193954-23-3

Upstream product

• 186581-53-3 diazomethane 
• 103321-50-2 9H-fluoren-9-ylmethyl [(1S)-2-chloro-1-methyl-oxoethyl]carbamate 
• 35661-39-3 N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine 
• 28920-43-6 (fluorenylmethoxy)carbonyl chloride 
• 18107-18-1 diazomethyl-trimethyl-silane 

Downstream Products

• 193954-26-6 (S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid 

Relevant academic research and scientific papers

A new GLP-1 analogue with prolonged glucose-lowering activity in vivo via backbone-based modification at the N-terminus

Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clinical use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone-based modification was rarely reported. Herein, we employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N-methylated analogues 2-6 were designed and synthesized to make a full screening of the N-terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N-terminal amide H-bonds, the β-peptide replacement strategy was used and analogues 7-13 were synthesized. By two rounds of screening, analogue 10 was identified. Analogue 10 greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approximately a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs.

One-pot synthesis of orthogonally protected dipeptide selenazoles employing Nα-amino selenocarboxamides and α-bromomethyl ketones

A simple and efficient protocol for the synthesis of selenazole containing dipeptidomimetics using Nα-amino selenocarboxamides and α-bromomethyl ketones is described. All the compounds made were isolated in good yields and fully characterized.

Synthesis of N-urethane protected α-aminoalkyl-α-cyanomethyl ketones; Application to the synthesis of 3-substituted 5-amino-1H-pyrazole tethered peptidomimetics

The preparation of N-protected amino/peptide α-cyanomethyl ketones through cyanation of the corresponding α-bromomethyl ketones is described. The utility of the resulting α-cyanomethyl ketones in the synthesis of 3-substituted-5-amino-1H-pyrazoles has also been demonstrated. In both steps a wide range of N-protected amino/peptide acids has been employed and the products are obtained in good yield. The enantiomeric purity of both the α-cyanomethyl ketones and pyrazoles were confirmed by chiral HPLC analysis of the corresponding Z-protected d- and l-Ala-OH as model substrates. The synthesis of peptide pyrazolecarboxamides is also delineated. Georg Thieme Verlag Stuttgart · New York.

A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids

The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of N-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that tert-butyloxycarbonyl (Boc), tert-butyl (tBu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding C-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective N-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected dipeptidyl diazoketones.

Ultrasound mediated synthesis of 2-amino-1,3-selenazoles derived from Fmoc/Boc/Z-α-amino acids

A simple and efficient one-pot synthesis of Fmoc/Boc/Z-amino acid derived 2-amino-1,3-selenazoles by the condensation of Nα-urethane protected amino acid derived bromomethyl ketones with selenourea under the influence of ultrasound has been described. Insertion of 2-amino-1,3-selenazole moiety in the side chains of Asp and Glu has also been achieved following the similar protocol. ARKAT USA, Inc.

Small molecule microarray-facilitated screening of affinity-based probes (AfBPs) for γ-secretase

A small molecule microarray (SMM) platform is developed herein, which enables high-throughput discovery of affinity-based probes (AfBPs) against γ-secretase.

Pseudopeptide, synthesis method, reagent and applications

The invention concerns a pseudopeptide of at least 6 amino acids comprising at least a unit selected among the general formulae (I) and/or (II) wherein: R1, R2 and R3 each independently of one another represent a side-chain of amino acids and can be identical or different; X represents an oxygen or sulphur atom. The invention also concerns its synthesis process, a reagent containing it, a detection kit comprising such a reagent, a method for detecting an antigen or an antibody using said pseudopeptide, and antibody or and anti-idiotype and finally a therapeutic composition.

Efficient and direct solid phase synthesis of ketomethylenimino and ketomethylenamino peptides

The reaction between the free amino terminus of a solid-supported peptide and a glyoxal leads to two families of pseudopeptides, the ketomethylenimino and the ketomethylenamino peptides. The aim of this study is the synthesis of pseudopeptides on solid supports, in order to quickly obtain modified peptides. We report a convenient step-by-step synthesis of ketomethylenimino ψ[CO-CH=N] and ketomethylenamino ψ[CO-CH2-NH] peptides. The key is the reaction between the free amino terminus of the supported peptide and a glyoxal-modified amino acid, leading to a ketomethylenimino bond, which can be reduced to a ketomethylenamino bond.

Homologation of α-amino acids to β-amino acids: 9-Fluorenylmethyl chloroformate as a carboxyl group activating agent for the synthesis of Nα-protected aminoacyldiazomethanes

An efficient and stereospecific homologation of urethane-protected α-amino acids to β-amino acids by Arndt-Eistert approach using an equimolar mixture of Fmoc-/Boc-/Z-α-amino acid and 9-fluorenylmethyl chloroformate for the acylation of diazomethane synth

Convenient and simple homologation of Nα-urethane protected α-amino acids to their β-homologues with concomitant o-nitrophenylesters formation

The Wolff rearrangement of α-aminodiazoketones derived from Nα-urethane protected α-amino acids in presence of o-nitrophenol catalyzed by silver acetate at low temperature is described. The potential utility of the well-known ketene intermediat