- Biocatalytic synthesis of valaciclovir using commercial enzymes
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Proof-of-concept has been demonstrated for the biocatalytic transformation of aciclovir into valaciclovir, attaining high conversions from a solid-to-solid biotransformation in l-valine methyl ester using various formulations of Subtilisin Carlsberg activated for use in organic solvent.
- McClean, Kathleen,Preston, Christopher,Spence, David,Sutton, Peter W.,Whittall, John
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- L-valine and L-proline - solid-state IR-LD spectroscopic study
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Spectral investigation including IR-characteristic bands assignment of the amino acids zwitterions L-Valine (L-Val) and L-Proline (L-Pro) was carried out by linear-dichroic infrared (IR-LD) spectroscopy of oriented solid sample as a nematic liquid crystal suspension. The obtained experimental IR-LD results (transition moment directions) were compared with known crystal X-ray data for molecules orientation in the unit cells of the studied compounds, confirming the applicability of the used spectral method for structural determination. The influence of the protonation on the IR-spectroscopic patterns of the both amino acids is discussed.
- Chapkanov,Zareva
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- An enantioselective synthesis of (S)-4-fluorohistidine
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We report a new synthesis of enantiomerically pure (S)-4-fluorohisitidine based on diastereoselective alkylation of MOM-protected 4-fluoro-5-bromomethyl imidazole using the Sch?llkopf bis-lactim amino acid synthesis. Improvements in procedures for preparation of key intermediates are also described. (S)-4-Fluorohisitidine prepared by this new method was identical in all respects to material prepared by previous procedures.
- Hajduch, Jan,Cramer, John C.,Kirk, Kenneth L.
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- Preparation of Constrained Unnatural Aromatic Amino Acids via Unsaturated Diketopiperazine Intermediate
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Unnatural aromatic amino acids are useful tools in drug discovery, since their insertion in bioactive peptide sequences can change the side chains spatial orientation, the backbone conformation and above all, their bioactivity. In this communication, we propose a straightforward method to synthesize 2′,6′-dimethyl-tyrosine and 2′,6′-dimehylphenyl-alanine derivatives as handling building blocks for peptide synthesis via unsaturated diketopiperazine (DKP) intermediate.
- Mollica, Adriano,Costante, Roberto,Mirzaie, Sako,Carradori, Simone,Macedonio, Giorgia,Stefanucci, Azzurra,Novellino, Ettore
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p. 2106 - 2110
(2016/11/23)
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- Cycloforskamide, a cytotoxic macrocyclic peptide from the sea slug Pleurobranchus forskalii
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A macrocylic dodecapeptide, cycloforskamide, was isolated from the sea slug Pleurobranchus forskalii, collected off Ishigaki Island, Japan. Its planar structure was deduced by extensive NMR analyses and was further confirmed by MS/MS fragmentation analyses. Finally, the absolute configuration was determined by total hydrolysis and chiral-phase gas chromatographic analysis. This novel dodecapeptide contains three d-amino acids and three thiazoline heterocycles and exhibits cytotoxicity against murine leukemia P388 cells, with an IC 50 of 5.8 μM.
- Tan, Karen Co,Wakimoto, Toshiyuki,Takada, Kentaro,Ohtsuki, Takashi,Uchiyama, Nahoko,Goda, Yukihiro,Abe, Ikuro
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p. 1388 - 1391
(2013/08/23)
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- Tumescenamide C, an antimicrobial cyclic lipodepsipeptide from Streptomyces sp.
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Tumescenamide C, a new cyclic lipodepsipeptide, was isolated from a culture broth of an actinomycete Streptomyces sp. KUSC-F05. Tumescenamide C was a congener of tumescenamides A and B, representing a sixteen-membered ring system, consisting of two proteinogenic and three non-proteinogenic amino acids, to which a methyl-branched fatty acid was attached. The planar structure was determined by spectroscopic analysis, while its absolute stereochemistry was determined by chemical degradation and asymmetric synthesis. Tumescenamide C exhibited antimicrobial activity with high selectivity against Streptomyces species.
