Recent Advances in the Asymmetric Synthesis of α-(Trifluoromethyl)-Containing α-Amino Acids

Aceña, José Luis; Sorochinsky, Alexander E.; Soloshonok, Vadim A.

doi:10.1055/s-0031-1289756

Cited by 157 publications

(41 citation statements)

References 18 publications

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“…Certain conformations, avoiding steric and electrostatic interactions can be favoured, and from a metabolic point of view, the incorporation of fluorine can improve the oxidative and proteolytic stability, while increasing the lipophilicity . As a consequence, the synthesis of fluorinated amino acids and their incorporation into peptides has attracted a great deal of interest within the peptide‐chemistry field . More recently, fluorinated analogues of amino acids have also received particular attention in the structural study of peptides by using 19 F‐NMR spectroscopy ,…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Synthesis of Cyclic Fluorinated Amino Acids

et al. 2018

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A methodology for the asymmetric synthesis of CF3‐β‐proline and CF3‐six‐membered cyclic amino acids has been developed starting from readily available N‐tert‐butanesulfinyl‐(3,3,3)‐trifluoroacetaldimine. The Zn‐mediated allylation followed by an intramolecular 5‐endo‐trig cyclisation afforded the CF3‐β‐proline, whereas the CF3‐six‐membered cyclic amino acids were obtained by using a ring‐closing‐metathesis protocol of CF3‐aminodienes.

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Section: Introductionmentioning

confidence: 99%

Asymmetric Synthesis of Cyclic Fluorinated Amino Acids

et al. 2018

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“…The fluorinated α- or acyclic β-amino acids have acquired significance as antibacterial or antifungal agents, enzyme inhibitors or as antitumoral compounds. Introduction of a fluorinated amino acid into a peptide may generate specific protein–ligand or protein–protein interactions, thereby determining thermal or metabolic stabilities, which is of great importance in peptide-based drug research [11–35]. These changes in properties may be more appreciable in the case of peptide oligomers formed from conformationally restricted fluorinated amino acids.…”

Section: Introductionmentioning

confidence: 99%

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

Kiss¹,

Nonn²,

Sillanpää³

et al. 2013

Beilstein J. Org. Chem.

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SummaryA regio- and stereoselective method has been developed for the synthesis of novel fluorinated 2-aminocyclohexanecarboxylic acid derivatives with the fluorine attached to position 4 of the ring. The synthesis starts from either cis- or trans-β-aminocyclohex-4-enecarboxylic acids and involves regio- and stereoselective transformation of the ring C–C double bond through iodooxazine formation and hydroxylation, followed by hydroxy–fluorine or oxo–fluorine exchange.

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“…For instance, the authors were forced [13][14][15][16][17][18] to use the archaic ᴅ/ʟ system to avoid confusion when describing the haloalanines thus rendering it impractical to maintain the use of only one system. Moreover, the number of such cases has grown exponentially due to the efforts of synthetic chemists in producing a large number [9][10][11][12]19,20 of tailor-made α-amino acids 21 whereby fluorine-containing amino acids [22][23][24][25] in particular have been utilized by the pharmaceutical industry, 26,27 in medical research, and for other applications. With new synthetic compounds or compounds isolated from natural sources, the perception of the wrong stereochemistry is easily misconstrued by readers due to the changing R/S descriptors without necessary explanation by the author(s) or due care taken by the readers.…”

Section: Examples Of Sp 3 -Hybridized Tetrahedral Chiral Structuresmentioning

confidence: 99%

Internal chirality descriptors iR and iS and ire and isi. A proposed notation to extend the usefulness of the R/S system by retaining the sense of stereochemistry in cases of ligand ranking changes

2018

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The R/S system, universally applied for indicating the absolute configuration of a structure, is extremely adept for conveying the absolute configuration unequivocally. However, it suffers from one limitation, viz that due to CIP priority rules the rankings of the ligands attached to an asymmetric center can be altered upon a change in a ligand leading to a change in the designated configuration even if bonds to the asymmetric center were not actually formed or broken. This means that the sense of stereochemistry in situations such as within a set of compounds where family relationships are of focus or where the sense of the stereochemical course of a reaction is of interest can be lost or confusion may occur. This shortcoming is easily remedied though by defining a fixed ranking for a particular ligand in the system under study, eg, the ligand at which the change has occurred. The configurations are then expressed as iR or iS, akin to the R and S descriptors, for sp -hybridized tetrahedral chiral structures and similarly, as ire and isi faces, akin to the re and si descriptors, for sp -hybridized trigonal prochiral structures. All in all, the notation can be considered as an auxiliary to extend the usefulness of the R/S system. Thus, the proposed iR/iS notation could find profitable use in comparative studies where there is a need to avoid confusion arising from changing assignments due to priority rules or to expedite the ease of comprehension. Moreover, in the current digital age, the facile retrieval of stereochemically clear data by machines is highly desirable-something that the iR/iS notation is readily amenable to.

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Recent Advances in the Asymmetric Synthesis of α-(Trifluoromethyl)-Containing α-Amino Acids

Cited by 157 publications

References 18 publications

Asymmetric Synthesis of Cyclic Fluorinated Amino Acids

Asymmetric Synthesis of Cyclic Fluorinated Amino Acids

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

Internal chirality descriptors iR and iS and ire and isi. A proposed notation to extend the usefulness of the R/S system by retaining the sense of stereochemistry in cases of ligand ranking changes

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