- Environmentally Friendly SPPS II: Scope of Green Fmoc Removal Protocol Using NaOH and Its Application for Synthesis of Commercial Drug Triptorelin
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With the growing necessity to consider environmental impacts when synthesizing peptide-based drugs and to expand upon the recently published short communication report, we herein present a thorough evaluation of a green Fmoc removal protocol. Our protocol avoids the use of hazardous components (using piperidine as a base and dichloromethane (DCM) and N,N-dimethylformamide (DMF) as solvents) and relies on the utilization of the green mineral base NaOH in combination with the greener solvent 2-methyltetrahydrofuran (2-MeTHF) mixed with MeOH. For the original Fmoc removal cocktail (solvents ratio of 1:1), we evaluated the impact of quality/purity of the used 2-MeTHF, scale-up, ratio of 2-MeTHF/MeOH, utilized hydroxide, temperature, and reaction time. An alternative 3:1 protocol was examined using various amino acids, and only Gly required the optimization of the Fmoc removal cocktail composition. The optimized protocol used to remove Fmoc from Gly residue was proved by the synthesis of Leu-enkephalin. We also investigated the stability of the conventional amino acid side-chain-protecting groups, t-Bu, Boc, Trt, and Pbf, and the formation of aspartimide as an undesirable side reaction that occurs during Fmoc solid-phase peptide synthesis (SPPS). The applicability of this synthesis strategy was documented by evaluating the SPPS of a commercial drug used for prostate and breast cancer treatments - decapeptide triptorelin.
- P?ibylka, Adam,Krchňák, Viktor,Schütznerová, Eva
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p. 8798 - 8811
(2020/09/09)
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- Convenient synthesis of N-methylamino acids compatible with Fmoc solid-phase peptide synthesis
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Nα-Methylamino acid containing peptides exhibit interesting therapeutic profiles and are increasingly recognized as potentially useful therapeutics. Unfortunately, their synthesis is hampered by the high price and unavaibility of many Nα/
- Biron, Eric,Kessler, Horst
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p. 5183 - 5189
(2007/10/03)
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- Amino acid derived intramolecular 1,3-dipolar cycloadditions that form bridged medium ring systems with diastereoselective control
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Intramolecular nitrone cycloadditions using amino acid precursors, generate aminohydroxyazepine and amino hydroxypiperidine templates. The cycloaddition reactions yield either a [4.3.0] fused system or in most cases a [4.2.1] bridged system. The [4.2.1] bridged system allows for the stereospecific preparation of 3-amino-5-hydroxyazepines while the [4.3.0] system allows for the preparation of 3-amino-5-hydroxymethyl piperidines.
- Liu, Yanbin,Maden, Amy,Murray, William V
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p. 3159 - 3170
(2007/10/03)
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