1824552-06-8Relevant articles and documents
A reappraisal of the Ni-[(Benzylprolyl)amino]benzophenone complex in the synthesis of α,α-disubstituted amino acid derivatives
Watson, Morag E.,Jamieson, Craig,Kennedy, Alan R.,Mason, Andrew M.
, (2019/08/08)
α,α-Disubstituted alkenyl amino acid derivatives (e.g. Fmoc-S5-OH) are valuable monomers in the construction of stapled peptide derivatives. Synthetic access to these is possible using the Ni-[(Benzylprolyl)amino]benzophenone (BPB) complex as a chiral auxiliary. We discuss a reappraisal of the use of this, and demonstrate that epimerisation of the proline α-centre occurs during formation of the complex, leading to erosion in the enantiomeric excess of the final product. Modified conditions have been developed, providing the target compounds in high enantiomeric excess.
Improved synthesis of unnatural amino acids for peptide stapling
Li, Bo,Zhang, Jie,Xu, Yongjuan,Yang, Xiaoxiao,Li, Li
supporting information, p. 2374 - 2377 (2017/05/29)
The procedures for the synthesis of various α-alkenyl and alkyne amino acids were systematically optimized in light of enhancing atom economy, reducing hazardous reagent usage, and simplifying workup. By starting with Boc-Pro-OH and coupling with EDCI/DMAP followed by alkylation, chiral auxiliary was synthesized with high yield and enantioselectivity. For alkylation of the chiral complex, tBuONa was found and proved by quantitative calculation to be superior to tBuOK in generating more nucleophilic enolate salt, thereby can significantly enhance yield under room temperature. Final Fmoc protection was also dramatically facilitated in one-pot sequential manner by adding EDTA-2Na as the nickel chelator. Synthesis of α-bisalkenyl amino acid was also accomplished by achiral complex approach with high yield and efficacy. Accordingly, five most commonly used N-Fmoc protected α-alkenyl and alkynyl amino acids were synthesized and characterized.
Influence of α-methylation in constructing stapled peptides with olefin metathesis
Zhang, Qingzhou,Shi, Xiaodong,Jiang, Yanhong,Li, Zigang
, p. 7621 - 7626 (2014/12/11)
Ring-closing metathesis is commonly utilized in peptide macro-cyclization. The influence of α-methylation of the amino acids bearing the olefin moieties has never been systematically studied. In this report, controlled reactions unambiguously indicate that α-methylation at the N-terminus of the metathesis sites is crucial for this reaction to occur. Also, we first elucidated that the E-isomers of stapled peptides are significantly more helical than the Z-isomers.
Robust asymmetric synthesis of unnatural alkenyl amino acids for conformationally constrained α-helix peptides
Aillard, Boris,Robertson, Naomi S.,Baldwin, Adam R.,Robins, Siobhan,Jamieson, Andrew G.
supporting information, p. 8775 - 8782 (2014/12/11)
The efficient asymmetric synthesis of unnatural alkenyl amino acids required for peptide 'stapling' has been achieved using alkylation of a fluorine-modified NiII Schiff base complex as the key step.
Stereoselective access to fluorinated and non-fluorinated quaternary piperidines: Synthesis of pipecolic acid and iminosugar derivatives
Fustero, Santos,Albert, Laia,Mateu, Natalia,Chiva, Gema,Miro, Javier,Gonzalez, Javier,Acena, Jose Luis
experimental part, p. 3753 - 3764 (2012/05/19)
The preparation of optically pure quaternary piperidines, both fluorinated and non-fluorinated, has been achieved from a chiral imino lactone derived from (R)-phenylglycinol. In the case of the fluorinated derivatives, the addition of (trifluoromethyl)trimethylsilane (TMSCF3) followed by iodoamination and migration of the CF3 group allowed access to four derivatives of α-(trifluoromethyl)pipecolic acid. A theoretical study of the CF 3-group rearrangement has been carried out to help establish the reaction mechanism of this uncommon transformation. Moreover, a route to trifluoromethyl-substituted iminosugars was also developed through the diastereoselective dihydroxylation of suitable synthetic intermediates. Conversely, alkylation of the starting substrate and subsequent cross-metathesis and aza-Michael reactions led to α-alkyl derivatives of the target compounds. Copyright
A cross-metathesis route to functionalized α-methyl α-substituted amino acids
Storcken, Roy P. M.,Panella, Lavinia,Van Delft, Floris L.,Kaptein, Bernard,Broxterman, Quirinus B.,Schoemaker, Hans E.,Rutjes, Floris P. J. T.
, p. 161 - 164 (2008/02/03)
A chemoenzymatic approach to the synthesis of functionalized α-methyl α-substituted amino acids is detailed. This involves amidasemediated enzymatic resolution of α-methyl α-substituted side-chain ω-unsaturated amino acids followed by functionalization via cross-metathesis.
