- Design, synthesis and functional analysis of dansylated polytheonamide mimic: An artificial peptide ion channel
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We report herein the design, total synthesis, and functional analysis of a novel artificial ion channel molecule, designated as dansylated polytheonamide mimic (3). The channel 3 was designed based on an exceptionally potent cytotoxin, polytheonamide B (1
- Itoh, Hiroaki,Matsuoka, Shigeru,Kreir, Mohamed,Inoue, Masayuki
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- Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
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Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.
- Einsiedler, Manuel,Jamieson, Cooper S.,Maskeri, Mark A.,Houk, Kendall N.,Gulder, Tobias A. M.
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supporting information
p. 8297 - 8302
(2021/03/01)
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- pDobz/pDobb protected diaminodiacid as a novel building block for peptide disulfide-bond mimic synthesis
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The diaminodiacid strategy has been widely studied in the chemical synthesis of peptide disulfide bond mimics. Diaminodiacid building blocks, which are key intermediates, are currently under the spotlight. However, one technical bottleneck inherent in existing building blocks is the contamination problem caused by the heavy metal reagents during the deprotection process, which makes the peptides less suitable for pharmaceutical use. Herein, we describe the successful development of a p-dihydroxyborylbenzyloxycarbonyl pinacol ester (pDobz)- and p-dihydroxyborylbenzyl pinacol ester (pDobb)-based novel diaminodiacid building block that can be easily deprotected via mild treatment with amine oxide. Its efficiency and practicability were also confirmed by the total synthesis of contryphan-Vn disulfide bond mimic. The results suggested that this novel diaminodiacid building block has satisfactory Fmoc SPPS compatibility, yet only required a facile, rapid, and metal-free deprotection process. We believe this novel diaminodiacid building block could promote further development of the diaminodiacid strategy.
- Liu, Chao,Zou, Yan,Hu, Honggang,Jiang, Yunyun,Qin, Luping
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p. 5438 - 5444
(2019/03/02)
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- α-Propargyl amino acid-derived optically active novel substituted polyacetylenes: Synthesis, secondary structures, and responsiveness to ions
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Novel optically active substituted acetylenes HCi￡ CCH 2CR1(CO2CH3)NHR2 [(S)-/(R)-1: R1 = H, R2 = Boc, (S)-2: R1 = CH3, R2 = Boc, (S)-3: R1 = H, R2 = Fmoc, (S)-4: R1 = CH3, R2 = Fmoc (Boc = tert-butoxycarbonyl, Fmoc = 9-fluorenylmethoxycarbonyl)] were synthesized from α-propargylglycine and α-propargylalanine, and polymerized with a rhodium catalyst to provide the polymers with number-average molecular weights of 2400-38,900 in good yields. Polarimetric, circular dichroism (CD), and UV-vis spectroscopic analyses indicated that poly[(S)-1], poly[(R)-1], and poly[(S)-4] formed predominantly one-handed helical structures both in polar and nonpolar solvents. Poly[(S)-1a] carrying unprotected carboxy groups was obtained by alkaline hydrolysis of poly[(S)-1], and poly[(S)-4b] carrying unprotected amino groups was obtained by removal of Fmoc groups of poly[(S)-4] using piperidine. Poly[(S)-1a] and poly[(S)-4b] also exhibited clear CD signals, which were different from those of the precursors, poly[(S)-1] and poly[(S)-4]. The solution-state IR measurement revealed the presence of intramolecular hydrogen bonding between the carbamate groups of poly[(S)-1] and poly[(S)-1a]. The plus CD signal of poly[(S)-1a] turned into minus one on addition of alkali hydroxides and tetrabutylammonium fluoride, accompanying the red-shift of λmax. The degree of λmax shift became large as the size of cation of the additive.
- Sogawa, Hiromitsu,Shiotsuki, Masashi,Sanda, Fumio
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experimental part
p. 2008 - 2018
(2012/07/13)
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- Azide- and alkyne-functionalised α- And β3-amino acids
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The synthesis and full characterisation of bifunctional β3-amino acids that have side chains functionalised with terminal azides (S)-4 and (R)-4 or acetylenes 5 and 6 is reported for the first time. The building blocks incorporate a turn-inducing β3-segment and a side chain that can be functionalised further, for example, through copper-catalysed Huisgen cycloaddition. Moreover, the corresponding α-amino acids 1 and 3 have been synthesised and characterised. All amino acid building blocks were of high optical purity as demonstrated by derivatisation and subsequent NMR analysis.
- Sminia, Tjerk Jacco,Pedersen, Daniel Sejer
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supporting information
p. 2643 - 2646,4
(2012/12/13)
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- Azide- and alkyne-functionalised α- And β3-amino acids
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The synthesis and full characterisation of bifunctional β3-amino acids that have side chains functionalised with terminal azides (S)-4 and (R)-4 or acetylenes 5 and 6 is reported for the first time. The building blocks incorporate a turn-inducing β3-segment and a side chain that can be functionalised further, for example, through copper-catalysed Huisgen cycloaddition. Moreover, the corresponding α-amino acids 1 and 3 have been synthesised and characterised. All amino acid building blocks were of high optical purity as demonstrated by derivatisation and subsequent NMR analysis. Georg Thieme Verlag KG Stuttgart · New York.
- Sminia, Tjerk Jacco,Pedersen, Daniel Sejer
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supporting information
p. 2643 - 2646
(2013/01/15)
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- End-stapled homo and hetero collagen triple helices: A click chemistry approach
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A CuAAC reaction was established for modular synthesis of end-stapled homo- and hetero-triple helical peptides, generating "clicked" macro-assemblies with enhanced thermal stability.
- Byrne, Cillian,McEwan, Paul A.,Emsley, Jonas,Fischer, Peter M.,Chan, Weng C.
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supporting information; experimental part
p. 2589 - 2591
(2011/04/21)
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- Enyne metathesis/Bronsted acid-promoted heterocyclization
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The "one-pot" synthesis of nitrogen heterocycles and an oxygen heterocycle by enyne metathesis and in situ cyclization is reported
- Kalbarczyk, Kyle P.,Diver, Steven T.
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supporting information; experimental part
p. 2193 - 2196
(2009/08/07)
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