- Kishimoto, Shinji,Tsunematsu, Yuta,Nishimura, Shinichi,Hayashi, Yutaka,Hattori, Akira,Kakeya, Hideaki
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experimental part
p. 5572 - 5578
(2012/09/08)
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- Isolation and structural determination of the antifouling diketopiperazines from marine-derived Streptomyces praecox 291-11
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Marine derived actinomycetes constituting 185 strains were screened for their antifouling activity against the marine seaweed, Ulva pertusa, and fouling diatom, Navicula annexa. Strain 291-11 isolated from the seaweed, Undaria pinnatifida, rhizosphere showed the highest antifouling activity and was identified as Streptomyces praecox based on a 16S rDNA sequence analysis. Strain 291-11 was therefore named S. praecox 291-11. The antifouling compounds from S. praecox 291-11 were isolated, and their structures were analyzed. The chemical constituents representing the antifouling activity were identified as (6S,3S)-6-benzyl-3-methyl-2,5-diketopiperazine (bmDKP) and (6S,3S)-6-isobutyl-3- methyl-2,5-diketopiperazine (imDKP) by interpreting the nuclear magnetic resonance and high-resolution mass spectroscopy data. Approximately 4.8mg of bmDKP and 3.1 mg of imDKP were isolated from 1.2 g of the S. praecox 291-11 crude extract. Eight different compositions of culture media were investigated for culture, the TBFeC medium being best for bmDKP and TCGC being the optimum for imDKP production. Two compounds respectively showed a 17.7 and 21 therapeutic ratio (LC50/EC50) to inhibit zoospores, and two compounds respectively showed a 263 and 120.2 therapeutic ratio to inhibit diatoms.
- Cho, Ji Young,Kang, Ji Young,Hong, Yong Ki,Baek, Hyo Hyun,Shin, Hyoun Woong,Kim, Myoung Sug
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experimental part
p. 1116 - 1121
(2012/10/07)
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- A phenylacetylated peptide, JBIR-96, isolated from Streptomyces sp. RI051-SDHV6
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Searching for metabolites from Streptomyces sp. RI051-SDHV6 resulted in the discovery of a novel peptide, JBIR-96 (1). The structure of 1 was established as an N-phenylacetylated pentapeptide involving a cysteic acid and a peptide lactone structure by extensive NMR and MS analyses. In addition, the absolute configuration of 1 was established by Marfey's and modified Mosher's methods. (Chemical Equation Presented).
- Ueda, Jun-Ya,Izumikawa, Miho,Kozone, Ikuko,Yamamura, Hideki,Hayakawa, Masayuki,Takagi, Motoki,Shin-Ya, Kazuo
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experimental part
p. 1344 - 1347
(2011/07/29)
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- Hydration of amino acids from ultrasonic measurements
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In this paper the results of compressibility of aqueous solutions of amino acids in water and in aqueous HCl and NaOH solutions at 25 °C are presented. The effect of the charged protonated amino groups and deprotonated carboxylic groups on the hydration number was tested. The idea of additivity of the hydration number with the constituents of the solute molecule was successfully applied and discussed.
- Burakowski, Andrzej,Gliński, Jacek
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experimental part
p. 12157 - 12161
(2011/01/11)
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- Diastereoselective synthesis of quaternary α-amino acids from diketopiperazine templates
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Sequential enolate alkylations of (S)-N(1)-methyl-5-methoxy-6-isopropyl-3, 6-dihydropyrazin-2-one and (S)-N(1)-p-methoxybenzyl-5-methoxy-6-isopropyl-3,6- dihydropyrazin-2-one proceed with excellent levels of diastereoselectivity (>90% de) affording quaternary α-amino acids in high enantiomeric excess (>98% ee) after deprotection and hydrolysis. This journal is The Royal Society of Chemistry.
- Davies, Stephen G.,Christopher Garner,Ouzman, Jaqueline V. A.,Roberts, Paul M.,Smith, Andrew D.,Snow, Emma J.,Thomson, James E.,Tamayo, Juan A.,Vickers, Richard J.
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p. 2138 - 2147
(2008/03/14)
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- Asymmetric conjugate reductions with samarium diiodide: Asymmetric synthesis of (2S,3R)- And (2S,3S)-[2-2H,3-2H]-leucine-(S)- phenylalanine dipeptides and (2S,3R)-[2-2H,3-2H]- phenylalanine methyl ester
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The highly diastereoselective samarium diiodide and D2O-promoted conjugate reduction of homochiral (E)- and (Z)-benzylidene and isobutylidene diketopiperazines (E)-5,7 and (Z)-6,8 has been demonstrated. This methodology allows the asymmetric synthesis of methyl (2S,3R)-dideuteriophenylalanine 27 in ≥95% de and >98% ee, and (2S,3R)- or (2S,3S)-dideuterioleucine-(S)- phenylalanine dipeptides 37 and 38 in moderate de, 66% and 74% respectively. A mechanism is proposed to account for this process. The Royal Society of Chemistry 2005.
