Effective synthesis of kynurenine-containing peptides via on-resin ozonolysis of tryptophan residues: synthesis of cyclomontanin B

Wong, Chi‐Ming; Lam, Hiu Yung; Li, Xuechen

doi:10.1039/c3ob41631c

Cited by 50 publications

(29 citation statements)

References 23 publications

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“…An alternative synthetic route towards daptomycin ( 1 ) was devised to circumvent the direct esterification of the Kyn building block. Inspired by the effective synthesis of Kyn‐containing peptide cyclomontanin B via on‐resin ozonolysis of the corresponding Trp residue to a Kyn residue (Scheme ), and a previous report on the high efficiency of the esterification reaction between Fmoc‐Trp(Boc)‐OH and a resin‐bound threonine‐containing decapeptide, we adopted this combined strategy for the solid‐phase synthesis of native daptomycin ( 1 ) (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

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A Versatile Boc Solid Phase Synthesis of Daptomycin and Analogues Using Site Specific, On‐Resin Ozonolysis to Install the Kynurenine Residue

Hermant

Yang

et al. 2019

Chemistry A European J

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Ad en ovo solid-phase synthesis of the cyclic lipodepsipeptide daptomycin via Boc chemistry was achieved. The challenging ester bond formation between the nonproteinogenic amino acid kynurenine was achieved by esterification of at hreonine residue with ap rotected tryptophan. Subsequent late-stage on-resin ozonolysis, inspired by the biomimetic pathway,a fforded the kynurenine residue directly.S ynthetic daptomycin possessed potent antimicrobiala c-tivity (MIC 100 = 1.0 mgmL À1 )a gainst S. aureus,w hile five other daptomycin analogues containing (2R,3R)-3-methylglutamic acid, (2S,4S)-4-methylglutamic acid or canonical glutamic acid at position twelve prepared using this new methodology were all inactive, clearly establishing that the (2S,3R)-3methylglutamic acid plays ak ey role in the antimicrobial activity of daptomycin.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.

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Section: Resultsmentioning

confidence: 99%

“…AA = amino acid. [24] Scheme4.Synthesis of daptomycin (1)and Dapt-(2R,3R)-MeGlu analogue 16. the reaction mixture (TableS1, entry 1, see Supporting Information). This was not as urprisingr esult as ester bonds in depsipeptides are susceptible to basic conditions.…”

Section: Synthesis Of Daptomycin(1)mentioning

confidence: 99%

A Versatile Boc Solid Phase Synthesis of Daptomycin and Analogues Using Site Specific, On‐Resin Ozonolysis to Install the Kynurenine Residue

Hermant

Yang

et al. 2019

Chemistry A European J

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“…In addition, STL-mediated peptide cyclization has been used to synthesize daptomycin and other cyclic peptides of various sizes (Lam et al, 2013; Wong et al, 2013a,b; Zhao et al, 2013). More recently, STL has been used in the form of expression protein ligation, producing a RNase-peptiod conjugate (Levine et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Realizing serine/threonine ligation: scope and limitations and mechanistic implication thereof

Wong

Lam

et al. 2014

Front. Chem.

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Serine/Threonine ligation (STL) has emerged as an alternative tool for protein chemical synthesis, bioconjugations as well as macrocyclization of peptides of various sizes. Owning to the high abundance of Ser/Thr residues in natural peptides and proteins, STL is expected to find a wide range of applications in chemical biology research. Herein, we have fully investigated the compatibility of the STL strategy for X-Ser/Thr ligation sites, where X is any of the 20 naturally occurring amino acids. Our studies have shown that 17 amino acids are suitable for ligation, while Asp, Glu, and Lys are not compatible. Among the working 17 C-terminal amino acids, the retarded reaction resulted from the bulky β-branched amino acid (Thr, Val, and Ile) is not seen under the current ligation condition. We have also investigated the chemoselectivity involving the amino group of the internal lysine which may compete with the N-terminal Ser/Thr for reaction with the C-terminal salicylaldehyde (SAL) ester aldehyde group. The result suggested that the free internal amino group does not adversely slow down the ligation rate.

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“…Various cyclic peptides of sizes from 4 to 9 amino acids have been successfully prepared by way of serine/threonine ligation-mediated peptide cyclization [33 ,34 ]. As such, several natural bioactive cyclic peptides have been synthesized, including cyclomontanin B [38], yunnanin C [29], mahafacyclin B [34 ] and daptomycin [39] (Scheme 4). The cyclization proceeded smoothly, even in the presence of the unprotected lysine residue.…”

Section: Synthesis Of the Requisite Peptide Sal Estermentioning

confidence: 99%

Serine/threonine ligation for the chemical synthesis of proteins

Lee

2014

Current Opinion in Chemical Biology

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Effective synthesis of kynurenine-containing peptides via on-resin ozonolysis of tryptophan residues: synthesis of cyclomontanin B

Cited by 50 publications

References 23 publications

A Versatile Boc Solid Phase Synthesis of Daptomycin and Analogues Using Site Specific, On‐Resin Ozonolysis to Install the Kynurenine Residue

A Versatile Boc Solid Phase Synthesis of Daptomycin and Analogues Using Site Specific, On‐Resin Ozonolysis to Install the Kynurenine Residue

Realizing serine/threonine ligation: scope and limitations and mechanistic implication thereof

Serine/threonine ligation for the chemical synthesis of proteins

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