Cyclization of several linear penta‐ and heptapeptides with different metal ions studied by CD spectroscopy<sup>*</sup>

Liu, M.; Youqi, Tang; Fan, Keqiang; Jiang, Xiaohui; Lai, Luhua; Ye, Y.‐H

doi:10.1111/j.1399-3011.2004.00199.x

Cited by 26 publications

(21 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although this route constituted a synthesis of verticilide in six steps with 8% overall yield, an improved yield of verticilide by MCO was sought based on the hypothesis that the growing oligomers might bind to salt additives (16,17,(36)(37)(38)(39)(40)(41), which in turn, might lead to depsipeptide-salt complexes with a conformationally enhanced rate of macrocyclization relative to chain elongation. Known applications of this phenomenon to depsipeptide macrocycle synthesis are macrolactamization (38,39) reactions, which are conducted in a polar solvent that can readily solubilize the salt additive.…”

Section: Significancementioning

confidence: 99%

“…Known applications of this phenomenon to depsipeptide macrocycle synthesis are macrolactamization (38,39) reactions, which are conducted in a polar solvent that can readily solubilize the salt additive. However, the use of polar solvents and salt additives is contraindicated in a Mitsunobu reaction because of their ability to disrupt the reactive ion pairs (42)(43)(44), potentially slowing or stopping the coupling reaction entirely.…”

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control

Batiste

Johnston

2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Macrocyclic small molecules are attractive tools in the development of sensors, new materials, and therapeutics. Within early-stage drug discovery, they are increasingly sought for their potential to interact with broad surfaces of peptidic receptors rather than within their narrow folds and pockets. Cyclization of linear small molecule precursors is a straightforward strategy to constrain conformationally mobile motifs, but forging a macrocycle bond typically becomes more difficult at larger ring sizes. We report the development of a general approach to discrete collections of oligomeric macrocyclic depsipeptides using an oligomerization/macrocyclization process governed by a series of Mitsunobu reactions of hydroxy acid monomers. Ring sizes of 18, 24, 30, and 36 are formed in a single reaction from a didepsipeptide, whereas sizes of 24, 36, and 60 result from a tetradepsipeptide. The ring-size selectivity inherent to the approach can be modulated by salt additives that enhance the formation of specific ring sizes. Use of chemical synthesis to prepare the monomers suggests broad access to functionally and stereochemically diverse collections of natural product-like oligodepsipeptide macrocycles. Two cyclodepsipeptide natural products were prepared along with numerous unnatural oligomeric congeners to provide rapid access to discrete collections of complex macrocyclic small molecules from medium (18) to large (60) ring sizes.Mitsunobu | total synthesis | collective | macrocycle | oligomerization I nterest in the preparation and use of small molecules exhibiting macrocyclic rings is growing at a tremendous pace, driving the development of new approaches, new chemical reactions, and the underlying chemistry and tools (catalysts) to support them. Historically, studies of macrocyclization reactions have been guided by natural products bearing unusually large carbocycles or mediumand large-ring lactones, amides, and ethers. Fragmentation reactions of polycyclic molecules have long played a role in access to medium-sized macrocycles, whereas macrocyclizations to lactones and amides are often accomplished from linear precursors at high dilution. Insofar as these efforts were typically driven by the goal to prepare a specific macrocycle, often in the form relevant to a natural product synthesis or an engineered constraint to a peptide, absent from the field is an approach that provides rapid access to collections (1) of natural product-like macrocycles, particularly from stereochemically complex, functionally rich, linear precursors (2-6).Pioneers in this area have recorded some success (Fig. 1). Esterification reactions of activated hydroxy acids have led predominantly to diolides, (7-10) and in a single case, oligolides (11). Amidation reactions of activated polypeptides were central to the preparations of macrocyclic peptides by Rothe and Kreiss (12,13) and Wipf and coworkers (14, 15), but they were low yielding and size nonselective. Burke and coworkers (16,17) have shown that the efficiency of an 18-membered oligol...

show abstract

Section: Significancementioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control

Batiste

Johnston

2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The formulas of eight cyclic pentapeptides7, 8 are shown in Scheme . Boc: tert ‐butyloxylcarbonyl; Aph: β‐(aminophenyl)‐alanine; Nal: β‐naphthyl‐alanine; Pal: β‐(3‐pyridyl)‐alanine; Phg: phenylglycine.…”

Section: Methodsmentioning

confidence: 99%

Discrimination of cyclic peptide diastereomers by electrospray ionization tandem mass spectrometry

Zheng

Liu

et al. 2009

J. Mass Spectrom.

View full text Add to dashboard Cite

In this research, the characteristic ions' abundance ratio between two isomers A and B in MS/MS mass spectra was defined as a parameter for discriminating diastereomers. Through this ratio, the discrimination of four pairs of cyclic peptide (CP) diastereomers was successfully achieved. Furthermore, in the analysis of diastereomers' mixtures, both calibration curve and calculational methods were substantiated to have high precision and accuracy. The average absolute errors of the two methods were 2.0 and 2.5% in the 48 measurements of 16 samples, respectively. This research provided a promising approach for the analysis of the CP diastereomers in the fields of asymmetrical synthesis, chiral natural products and structural biology by ESI-MS/MS.

show abstract

“…However in a LiCl/dimethyl formamide solvent mixture, exclusive monomeric cyclization was observed through a nucleophilic displacement of the N-terminal chloroacetyl moiety by the C-terminal cysteine thiol. Ye and co-workers have shown that sodium ions are suitable for promoting the cyclization of linear pentapeptides, whereas larger caesium ions can effectively promote the cyclization of heptapeptides 54,55 . Supported by molecular mechanics calculations, Ye and co-authors propose that these alkali metal ions promote peptide macrocyclization by initially binding the carbonyl and amide groups at the C-terminus of a peptide.…”

Section: Metal-ion-assisted Cyclizationsmentioning

confidence: 98%

Contemporary strategies for peptide macrocyclization

2011

View full text Add to dashboard Cite

Peptide macrocycles have found applications that range from drug discovery to nanomaterials. These ring-shaped molecules have shown remarkable capacity for functional fine-tuning. Such capacity is enabled by the possibility of adjusting the peptide conformation using the techniques of chemical synthesis. Cyclic peptides have been difficult, and often impossible, to prepare using traditional synthetic methods. For macrocyclization to occur, the activated peptide must adopt an entropically disfavoured pre-cyclization conformation before forming the desired product. Here, we review recent solutions to some of the major challenges in this important area of contemporary synthesis.

show abstract

Cyclization of several linear penta‐ and heptapeptides with different metal ions studied by CD spectroscopy^*

Cited by 26 publications

References 26 publications

Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control

Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control

Discrimination of cyclic peptide diastereomers by electrospray ionization tandem mass spectrometry

Contemporary strategies for peptide macrocyclization

Contact Info

Product

Resources

About

Cyclization of several linear penta‐ and heptapeptides with different metal ions studied by CD spectroscopy*

Cited by 26 publications

References 26 publications

Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control

Rapid synthesis of cyclic oligomeric depsipeptides with positional, stereochemical, and macrocycle size distribution control

Discrimination of cyclic peptide diastereomers by electrospray ionization tandem mass spectrometry

Contemporary strategies for peptide macrocyclization

Contact Info

Product

Resources

About

Cyclization of several linear penta‐ and heptapeptides with different metal ions studied by CD spectroscopy^*