Chemoenzymatic synthesis of enantiomerically pure 4-fluoro-3-nitro and 3-fluoro-4-nitro phenylalanine

Vergne, Carine; Bois‐Choussy, Michèle; Ouazzani, Jamal; Beugelmans, R.; Zhu, Jieping

doi:10.1016/s0957-4166(96)00524-1

Cited by 33 publications

(26 citation statements)

References 32 publications

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“…Coupling of ( S )‐dopa methyl ester ( 6 ) with ( S , S )‐ N ‐Boc isoleucine ( 7 ) provided the dipeptide 8 in 94 % yield. Subsequent hydrolysis of the methyl ester followed by amidation with the hydrochloride salt of ( S )‐methyl 4‐fluoro‐3‐nitrophenylalanate ( 9 )10 afforded the tripeptide 5 in 78 % overall yield. The size‐selective ring‐forming process based on the intramolecular S N Ar reaction proceeded smoothly 11.…”

Section: Methodsmentioning

confidence: 99%

Honeycomb Self‐Assembled Peptide Scaffolds by the Breath Figure Method

Zhu

Yan

et al. 2011

Chemistry A European J

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The self-assembly of molecules into desired architectures is currently a challenging subject for the development of supramolecular chemistry. Here we present a facile "breath figure" assembly process through the use of the self-assembled peptide building block diphenylalanine (L-Phe-L-Phe, FF). Macroporous honeycomb scaffolds were fabricated, and average pore size could be regulated, from (1.00±0.18) μm to (2.12±0.47) μm, through the use of different air speeds. It is indicated that the honeycomb formation is humidity-, solvent-, concentration-, and substrate-dependent. Moreover, water molecules introduced from "breath figure" intervene in the formation of hydrogen bonds during FF molecular self-assembly, which results in a hydrogen bond configuration transition from antiparallel β sheet to parallel β sheet. Meanwhile, as a result of the higher polarity of water molecules, the FF molecular array is transformed from laminar stacking into a hexagonal structure. These findings not only elucidate the FF molecule self-assembly process, but also strongly support the mechanism of breath figure array formation. Finally, human embryo skin fibroblast (ESF) culture experiments suggest that FF honeycomb scaffolds are an attractive biomaterial for growth of adherent cells with great potential applications in tissue engineering.

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Section: Methodsmentioning

confidence: 99%

Honeycomb Self‐Assembled Peptide Scaffolds by the Breath Figure Method

Zhu

Yan

et al. 2011

Chemistry A European J

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“…The synthesis of the BCD ring is summarized in Scheme . Coupling of ( S )‐ N ‐methyl‐4‐fluoro‐3‐nitrophenylalanine methyl ester ( 7 )16 with ( R )‐ N ‐Boc‐3,5‐dichloro‐4‐hydroxyphenylglycine ( 8 )17 turned out to be particularly challenging due to the low nucleophilicity of 7 and the high sensitivity of 8 towards epimerization. Under optimized conditions (DEPBT, NaHCO 3 , 0 °C to room temperature), the dipeptide ( 9 ) was isolated in 54 % yield, together with its C C2 epimer (18 %).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Diastereomers of Complestatin and Chloropeptin I: Substrate‐Dependent Atropstereoselectivity of the Intramolecular Suzuki–Miyaura Reaction

