101644-79-5Relevant articles and documents
Trimethyl-substituted carbamate as a versatile self-immolative linker for fluorescence detection of enzyme reactions
Inoue, Kazuya,Nakamura, Noriaki,Ojida, Akio,Uchinomiya, Shohei
supporting information, (2020/05/25)
Self-immolative linker is a useful building block of molecular probes, with broad applications in the fields of enzyme activity analysis, stimuli-responsive material science, and drug delivery. This manuscript presents N-methyl dimethyl methyl (i.e., trimethyl) carbamate as a new class of self-immolative linker for the fluorescence detection of enzyme reactions. The trimethyl carbamate was shown to spontaneously undergo intramolecular cyclization upon formation of a carboxylate group, to liberate a fluorophore with the second time rapid reaction kinetics. Interestingly, the auto-cleavage reaction of trimethyl carbamate was also induced by the formation of hydroxyl and amino groups. Fluorescent probes with a trimethyl carbamate could be applicable for fluorescence monitoring of the enzyme reactions catalyzed by esterase, ketoreductase, and aminotransferase, and for fluorescence imaging of intracellular esterase activity in living cells, hence demonstrating the utility of this new class of self-immolative linker.
Highly efficient synthesis of sterically hindered peptides containing N-methylated amino acid residues using a novel 1H-benzimidazolium salt
Li, Peng,Xu, Jie Cheng
, p. 9949 - 9955 (2007/10/03)
Novel 1H-benzimidazolium type peptide coupling reagent, CMBI, was designed, synthesized, and shown to be efficient in the promotion of the formation of sterically hindered amide and ester bonds. Its high efficiency was proved by model reaction tests and the successful synthesis of various hindered oligopeptides and peptide segments containing N-methyl amino acid residues with fast reaction speeds, low racemization and excellent yields. A mechanism for amide bond formation mediated by the reagent was proposed. (C) 2000 Elsevier Science Ltd.
A Short Synthesis of Enantiomerically Pure (2S,3R,4R,6E)-3-Hydroxy-4-methyl-2-(methylamino)-6-octenoic Acid, the Unusual C-9 Amino acid Found in the Immunosuppressive Peptide Cyclosporine
Aebi, Johannes D.,Dhaon, Madhup K.,Rich, Daniel H.
, p. 2881 - 2886 (2007/10/02)
A new and efficient synthesis of enantiomerically pure (2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6-octenoic acid (MeBmt, 2) is reported.Reaction of (2R,4E)-2-methyl-4-hexenal (6c) with p-methoxybenzyloxycarbonylsarcosine tert-butyl ester (Pmz-Sar-O-t-Bu, 5) gave MeBmt (2) in 18-20percent overall yield.The lithium enolate of the tert-butyl ester is more stable than the corresponding methyl ester at higher temperature (room temperature vs. -78 deg C) and reacts selectively with aldehydes even in the presence of impurities.Room temperatures conditions were needed in order to increase the desired anti-Cram product 9a.The Pmz group proved superior to other amino protecting groups (e.g., Cbz) because residual Pmz-sarcosine derivatives could be easily removed from products 9a and 9b by cleavage of the Pmz group by reaction with TFA/anisole.This procedure eliminated the need for column chromatography after the aldol reaction.Reaction of the lithium enolate of Pmz-Sar-O-t-Bu (5) with aldehyde 6c afforded only the two trans-substituted 2-oxazolidinones 9a and 9b and none of the cis-substituted 2-oxazolidinones.The chemically pure diastereomeric mixture of 2-oxazolidinones 9a and 9b was resolved by using (1S,2R)-(+)-ephedrine to give enantiomerically and diastereomerically pure 9a in 18-20percent overall yield (from aldehyde 6c).Hydrolysis of 9a gave the desired MeBmt (2) in quantitative yield.This amino acid was incorporated into cyclosporin A (CSA, 1) by known literature procedures.In order to demonstrate that the synthetic methodology described in this paper can be utilized in the synthesis of a number of MeBmt (2) analogues, 1'-desmethyl-2-oxazolidinone 10a was also prepared by similar procedures.
