- Antifungal dipeptides incorporating an inhibitor of homoserine dehydrogenase
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The antifungal activity of 5-hydroxy-4-oxo-l-norvaline (HONV), exhibited under conditions mimicking human serum, may be improved upon incorporation of this amino acid into a dipeptide structure. Several HONV-containing dipeptides inhibited growth of human pathogenic yeasts of the Candida genus in the RPMI-1640 medium, with minimal inhibitory concentration values in the 32 to 64?μg?mL?1 range. This activity was not affected by multidrug resistance that is caused by overexpression of genes encoding drug efflux proteins. The mechanism of antifungal action of HONV dipeptides involved uptake by the oligopeptide transport system, subsequent intracellular cleavage by cytosolic peptidases, and inhibition of homoserine dehydrogenase by the released HONV. The relative transport rates determined the anticandidal activity of HONV dipeptides.
- Skwarecki, Andrzej S.,Schielmann, Marta,Martynow, Dorota,Kawczyński, Marcin,Wi?niewska, Aleksandra,Milewska, Maria J.,Milewski, S?awomir
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- A direct route to 2,2,5-trisubstituted pyrrolidines of relevance to kaitocephalin
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2,2,5-Trisubstituted pyrrolidines of relevance to the core of kaitocephalin are readily available by an oxime ring closure using substrates derived from aspartic acid.
- Chandan, Nandkishkor,Moloney, Mark G.
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supporting information
p. 1987 - 1990
(2013/04/10)
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- A microwave-assisted synthesis of (S)-N-protected homoserine γ-lactones from l-aspartic acid
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A three-pot preparation of (S)-N-protected homoserine γ-lactones is presented. Conversion of N-protected l-aspartic acid to an oxazolidinone is followed by selective reduction/acid-catalyzed cyclization to deliver the lactones. Microwave irradiation proved valuable for improving the latter reaction steps in some cases.
- Singh, Suneel P.,Michaelides, Alex,Merrill, A. Rod,Schwan, Adrian L.
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experimental part
p. 6825 - 6831
(2011/10/08)
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- Total synthesis of tryprostatins A and B
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Three distinct synthetic routes to the 2-prenyl tryptophan core skeleton of tryprostatins and their total syntheses are described. The strategies include a traditional gramine-mediated coupling reaction, Fuerstner indole synthesis, and our radical-mediated indole synthesis from o-alkenylphenyl isocyanide. The establishment of reliable conditions for the radical-mediated construction of indoles via a low-temperature radical initiator V-70 (2,2′-azobis(4- methoxy-2,4-dimethylvaleronitrile)) led to the highly efficient syntheses of tryprostatins A and B.
- Yamakawa, Takayuki,Ideue, Eiji,Iwaki, Yuzo,Sato, Ayumu,Tokuyama, Hidetoshi,Shimokawa, Jun,Fukuyama, Tohru
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scheme or table
p. 6547 - 6560
(2011/09/20)
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- Effective methods for the synthesis of N-methyl β-amino acids from all twenty common α-amino acids using 1,3-oxazolidin-5-ones and 1,3-oxazinan-6-ones
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N-Methyl β-amino acids are generally required for application in the synthesis of potentially bioactive modified peptides and other oligomers. Previous work highlighted the reductive cleavage of 1,3-oxazolidin-5-ones to synthesise N-methyl α-amino acids. Starting from α-amino acids, two approaches were used to prepare the corresponding N-methyl β-amino acids. First, α-amino acids were converted to N-methyl α-amino acids by the so-called '1,3-oxazolidin-5-one strategy', and these were then homologated by the Arndt-Eistert procedure to afford N-protected N-methyl β-amino acids derived from the 20 common α-amino acids. These compounds were prepared in yields of 23-57% (relative to N-methyl α-amino acid). In a second approach, twelve N-protected α-amino acids could be directly homologated by the Arndt-Eistert procedure, and the resulting β-amino acids were converted to the 1,3-oxazinan-6-ones in 30-45% yield. Finally, reductive cleavage afforded the desired N-methyl β-amino acids in 41-63% yield. One sterically congested β-amino acid, 3-methyl-3-aminobutanoic acid, did give a high yield (95%) of the 1,3-oxazinan-6-one (65), and subsequent reductive cleavage gave the corresponding AIBN-derived N-methyl β-amino acid 61 in 71% yield (Scheme 2). Thus, our protocols allow the ready preparation of all N-methyl β-amino acids derived from the 20 proteinogenic α-amino acids.
- Hughes, Andrew B.,Sleebs, Brad E.
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p. 2611 - 2637
(2007/10/03)
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- Chemistry and X-ray crystallographic structure of N-protected (5-oxo-1,3-oxazolidin-4-yl)acetic acids: Versatile intermediates in the synthesis of peptidomimetics
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The X-ray crystal structures of [(2′R,4′S)-3′-benzoyl-4′-benzyl-5′-oxo-2′- phenyloxazolidin-4′-yl]acetic acid 16 and [(2′S,4′R)-3′-acetyl-4′-benzyl-5′-oxo-2′- phenyloxazolidin-4′-yl]acetic acid 19 have been determined and their conformations compared to those of related oxazolidinones. Compounds of the type 16 and 19 have also been shown to be useful precursors to succinimide-based peptidomimetics possessing conformational restriction and latent reactivity.
- Abell, Andrew D.,Edwards, Ross A.,Oldham, Mark D.
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p. 1655 - 1662
(2007/10/03)
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- Regioselective amidation of aspartic and glutamic acid
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The synthesis of N-protected aspartic 1-amide and glutamic 1-amide from aspartic and glutamic acids via regioselective amidation of intermediate 5-oxazolidinone derivatives with aqueous ammonia or amine is described.
- Lee,Kim,Ko,Kim
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p. 935 - 936
(2007/10/02)
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- Synthesis of N-(tert-Butoxycarbonyl)-3-(4-thiazolyl)-L-alanine
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Efficient syntheses of N-(tert-butoxycarbonyl)-3-(4-thiazolyl)-L-alanine (11) are described.
- Hsiao, Chi-Nung,Leanna, M. Robert,Bhagavatula, Lakshmi,Lara, Edvin De,Zydowsky, Thomas M.,et al.
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p. 3507 - 3517
(2007/10/02)
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- A Convenient Differential Protection Strategy for Functional Group Manipulation of Aspartic and Glutamic Acids
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Procedures are provided for selective protection of the α-carboxyl groups of aspartic and glutamic acids via the 5-oxazolidinones 2.A convenient synthesis of a differentially protected derivative of (S)-2,3-diaminopropanoic acid, 3, is described, along wi
- Scholtz, John M.,Bartlett, Paul A.
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p. 542 - 544
(2007/10/02)
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- SYNTHESIS OF BICYCLIC γ-LACTAMS VIA OXAZOLIDINONES
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Oxazolidinone aldehyde 10 reacts with L-cysteine methyl ester to produce N-hydroxymethyl bicyclic γ-lactam 11 in a double cyclisation reaction.With D-cysteine methyl ester, an epimeric mixture of N-hydroxymethyl bicyclic γ-lactams 12 is obtained.Bicyclic
- Baldwin, Jack E.,Lee, E.
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p. 6551 - 6554
(2007/10/02)
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- Synthesis of N2-Protected L-2,3-Diaminopropanoic Acids
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The title compounds have been synthesized from N-protected L-aspartic acid via Curtis rearrangement.
- Noguchi, Noriyoshi,Kuroda, Tsuyoshi,Hatanaka, Minoru,Ishimaru, Toshiyasu
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p. 633 - 634
(2007/10/02)
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