Enantiospecific synthesis of α-amino acid semialdehydes: a key step for the synthesis of unnatural unsaturated and saturated α-amino acids

Padrón, José M.; Kokotos, George; Martı́n, Tomás; Markidis, Theodoros; Gibbons, William A.; Martı́n, Victor S.

doi:10.1016/s0957-4166(98)00354-1

Cited by 94 publications

(70 citation statements)

References 23 publications

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“…Just as the pioneering synthetic work of Sir John Cornforth enabled the careful investigation of the mechanisms of enzyme catalysis, the programmed construction of homogeneous peptide and protein targets using the tools afforded by chemical synthesis will no doubt prove an invaluable resource for understanding the intricate relationship between protein structure and function. Madanin-1 (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) Madanin-1 (49-60)…”

Section: Discussionmentioning

confidence: 99%

“…Madanin-1 (1-27) Chimadanin (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) Chimadanin Chimadanin (1-19)…”

Section: Discussionmentioning

confidence: 99%

“…[31] A subsequent base-catalyzed Henry reaction between aldehyde 31 and MeNO 2 in the presence of tetra-n-butylammonium fluoride (TBAF) afforded the nitro alcohol 32 as a 1 : 1 mixture of diastereomers. Rather than installing the key thiol auxiliary at this point through an activation-displacement protocol, the authors opted instead to proceed through the formation of Michael acceptor 33, which was generated in a one-pot acetylation-elimination protocol in the presence of acetic anhydride and 4-dimethylaminopyridine (DMAP).…”

Section: Synthesis Of Thiol-derived Amino Acids Through Nucleophilic mentioning

confidence: 99%

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Synthetic Amino Acids for Applications in Peptide Ligation–Desulfurization Chemistry

Malins

Payne

2015

Aust. J. Chem.

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Native chemical ligation is a powerful tool for the convergent assembly of homogeneous peptide and protein targets from unprotected peptide fragments. The method involves the chemoselective coupling of a peptide thioester with a peptide bearing an N-terminal cysteine (Cys) residue and is mediated by the nucleophilic Cys thiol functionality. A widely adopted extension of the technique for the disconnection of protein targets at alanine (Ala) ligation junctions has been the application of post-ligation desulfurization protocols for the mild removal of the Cys thiol moiety. Recently, attention has turned to the construction of synthetic amino acid building blocks bearing suitably positioned b-, g-, or d-thiol ligation auxiliaries with a view to expanding the scope of the ligation-desulfurization manifold. To date, several thiol-derived amino acids have been prepared, greatly increasing the generality and flexibility of chemoselective ligation technologies for the chemical synthesis of diverse protein targets. This review will highlight the current synthetic approaches to these important amino acid building blocks.

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Section: Discussionmentioning

confidence: 99%

“…Madanin-1 (1-27) Chimadanin (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) Chimadanin Chimadanin (1-19)…”

Section: Discussionmentioning

confidence: 99%

Section: Synthesis Of Thiol-derived Amino Acids Through Nucleophilic mentioning

confidence: 99%

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Synthetic Amino Acids for Applications in Peptide Ligation–Desulfurization Chemistry

Malins

Payne

2015

Aust. J. Chem.

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“…The latter could be obtained by selective reduction of L-malic acid at C4 (Scheme 1, strategy 1a). Since this selective reduction of malic acid was not successful, we tried the method by Padron et al 10 , to selectively reduce the di-Boc protected aspartic acid to the corresponding C4 semialdehyde (Scheme 1, strategy 1b). Indeed, the selective reduction starting from aspartic acid proceeded smoothly with a 67% yield.…”

Section: Nih Public Accessmentioning

confidence: 99%

Modular Strategies for Structure and Function Employed by Marine Cyanobacteria: Characterization and Synthesis of Pitinoic Acids

