Synthesis of Nα-Tetrachlorophthaloyl (TCP)-Protected Amino Acids under Microwave Irradiation (MWI)

Cros, Esther; Planas, Marta; Bardajı́, Eduard

doi:10.1055/s-2001-15215

Cited by 10 publications

(6 citation statements)

References 7 publications

(11 reference statements)

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“…Removal of TCP with EDA partially deprotected the Fmoc group as well, which is not an issue if both groups are detached at the final step from the solid support. However, and in contrast to literature, [20,22] in our hands the TCP functionality turned out to be unstable towards nucleophilic amines, such as piperidine or morpholine used during Fmoc and Alloc groups removal. Based on HPLC-MS results, the side product structure was proposed to derive from the nucleophilic attack of such amines to the phthalimide moiety (see ESI, Section 4d, Scheme S1).…”

Section: Compatibility Among the Different Functionalities And Reaction Conditionscontrasting

confidence: 87%

An Optimized Protocol for the Synthesis of Peptides Containing trans‐Cyclooctene and Bicyclononyne Dienophiles as Useful Multifunctional Bioorthogonal Probes

La–Venia

Dzijak

Rampmaier

et al. 2021

Chemistry A European J

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The synthetic availability and functional diversity of peptides make these biomacromolecules an attractive modality with properties that, in many aspects, lie between antibodies and small synthetic molecules.Traditional solid phase peptide synthesis (SPPS) has been used for decades for construction of natural and functionalized peptides, which found utility in medicinal chemistry, biochemistry, polymer sciences, chemical biology and other disciplines. Despite the great advances in SPPS, the incorporation of certain functional groups into peptide sequences is restricted by the compatibility of the building blocks with conditions used during SPPS. In particular, the introduction of highly reactive groups used in modern bioorthogonal reactions into peptides remains elusive. Here we present an optimized synthetic protocol enabling installation of two strained dienophiles, trans-cyclooctene and bicyclononyne, into different peptide sequences. The two groups enable fast, modular and bioorthogonal post-synthetic functionalization of peptides, as we demonstrate in preparation of peptide-peptide conjugates, peptidedrug conjugates as well as smart, multifunctional chemical biology probes. The presented strategy will find utility in construction of peptides for diverse applications, where high reactivity, efficiency and biocompatibility of the modification step is critical.

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Section: Compatibility Among the Different Functionalities And Reaction Conditionscontrasting

confidence: 87%

An Optimized Protocol for the Synthesis of Peptides Containing trans‐Cyclooctene and Bicyclononyne Dienophiles as Useful Multifunctional Bioorthogonal Probes

La–Venia

Dzijak

Rampmaier

et al. 2021

Chemistry A European J

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“…Solid-phase synthesis of c(DAP-TCP-Gln) (14) elsewhere. [32] Side-chain protection for trifunctional amino acids was as follows: tert-butyl (OtBu) ester for Asp, tert-butyl (tBu) ethers for Ser, Thr, and Tyr. Polymer-supported reactions were carried out using plastic syringes (1, 5, or 10 mL) fitted with polypropylene frits with Teflon-lined caps.…”

Section: Methodsmentioning

confidence: 99%

“…[3,21,29,32,34,35] TCP-amino acids for solid-phase peptide synthesis and other experiments were prepared as described Purity (%) [b] Yield (%) [a] HPLC retention time (condition A).…”

Section: Methodsmentioning

confidence: 99%

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N‐Tetrachlorophthaloyl (TCP) Protection for Solid‐Phase Peptide Synthesis

et al. 2004

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The N‐tetrachlorophthaloyl‐(TCP‐)amino protecting group has been evaluated for use in solid‐phase peptide synthesis. The TCP group was unaffected by exposure to either piperidine or N,N‐diisopropylethylamine (DIEA), which suggests compatibility with both Fmoc and Boc solid‐phase synthesis protocols. Quantitative TCP removal was achieved by treatment with hydrazine/DMF (3:17) at 35 °C for 30 min or with ethylenediamine/DMF (1:200) at 50 °C for 30 min. Several C‐terminal peptide amides were synthesized successfully by following protocols that use hydrazine/DMF (3:17) at 40 °C for 1 h for repetitive deprotection. Treatment of TCP‐amines with methylamine or with diamines did not give the corresponding amines (deprotected), but rather the appropriate N,N′‐disubstituted tetrachlorophthalamides, which corresponds to a single ring‐opening step. This observation was harnessed to prepare linear and macrocyclic peptide−arene hybrids based on the mild reaction of the parent TCP compound with 1,3‐diaminopropane/DMF (1:49) at 25 °C for 5 min. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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“…Bose et al 98 have described the synthesis of tetrachlorophthalimidoacetic acid as an intermediate in the synthesis of α-amino-β-lactams. More recently, Bardaji et al 99 have tested the stability of the TCP function in comparison with the standard Fmoc and Boc removal conditions as well as to TFA cleavage treatments, demonstrating that the method is suitable for solid phase synthesis of peptides. In some cases, the amount of solvent can be reduced to a few drops, necessary only to moisten the reaction mixture, thereby obtaining high quantities of pure cyclic imides in a matter of hours.…”

Section: Scheme 11mentioning

confidence: 99%

Microwave-promoted synthesis of cyclic imides

Perillo¹,

Shmidt²,

Prieto³

et al. 2018

Arkivoc

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Cyclic imides have been extensively investigated because of the wide range of biological activities they exert, as well as due to their importance as synthetic intermediates. Nowadays, focus has been placed on this important class of compounds for their potential new applications, especially in the area of pharmaceutical chemistry. Consequently, the strategies applied for the synthesis of these compounds have attracted considerable attention. Several innovative methodologies have been developed to obtain and functionalize this class of compounds. The use of microwave heating, which is an environmentally harmless strategy, has been making successful inroads in many chemistry areas, such as organic synthesis. Herein we present an update of the microwave-promoted methods for the synthesis of cyclic imides.

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Synthesis of Nα-Tetrachlorophthaloyl (TCP)-Protected Amino Acids under Microwave Irradiation (MWI)

Abstract: A range of N a -tetrachlorophthaloyl protected amino acids have been synthesized by an easy and efficient condensation procedure of the corresponding amino acid and tetrachlorophthaloyl anhydride under irradiation in an unmodified commercial microwave oven.

Cited by 10 publications

References 7 publications

An Optimized Protocol for the Synthesis of Peptides Containing trans‐Cyclooctene and Bicyclononyne Dienophiles as Useful Multifunctional Bioorthogonal Probes

An Optimized Protocol for the Synthesis of Peptides Containing trans‐Cyclooctene and Bicyclononyne Dienophiles as Useful Multifunctional Bioorthogonal Probes

N‐Tetrachlorophthaloyl (TCP) Protection for Solid‐Phase Peptide Synthesis

Microwave-promoted synthesis of cyclic imides

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