Asymmetric Synthesis of (<i>S</i>)‐5,5,5,5′,5′,5′,5′‐Hexafluoroleucine

Zhang, Cong; Ludin, Christian; Eberle, Marcel K.; Stœckli-Evans, Helen; Keese, Reinhart

doi:10.1002/hlca.19980810116

Cited by 23 publications

(22 citation statements)

References 29 publications

(6 reference statements)

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“…Since size and hydrophobicity are known to be essential factors for secondary structure formation, we compared 5-F 3 Ile with previously studied (2 S ,3 S )-4’-F 3 Ile [13], as well as with ( S )-5,5,5,5’,5’,5’-hexafluoroleucine (F 6 Leu), which was prepared according to procedures reported by Keese and coworkers [25]. …”

Section: Resultsmentioning

confidence: 99%

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

Erdbrink¹,

Nyakatura²,

Huhmann³

et al. 2013

Beilstein J. Org. Chem.

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SummaryA practical route for the stereoselective synthesis of (2S,3S)-5,5,5-trifluoroisoleucine (L-5-F3Ile) and (2R,3S)-5,5,5-trifluoro-allo-isoleucine (D-5-F3-allo-Ile) was developed. The hydrophobicity of L-5-F3Ile was examined and it was incorporated into a model peptide via solid phase peptide synthesis to determine its α-helix propensity. The α-helix propensity of 5-F3Ile is significantly lower than Ile, but surprisingly high when compared with 4’-F3Ile.

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Section: Resultsmentioning

confidence: 99%

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

Erdbrink¹,

Nyakatura²,

Huhmann³

et al. 2013

Beilstein J. Org. Chem.

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“…Although various procedures for synthesizing (S)-5,5,5,5Ј,5Ј,5Ј-hexafluoroleucine (Hfl) have been reported, [40][41][42][43] the development of new methodologies to prepare its fluorinated analogues with more favorable helix propensities remains intensive and challenging because research demonstrated that these helix propensities were drastically reduced upon replacement of Leu with Hfl. In 2007, Scheme 14. Cheng and Chiu developed short chemoenzymatic syntheses both of (S)-Hfl (137, Scheme 15) and of (S)-5,5,5Ј,5Ј-tetrafluoroleucine (Qfl, 138) on gram scales.…”

Section: Trifluorinated and Perfluorinated α-Amino Acidsmentioning

confidence: 99%

Recent Advances in the Synthesis of Fluorinated Amino Acids

2011

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Introduction of fluorine atoms or fluorine‐containing groups into amino acids has attracted much attention from bioorganic and medicinal chemists because the resulting fluorinated amino acids have found wide application as potential enzyme inhibitors and antitumor (antibacterial) agents. Additionally, it is well known that replacement of naturally occurring amino acid(s) in some peptide chains with their fluorinated counterparts can significantly increase specific protein–ligand or protein–protein interactions, leading to increases in the proteolytic and thermal stabilities of peptide compounds and, as a result, promote their therapeutic properties. This microreview summarizes important advances in the synthesis of fluorinated amino acids since 2005. The contents are simply divided into three groups on the basis of amino acid types: fluorinated α‐amino acids (F‐αAAs), fluorinated β‐amino acids (F‐βAAs), and fluorinated cyclic amino acids (F‐CAAs).

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“…After 2 h, the solid was filtered off to give 7.7 g (59%) of 6d, containing 3% of 6c (NMR). The N-acylation of 7b · HCl with (À)-(S)-Moshers acid chloride was performed as described for the acylation of 7a · HCl with (þ)-(R)-Moshers acid chloride [8].…”

Section: Experimental Partmentioning

confidence: 99%

“…The ready access to chiral hexafluorovaline is based on the observation by Knunjants et al [3a] that b,b-bis(trifluoromethyl)acrylate reacts with NH 3 in the a-position of the C¼C bond. Hexafluoroacetone was used as the starting material for our preparation of (S)-5,5,5,5',5',5'-hexafluoroleucine [8].…”

mentioning

confidence: 99%

Stereoselective Synthesis of [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐D‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐L‐valine]cyclosporin A

Eberle

Keese

2010

Helvetica Chimica Acta

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Addition of various amines to the 3,3‐bis(trifluoromethyl)acrylamides 10a and 10b gave the tripeptides 11a–11f, mostly as mixtures of epimers (Scheme 3). The crystalline tripeptide 11f2 was found to be the N‐terminal (2‐hydroxyethoxy)‐substituted (R,S,S)‐ester HOCH2CH2O‐D‐Val(F6)‐MeLeu‐Ala‐OtBu by X‐ray crystallography. The C‐terminal‐protected tripeptide 11f2 was condensed with the N‐terminus octapeptide 2b to the depsipeptide 12a which was thermally rearranged to the undecapeptide 13a (Scheme 4). The condensation of the epimeric tripeptide 11f1 with the octapeptide 2b gave the undecapeptide 13b directly. The undecapeptides 13a and 13b were fully deprotected and cyclized to the [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐D‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐hexafluoro‐N‐(2‐hydroxyethoxy)‐L‐valine]]cyclosporins 14a and 14b, respectively (Scheme 5). Rate differences observed for the thermal rearrangements of 12a to 13a and of 12b to 13b are discussed.

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Asymmetric Synthesis of (S)‐5,5,5,5′,5′,5′,5′‐Hexafluoroleucine

Cited by 23 publications

References 29 publications

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

Recent Advances in the Synthesis of Fluorinated Amino Acids

Stereoselective Synthesis of [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐D‐valine]]‐ and [5‐[4,4,4,4′,4′,4′‐Hexafluoro‐N‐(2‐hydroxyethoxy)‐L‐valine]cyclosporin A

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