- Davies, Stephen G.,Rodriguez-Solla, Humberto,Tamayo, Juan A.,Cowley, Andrew R.,Concellon, Carmen,Garner, A. Christopher,Parkes, Alastair L.,Smith, Andrew D.
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p. 1435 - 1447
(2007/10/03)
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- Resolution of DL-racemic mixtures
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The present invention relates to a process for the resolution of DL-racemic mixtures of compounds which crystalize in the form of a conglumerate. Both, the D and L-enantiomers are obtained according to the invention in a industrially feasable process by adding chiral enantioselective polymers to the supersaturated solution of the racemat to inhibit crystalization of one enantiomer. Next a DL-racemic mixture of said compound is suspended in about twice the amount of the crystallized enantiomer. Consequently, the opposite enantiomer could be recovered by said suspension by physical separation.
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Page column 7-8
(2008/06/13)
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- Asymmetric synthesis of substituted 1-aminocyclopropane1-carboxylic acids via diketopiperazine methodology
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Diketopiperazinespirocyclopropane 12 is prepared in > 98% d.e. via the conjugate addition of a phosphorus ylide to (6S)-N, N′-bis(p-methoxybenzyl)-3-methylenepiperazine-2,5-dione 2. Deprotection and hydrolysis of adduct 12 and subsequent peptide coupling demonstrate the applicability of this methodology to the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids for incorporation into novel peptides. A model for the high level of diastereofacial selectivity observed in the cyclopropanation reaction is presented. A highly selective asymmetric approach (> 98% d.e.) to (S)-[2,2-2H 2]-1-aminocyclopropane-l-carboxylic acid 29 is also reported via a deuterated sulfur ylide addition to acceptor 2.
- Bunuel, Elena,Bull, Steven D.,Davies, Stephen G.,Garner, A. Christopher,Savory, Edward D.,Smith, Andrew D.,Vickers, Richard J.,Watkin, David J.
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p. 2531 - 2542
(2007/10/03)
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- Preparation and Characterization of [5-13C]-(2S,4R)-Leucine and [4-13C]-(2S,3S)-Valine - Establishing Synthetic Schemes to Prepare Any Site-Directed Isotopomer of L-Leucine, L-Isoleucine and L-Valine
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In this paper a chemo-enzymatic method has been developed that gives access to any isotopomer of the essential amino acids isoleucine and valine. The method gives the correct introduction of the second chiral center in (2S,3S)-isoleucine and allows for discrimination between the two prochiral methyl groups in valine as shown by the preparation of (2S,3S)-[4- 13C] valine. For the preparation of (2S)-leucine in any isotopomeric form, the O'Donnell method to prepare optically active amino acids has been used. The protected glycine scaffold used in this method has been prepared by a strategy that allows access to any isotopomeric form. The preparation of [5-13C]-(2S,4R)-leucine shows that the O'Donnell method in combination with the Evans method to obtain chiral 2-methylpropyl iodide leads to a good discrimination between the two prochiral methyl groups. The O'Donnell strategy for the preparation of α-amino acids is preferred over other methods since the reaction conditions are mild, the chiral auxiliary can be easily recovered and the optically active product can be easily separated. For the preparation of isotopically enriched valine and isoleucine the O'Donnell method is not suitable, because the alkyl substituents involved have a secondary halide substituent which is sterically too hindered to give an effective reaction with the protected glycine. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Siebum, Arjan H. G.,Woo, Wei Sein,Lugtenburg, Johan
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p. 4664 - 4678
(2007/10/03)
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- Asymmetric synthesis of (2R,5R)-2,5-diaminohexan-1,6-dioic acid
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Schollkopf's auxiliary 16 was added to bis-lactim iodide 21 to give 1,2- bis[(3S,6R)-3,6-dihydro-2,5-dimethoxy-3-isopropylpyrazin-6-yl]ethane 22 in 50% d.e. Dimer 22 was separated from its diastereoisomer 23 and deprotected using 6M HCl to afford homochiral (2R,5R)-2,5-diaminohexan-1,6-dioic acid 24.
- Bull, Steven D.,Chernega, Alexander N.,Davies, Stephen G.,Moss, William O.,Parkin, Richard M.
