Synthesis of Chiral Spin-Labeled Amino Acids

Abstract

Spin-labeled amino acids (SLAAs) are often used to determine intermolecular distances and conformations in proteins via double electron–electron resonance. Currently available SLAAs can be difficult to incorporate selectively and have little resemblance to natural side chains in proteins. Enantioselective synthesis of three spin-labeled l-amino acids is described, starting from readily available 2,2,6,6-tetramethyl-4-piperidinone. These SLAAs better replicate canonical residues in proteins and aim for biological incorporation via genetic incorporation or solid-phase peptide synthesis.

A One-Pot Method to Prepare 4,5-Benzotropones and 2,3,4,5-Dibenzotropones

“…5-Methylene-dibenzocycloheptene 9 could be prepared from the Wittig reaction of 3f with Ph3P + MeBr in toluene, with the reaction yield up to 89%. 15 Condensation reaction of 3f with hydroxylamine sulfate was carried out in a mixture solvent of EtOH/H2O (5/3), giving dibenzocycloheptenone oxime derivative 10 in 90% yield. 16 Further treatment of 10 with TsCl/Pyridine in DCM could provide a ring expansion product cyclooctene amide 11 in 52% yield.…”

“…uene, with the reaction yield being 89%. 15 The condensation reaction of 3f with hydroxylamine sulfate was carried out in a solvent mixture of EtOH/H 2 O (5:3), giving dibenzocycloheptenone oxime derivative 10 in 90% yield. 16 Further treatment of 10 with TsCl/pyridine in DCM provided the ring-expansion product cyclooctene amide 11 in 52% yield.…”

Reprogramming natural proteins using unnatural amino acids

“…Therefore, an extensive study on enantioselective, catalytic, and chiral pool synthesis of optically pure UAAs has been reported in recent years. [43][44][45][46][47][48][49][50][51] Further study in the design of novel catalysts and chiral auxiliaries, as well as proper selection of chiral precursors for chiral pool synthesis, could enhance the synthesis of chiral UAAs with an excellent enantiomeric excess (ee) and high yield. Consideration of the green chemistry approach towards the asymmetric synthesis of UAAs is highly recommended.…”

“…5d ). 50 In defiance of ecologically unfriendly nature, chemical synthesis is undeniably a non-tedious and robust technique for UAAs synthesis. Henceforth, a minute alternation in chemical procedure with green chemistry would nullify its toxic effects and assuredly be a novel synthetic method for UAAs.…”

Asymmetric Synthesis of Tailor-Made Amino Acids Using Chiral Ni(II) Complexes of Schiff Bases. An Update of the Recent Literature

“…In 2019, enantioselective synthesis of three spin-labeled amino acids ( 62 , 63 , 64 ) ( Figure 3 ) via the Ni complex based strategy was developed by Vederas and co-authors [ 72 ].…”