Montaser¹,

Paul²,

Luesch³

2013

Planta Med

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Novel bioactive lipids were identified from a Guamanian cyanobacterium; the Pseudomonas aeruginosa quorum sensing inhibitor pitinoic acid A (1) and the anti-inflammatory pitinoic acids B (2) and C. The structure of 2 was confirmed by synthesis, which also allowed for biological evaluation. Since 2 is an ester of pitinoic acids A and C, it represents a prodrug strategy to liberate dual biological activity for the management of P. aeruginosa infections and their associated inflammation.Pseudomonas aeruginosa is a Gram-negative bacterium that causes opportunistic infections in different host tissues and organs. For example, cystic fibrosis (CF) infections and microbial keratitis (MK) are two of the most serious lung and eye infections, respectively, caused by this organism. 1, 2 Bacterial quorum sensing (QS) has been shown to play a major role in bacterial pathogenesis, where the infection and tissue destruction are facilitated by several QS-regulated virulence factors including elastase (LasB) and the pigment pyocyanin. 2,3 Tissue damage is also aggravated by the host's defense response, where the release of pro-inflammatory mediators and the prolonged inflammatory response are other contributors to tissue pathology. 2, 4-8 Accordingly, inhibiting QS pathways in P. aeruginosa and simultaneously controlling the associated inflammatory response is a promising strategy for the treatment of infections caused by this organism.luesch@cop.ufl.edu. Supporting Information Available. 1D and 2D NMR spectra for compounds 1 and 2, supporting figures including spectral data and characterization of synthetic intermediates, experimental procedures and additional RT-qPCR data. This material is available free of charge via the Internet at http://pubs.acs.org. During our efforts to discover novel bioactive compounds from marine cyanobacteria, we explored a population of a marine cyanobacterium morphologically similar to Lyngbya sp. NIH Public Accesscollected from a channel at the north end of Piti Bay at Guam, through NMR-guided fractionation. We isolated and characterized the novel lipids pitinoic acid A (1) (5-methylene decanoic acid) and its chlorinated ester, pitinoic acid B (2). The fatty acid 1 inhibits QS in P. aeruginosa, while the ester 2 prevents the induction of pro-inflammatory cytokine expression in LPS-induced THP-1 macrophages. In addition, we were able to identify the presence of pitinoic acid C, the alcohol moiety in 2, in one HPLC-fraction, which also maintained the anti-inflammatory effect detected for 2. Based on this, 2 appears to be a nature-designed prodrug which could deliver two essential moieties with different bioactivities upon hydrolysis; the QS-inhibitory module pitinoic acid A (1) and the antiinflammatory module pitinoic acid C.The EtOAc-MeOH extract was subjected to solvent-solvent partitioning followed by fractionation using silica gel chromatography. 1 H NMR profiles of the generated silica fractions showed a major simple fatty acid (1) HPLC purification of another silica fraction that elut...

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“…The synthesis of modified lysine started from commercially available l-glutamic acid, which was converted into aldehyde 1 in three steps according to a previously reported procedure (Scheme 2). [18] Subsequently, the Henry reaction was applied to 1 with nitromethane, in the presence of TBAF as a base, to give a diastereomeric mixture of nitro alcohol 2 in a 1:1 ratio (based on 1 H NMR spectroscopy; see the Supporting Information). The one-pot acetylation, followed by elimination of the alcohol functionality on the nitro alcohol 2 using acetic anhydride and 4-dimethylaminopyridine, afforded the E/Z mixture of the Michael acceptor 3 in 71 % yield.…”

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confidence: 99%

Highly Efficient and Chemoselective Peptide Ubiquitylation

et al. 2009

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Enantiospecific synthesis of α-amino acid semialdehydes: a key step for the synthesis of unnatural unsaturated and saturated α-amino acids

Cited by 94 publications

References 23 publications

Synthetic Amino Acids for Applications in Peptide Ligation–Desulfurization Chemistry

Synthetic Amino Acids for Applications in Peptide Ligation–Desulfurization Chemistry

Modular Strategies for Structure and Function Employed by Marine Cyanobacteria: Characterization and Synthesis of Pitinoic Acids

Highly Efficient and Chemoselective Peptide Ubiquitylation

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