149207-52-3Relevant academic research and scientific papers
Synthesis of a new molecular carrier: N-(Leu-enkephalin)yl 6-amido-6-deoxy-cyclomaltoheptaose
Djedaini-Pilard, Florence,Desalos, Jacques,Perly, Bruno
, p. 2457 - 2460 (1993)
The synthesis of N-(Leu-enkephalin)yl 6-amido-6-deoxy-cyclomaltoheptaose has been performed in high yield. The final derivative has been characterized by proton NMR in terms of chemical and inclusion properties and represents a new class of target-directed transporters.
Cleaving protected peptides from 2-chlorotrityl chloride resin. Moving away from dichloromethane
Alhassan, Mahama,Al Musaimi, Othman,Collins, Jonathan M.,Albericio, Fernando,De La Torre, Beatriz G.
supporting information, p. 2840 - 2845 (2020/06/17)
In recent years, the work of various research groups has allowed the substitution of the hazardous solvents most widely used in solid-phase peptide synthesis, namely DMF, NMP, DCM, DEE, among others, by several much less hazardous solvents. Indeed, greener alternatives have been found for almost all steps of the process, with the exception of the cleavage of protected peptides from 2-chlorotrityl chloride resin. Here, after careful screening of several of the so-called green solvents, we propose 2% TFA in either anisole or 1,3-dimethoxybenzene as optimal for the cleavage step. The higher boiling point of these solvents compared with the DCM allows the preparation of protected peptides with less risk of premature removal of the most labile protecting groups, such as the Trt of His. Our findings once again evidence the value/versatility of green solvents in strict chemical terms.
Thiophene backbone amide linkers, a new class of easily prepared and highly acid-labile linkers for solid-phase synthesis
Jessing, Mikkel,Brandt, Malene,Jensen, Knud J.,Christensen, Jorn B.,Boas, Ulrik
, p. 6734 - 6741 (2007/10/03)
Solid-phase synthesis is of tremendous importance for small-molecule and biopolymer synthesis. Linkers (handles) that release amide-containing products after completion of solid-phase synthesis are widely used. Here we present a new class of highly acid-labile backbone amide linkers (BAL handles) based on 3,4-ethylenedioxythiophene (EDOT), which we have termed T-BAL. These thiophene linkers are synthesized in three convenient steps from commercially available EDOT. In the linker design, the spacer was introduced to the EDOT core either via a carbon-carbon bond or via a thioether linkage. Introduction of the spacer via a C-C bond was performed by a chemoselective Negishi coupling without transient protection of the aldehyde group to provide the T-BAL1 handle. Introduction via a thioether linkage was performed by a facile nucleophilic aromatic substitution between the brominated EDOT aldehyde and unprotected mercapto acids to provide T-BAL2 and T-BAL3 handles. The minimal use of protecting groups gave the corresponding linker molecules in few synthetic steps and in good yields. After anchoring of the linker to a polymeric support, introduction of the first amino acid was achieved by reductive amination, giving a secondary amine. A following acylation of the secondary amine with a symmetrical amino acid anhydride resulted in a backbone amide linkage between the handle and the growing substrate (e.g., peptide chain). After solid-phase synthesis, the substrates could be released from the resin by either low acid conditions using 1% TFA in CH2Cl2 or high acid conditions such as 50% TFA in CH2Cl2. Peptide thioesters could be released from the T-BAL1 handle under very mild conditions using aqueous acetic acid. Tert-butyl based protecting groups, tert-butyl esters, tert-butyl ethers, and Boc groups, as well as dimethyl acetals were relatively stable to these mild conditions for release of the peptides.
