856865-54-8

Upstream product

• 2389-48-2 N-ε-tert-butoxycarbonyl-L-lysine methyl ester hydrochloride 
• 1694-92-4 2-Nitrobenzenesulfonyl chloride 
• 67-56-1 methanol 
• 71989-26-9 Fmoc-Lys(tert-butoxycarbonyl) 
• 3017-32-1 (S)-methyl 2-amino-6-(tert-butoxycarbonylamino)hexanoate 

Downstream Products

• 1639888-00-8 C₂₈H₄₄N₄O₁₀S 
• 856865-90-2 N-α-methyl-N-α-(o-nitrobenzenesulfonyl)-N-ε-butyloxycarbonyl-L-lysine 
• 856865-68-4 N-methyl-N-(o-nitrobenzenesulfonyl)-N-ε-butyloxycarbonyl-L-lysine methyl ester 

Relevant academic research and scientific papers

Environmentally Friendly SPPS II: Scope of Green Fmoc Removal Protocol Using NaOH and Its Application for Synthesis of Commercial Drug Triptorelin

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.

'Clickable' 2,5-diketopiperazines as scaffolds for ligation of biomolecules: Their use in Aβ inhibitor assembly

The synthesis of 1,3,6-trisubstituted-2,5-diketopiperazine scaffolds bearing up to three 'clickable' sites for further oxime bond or alkyne-azide cycloaddition ligations is described. The orthogonally Boc/Alloc protected DKP precursors prepared from l-lysine residues and an aminohexyl arm are efficiently prepared on a gram scale by sequentially using Fukuyama-Mitsunobu alkylation, dipeptide coupling and diketopiperazine ring formation as key steps. These scaffolds, with their glyoxylyl, aminooxy, alkynyl or azido functions, are ready-to-use platforms for biomolecular assembly. Their potentiality in this field was proved through the chemoselective ligation of Aβ-binding motifs, the KLVFFA peptide and the curcumin molecule. The inhibitory effect of these conjugates on Aβ amyloid fibril formation is reported using thioflavin T fluorescence assays and AFM observation. This journal is the Partner Organisations 2014.

Convenient synthesis of N-methylamino acids compatible with Fmoc solid-phase peptide synthesis

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/