐diethyl derivatives 8. The coupling reaction did not require anhydrous solvents and tolerated a variety of functional groups present in peptides such as alcohols (8a, Ser), thioethers (8d, Met), disulfide bonds (cystine, 12) esters (as in the N‐labeled Leu derivative 10) and of course amides. A minor by‐product of the coupling reaction, namely the homo‐dimer bis(ferrocene carboxylic acid propargylamide) 9, was identified in the crude reaction mixtures by mass spectrometry and independently synthesized by oxidative coupling (Glaser and Eglington) of 3. All new compounds were completely characterized spectroscopically, including 15N‐ and 2D NMR spectroscopy, Mössbauer spectroscopy and electrochemistry. This work introduces a versatile procedure for a selective functionalization of amino acids with organometallics at the C‐terminus which is expected to be of general applicability to peptide chemistry.

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Section: Spectroscopy and Discussionmentioning

confidence: 99%

A Two-Step Palladium-Catalyzed Coupling Scheme for the Synthesis of Ferrocene-Labeled Amino Acids

Brosch

Weyhermüller

Metzler‐Nolte³

2000

Eur. J. Inorg. Chem.

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“…The dipeptide Boc-Ala-Phe-OMe was prepared according to standard peptide chemistry techniques from Boc-Ala-OH and H-Phe-OMeؒHCl, employing isobutylchloroformate as the coupling reagent. 12 The Boc-protecting group of the dipeptide was removed by reaction with CH 2 Cl 2 /CF 3 CO 2 H (1 : 1, v/v) for 1 h at room temperature, followed by removal of the solvent in vacuo, yielding the dipeptide H-Ala-Phe-OMeؒCF 3 CO 2 H as a white hygroscopic solid. The compounds [Co(Cp)(C 5 H 4 -CO 2 H)]PF 6 (1b, Cp = η-C 5 H 5 ) and [Co(C 5 H 4 -CO 2 H) 2 ]PF 6 (2b) were synthesised according to literature methods.…”

Section: Methodsmentioning

confidence: 99%

Organometallic β-turn mimetics. A structural and spectroscopic study of inter-strand hydrogen bonding in ferrocene and cobaltocenium conjugates of amino acids and dipeptides

Staveren¹,

Weyhermüller²,

2003

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“…Compounds with a very low affinity of RFC gave values of ∼1. Using these ratios as precedent we conclude that four compounds (25-27, 36a) with high relative resistance ratios (8)(9)(10) are poor substrates for FPGS. We are not able to say clearly whether a low level of polyglutamation is occurring, and further work with a cell line expressing a low level of FPGS activity or radiolabeled studies would be required to establish this.…”

Section: Resultsmentioning

confidence: 95%

Folate-Based Inhibitors of Thymidylate Synthase: Synthesis and Antitumor Activity of γ-Linked Sterically Hindered Dipeptide Analogues of 2-Desamino-2-methyl-N¹⁰-propargyl-5,8-dideazafolic Acid (ICI 198583)

et al. 1997

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In an effort to synthesize inhibitors of thymidylate synthase (TS) that do not undergo polyglutamation, a series of gamma-linked sterically hindered dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) was prepared. A methyl, ethyl, or propargyl group was incorporated into the gamma-glutamyl amide bond of gamma-linked L,L dipeptide derivatives of ICI 198583, such as ICI 198583-gamma-L-Glu. In addition, steric bulk was introduced on either side of the gamma-glutamyl bond of ICI 198583-gamma-L-Glu or ICI 198583-gamma-L-Ala. The resulting dipeptide analogues, e.g., ICI 198583-gamma-MeGlu and ICI 198583-gamma-Aib, were apparently stable to in vivo hydrolysis but poorer inhibitors of TS and L1210 cell growth. However, introduction of 7-Me, 2'-F substitution into the quinazoline nucleus gave significant improvement in the inhibitory activity against thymidylate synthase. Compounds 28-30, the 7-Me, 2'-F derivatives of ICI 198583-gamma-MeGlu, ICI 198583-gamma-EtGlu, and ICI 198583-gamma-PgGlu, respectively, were potent inhibitors of TS (K(iapp) = 0.21-1.1 nM) and L1210 cell growth (IC50 = 0.05-0.34 microM) and were similar to that seen with the most potent gamma-linked L,D dipeptide derivatives of ICI 198583 previously synthesized. Furthermore, the low cross-resistance ratios for the L1210:R(D1694)/L1210 cell line indicated that 28-30 do not undergo polyglutamation.

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The Mixed Carbonic Anhydride Method of Peptide Synthesis

Cited by 19 publications

References 160 publications

A Two-Step Palladium-Catalyzed Coupling Scheme for the Synthesis of Ferrocene-Labeled Amino Acids

A Two-Step Palladium-Catalyzed Coupling Scheme for the Synthesis of Ferrocene-Labeled Amino Acids

Organometallic β-turn mimetics. A structural and spectroscopic study of inter-strand hydrogen bonding in ferrocene and cobaltocenium conjugates of amino acids and dipeptides

Folate-Based Inhibitors of Thymidylate Synthase: Synthesis and Antitumor Activity of γ-Linked Sterically Hindered Dipeptide Analogues of 2-Desamino-2-methyl-N¹⁰-propargyl-5,8-dideazafolic Acid (ICI 198583)

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The Mixed Carbonic Anhydride Method of Peptide Synthesis

Cited by 19 publications

References 160 publications

A Two-Step Palladium-Catalyzed Coupling Scheme for the Synthesis of Ferrocene-Labeled Amino Acids

A Two-Step Palladium-Catalyzed Coupling Scheme for the Synthesis of Ferrocene-Labeled Amino Acids

Organometallic β-turn mimetics. A structural and spectroscopic study of inter-strand hydrogen bonding in ferrocene and cobaltocenium conjugates of amino acids and dipeptides

Folate-Based Inhibitors of Thymidylate Synthase: Synthesis and Antitumor Activity of γ-Linked Sterically Hindered Dipeptide Analogues of 2-Desamino-2-methyl-N10-propargyl-5,8-dideazafolic Acid (ICI 198583)

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Folate-Based Inhibitors of Thymidylate Synthase: Synthesis and Antitumor Activity of γ-Linked Sterically Hindered Dipeptide Analogues of 2-Desamino-2-methyl-N¹⁰-propargyl-5,8-dideazafolic Acid (ICI 198583)