Jia

Bois‐Choussy

2008

Angewandte Chemie

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Complestatin (1) [1] and chloropeptin I (2), [2] isolated from Streptomyces lavendulae and Streptomyces sp. WK-3419, respectively, display potent activities against HIV-1-induced cytopathicity and syncyctium formation in CD-4 lymphocytes and inhibit HIV replication by inhibition of gp120-CD-4 binding at a low-micromolar level (IC 50 = 3.3 and 2.0 mm, respectively).[3] The absolute configurations of the amino acid constituents of 1 [4] and 2 [5] were elucidated through detailed NMR, computational, and degradation studies. Complestatin and chloropeptin differ only in the position of the phenylindole ring junction, and it has been demonstrated that the former is readily isomerized to the latter under mildly acidic conditions.[6] These compounds belong to a growing family of vancomycin-type polymacrocyclopeptides with unusual endo aryl-aryl ether and endo biaryl linkages.[7] The presence of racemization-prone chlorinated arylglycines and the inherent difficulties associated with the construction of strained macrocycles made the synthesis of these natural products highly challenging. Although a number of groups have been involved in the total-synthesis exercises, [8] only the group of Snapper and Hoveyda has accomplished the total synthesis of chloropeptin I (2) [9] and an atropisomer of complestatin named isocomplestatin (3; Scheme 1).[10] These total syntheses have also allowed Snapper, Hoveyda, and co-workers to assign the aR configuration to the axial chirality of natural products 1 and 2.We have been interested in this type of natural product [11,12] and have recently reported an atropselective synthesis of the DEFG ring of complestatin by way of an intramolecular Suzuki-Miyaura reaction.[13] As a continuation of this work, we describe herein the syntheses of two atropisomers of the natural products, isocomplestatin (3) and isochloropeptin (5), as well as two other C C2 epimers, 4 and 6 (Scheme 1). The intramolecular S N Ar [14] and SuzukiMiyaura [15] reactions are the two key steps used for the construction of macrocycles BCD and DEF, respectively. We observe that the atropselectivity in the formation of the DEF ring is highly sensitive to both the aryl-aryl bond connectivity and the stereogenicity of the amino acid constituents. A change in the absolute configuration of amino acid C invariably switches the sense of atropselectivity of the subsequent biaryl-forming process.The synthesis of the BCD ring is summarized in Scheme 2. Coupling of (S)-N-methyl-4-fluoro-3-nitrophenylalanine methyl ester (7) [16] with (R)-N-Boc-3,5-dichloro-4-hydroxyphenylglycine (8) [17] turned out to be particularly challenging due to the low nucleophilicity of 7 and the high sensitivity of 8 towards epimerization. Under optimized conditions (DEPBT, NaHCO 3 , 08C to room temperature), the dipeptide (9) was isolated in 54 % yield, together with its C C2 epimer (18 %). Fortuitously, the desired dipeptide 9 can be purified from a mixture of diastereomers by crystallization in a solution of CH 2 Cl 2 /heptane, and the stereochemical integ...

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“…Unfortunately, the benzyloxycarbonyl protective group of flavin 7-Cbz could not be removed by any of the usual methods. [48,49] Cleavage of the trifluoroacetamide 7-TFA in a strongly acidic environment [50] led to the quantitative formation of aminoglycol flavin 7·HCl.…”

Section: Introductionmentioning

confidence: 99%

Thiourea‐Enhanced Flavin Photooxidation of Benzyl Alcohol

Svoboda

Schmaderer

König

2008

Chemistry A European J

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Upon irradiation, flavin oxidises 4-methoxybenzyl alcohol to the corresponding aldehyde using aerial O(2) as the terminal oxidant. We have observed that this reaction is significantly accelerated by the presence of thiourea. A series of thiourea-functionalised flavins has been prepared from flavin isothiocyanates and their photocatalytic efficiencies have been monitored by NMR. The alcohol photooxidation proceeds rapidly and cleanly with high turnover numbers of up to 580, exceeding previously reported performances. A likely mechanistic rationale for the more than 30-fold acceleration of the photo-redox reaction by thiourea has been derived from spectroscopic, electrochemical, and kinetic studies. Thus, thiourea acts as an electron-transfer mediator for the initial photooxidation of 4-methoxybenzyl alcohol by the excited flavins. This mechanism has similarities to electron-relay mechanisms in flavoenzymes, for which cysteine sulfenic acid intermediates are proposed. The observation that thiourea mediates flavin photo-redox processes is valuable for the design of more sophisticated photocatalysts based on Nature's best redox chromophore.

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Chemoenzymatic synthesis of enantiomerically pure 4-fluoro-3-nitro and 3-fluoro-4-nitro phenylalanine

Cited by 33 publications

References 32 publications

Honeycomb Self‐Assembled Peptide Scaffolds by the Breath Figure Method

Honeycomb Self‐Assembled Peptide Scaffolds by the Breath Figure Method

Synthesis of Diastereomers of Complestatin and Chloropeptin I: Substrate‐Dependent Atropstereoselectivity of the Intramolecular Suzuki–Miyaura Reaction

Thiourea‐Enhanced Flavin Photooxidation of Benzyl Alcohol

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