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p. 10379 - 10388
(2007/10/03)
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- Asymmetric Synthesis Catalyzed by Chiral Ferrocenylphosphine-Transition-Metal Complexes. 8. Palladium-Catalyzed Asymmetric Allylic Amination
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Chiral ferrocenylphosphine ligands, represented by (R)-N-methyl-N--1-ethylamine ((R)-(S)-1a), which have a pendant side chain bearing a hydroxy group at the terminal position, were designed and used successfully for palladium-catalyzed asymmetric allylic amination of allylic substrates containing a 1,3-disubstituted propenyl structure (RCH=CHCH(X)R: R = Ph, Me, n-Pr, i-Pr; X = OCOOEt, OCOMe, OP(O)Ph2, etc.).Reaction of the allylic substrates with benzylamine in the presence of a palladium catalyst prepared in situ from Pd2(dba)3 and (R)-(S)-1a gave high yields of amination products (RCH=CHC*H(NHCH2Ph)R: >97percent ee (R) for R = Ph, 73percent ee (S) for R = Me, 82percent ee (S) for R = n-Pr, and 97percent ee (S) for R = i-Pr).The allylamines were converted into optically active amino acids and their derivatives.The high stereoselectivity of the ferrocenylphosphine ligand is expected to be caused by an attractive interaction between the terminal hydroxy group on the ligand and the incoming amine, which directs the nucleophilic attack on one of the ?-allyl carbons.The key role of the hydroxy group was supported by an X-ray structure analysis of a ?-allylpalladium complex and (31)P NMR studies.It was demonstrated that the pendant side chain on the ferrocenylphosphine ligand is directed toward the reaction site on palladium and the terminal hydroxy group is located at the position close to one of the ?-allyl carbon atoms and that ?-allyl group on the palladium coordinated with the ferrocenylphosphine 1a adopts one of the two possible conformational isomers with high selectivity (20/1) in an equilibrium state.
- Hayashi, Tamio,Yamamoto, Akihiro,Ito, Yoshihiko,Nishioka, Eriko,Miura, Hitoshi,Yanagi, Kazunori
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p. 6301 - 6311
(2007/10/02)
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- A STEREOSELECTIVE SYNTHESIS OF N-BOC-α-AMINO ALCOHOLS AND α-AMINO ACIDS
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A sterteoselective synthesis of N-Boc-α-amino alcohols and α-amino acids via the addition of Grignard reagents to the chiral electrophilic glycine equivalent α-bromo-N-Boc-glycine(-)phenylmenthylester is described.
- Ermert, Philipp,Meyer, Jsabella,Stucki, Christoph,Schneebeli, Joerg,Obrecht, Jean-Pierre
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p. 1265 - 1268
(2007/10/02)
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- CHLOROTRIMETHYLSILANE-PHENOL AS A MILD DEPROTECTION REAGENT FOR THE TERT-BUTYL BASED PROTECTING GROUPS IN PEPTIDE SYNTHESIS
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Efficient deprotection of the tertbutyl urethane group by 1 M Me3SiCl- 1 M and 3 M-phenol reagents is described.
- Kaiser, Emil,Tam, James P.,Kubiak, Teresa M.,Merrifield, R. B.
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p. 303 - 306
(2007/10/02)
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- ENANTIOSELECTIVE SYNTHESES OF α-AMINO ACIDS FROM 10-SULFONAMIDO-ISOBORNYL ESTERS AND DI-t-BUTYL AZODICARBOXYLATE
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Successive treatment of chiral esters 7 with LDA/Me3SiCl and di-t-butyl azodicarboxylate/TiCl4 and Ti(OiPr)4 gave N,N-di-t-butoxycarbonylhydrazinoesters 11 which on deacylation, hydrogenolysis, transesterification and acidic hydrolysis furnished (2S)-α-amino acid hydrochlorides 13 in good overall yields, high enantiomeric purity and with efficient recovery of the alcohol auxiliary 4.Experimental evidence for the configuration and conformation of the intermediate O-silyl ketene acetals 1 is provided.
- Oppolzer, Wolfgang,Moretti, Robert
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p. 5541 - 5552
(2007/10/02)
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- Enantioselective Synthesis of α-Amino Acids from 10-(Aminosulfonyl)-2-bornyl Esters and Di(tert-butyl) Azodicarboxylate
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Successive treatment of chiral esters 1 with LiN(i-Pr)2/Me3SiCl and di(tert-butyl) azodicarboxylate/TiCl4/Ti(i-PrO)4 gave N,N'-dihydrazino esters 9 which on deacylation, hydrogenolysis, transesterification, and acidic hydrolysis furnished (2S)-α-amino acids 6 in high enantiomeric purity with efficient recovery of the auxiliary alcohol 7.
- Oppolzer, Wolfgang,Moretti, Robert
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p. 1923 - 1926
(2007/10/02)
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