An expedient conversion of α-amino acids into Weinreb amides using COMU® as a coupling agent

Tyrrell, Elizabeth; Brawn, Peter; Carew, Mark; Greenwood, Iain A.

doi:10.1016/j.tetlet.2010.10.169

Cited by 14 publications

(25 citation statements)

References 42 publications

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“…One of the most celebrated features of 4 is its high solubility not only in organic solvents commonly employed in peptide synthesis, but also in aqueous environments, facilitating removal of excess reagents employed during solution‐phase approaches 10,26. Given the relevance of this issue to the overall performance of the reagent, a direct comparison between OxymaPure ( 4 ) and K‐Oxyma ( 6 ) was conducted in a variety of solvents at different temperatures (Table 1).…”

Section: Resultsmentioning

confidence: 99%

K‐Oxyma: a Strong Acylation‐Promoting, 2‐CTC Resin‐Friendly Coupling Additive

et al. 2013

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Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond formation, in which the N‐hydroxylamine group is replaced by a potassium salt. The complete suppression of its acidity converts K‐Oxyma into the most suitable coupling choice when peptides are assembled on highly acid‐labile solid‐supports. The coupling efficiency and diminished prospects for epimerization are conserved relative to OxymaPure. In addition, K‐Oxyma displays excellent solubility in a variety of organic solvents and undergoes safer decomposition than classical 1‐hydroxybenzotriazole additives.

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Section: Resultsmentioning

confidence: 99%

K‐Oxyma: a Strong Acylation‐Promoting, 2‐CTC Resin‐Friendly Coupling Additive

et al. 2013

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“…of 2,4,6‐trimethylpyridine is employed . The outstanding ability of COMU ( 16 ) to reduce loss of configuration has been confirmed recently by other authors . The combination of COMU ( 16 ) and Oxyma ( 15 ) is an alternative to maintain acceptable epimerization levels, which can also be used to decrease the risk of guanidylation.…”

Section: Introductionmentioning

confidence: 89%

“…Only 4 years later, one of our groups reevaluated ethyl 2-cyano-2-(hydroxyimino)acetate (renamed as Oxyma 15, Figure 2), which had first been reported a few decades ago [10]. Although cyanooximes are well appreciated in organometallic chemistry, Oxyma (15) had not been used in peptide synthesis, beyond the related uronium salts HOTU (13) and TOTU (14) [3,8,10]. The recent exhaustive reconsideration of Oxyma as an additive to carbodiimides revealed an improved suppression of stereomutation and coupling yields than HOBt (1) and often comparable with HOAt (2).…”

Section: Comu As Efficient Coupling Reagentmentioning

confidence: 99%

“…The remarkable solubility properties of COMU in organic solvents used in peptide synthesis were confirmed by White and co‐workers, showing also a significant improvement over HDMC ( 12 ), due to the contribution of Oxyma ( 15 ) . Furthermore, solution‐phase acylations with COMU ( 16 ) are facilitated by the great water solubility of its by‐products, such as the corresponding urea, deriving in cleaner workup removal in contrast to benzotriazole‐based reagents . An additional distinctive feature of COMU ( 16 ) is that its coupling reactions can be monitored by a change of color of the solution, which depends on the base used, thus indicating the end point .…”

Section: Introductionmentioning

confidence: 99%

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COMU: scope and limitations of the latest innovation in peptide acyl transfer reagents

Subirós‐Funosas

Nieto-Rodriguez

Jensen

et al. 2013

Journal of Peptide Science

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The methodology for peptide bond formation is undergoing a continuous evolution where the main actors are being renewed. In recent years, coupling reagents based on the Oxyma scaffold, such as the uronium salt COMU, has been a groundbreaking contribution to the field. The advantages of COMU over classic benzotriazole-based reagents (HATU, HBTU, HCTU, TBTU) were proven in terms of solubility and coupling efficiency in bulky junctions in our groups and others. However, some aspects of the use of COMU need to be revised and improved, such as the stability of commercial samples in organic solvents, which hampers the compatibility with long synthesis in automated synthesizers. In this review, an overview of the main features and suggestions to improve the use of COMU are presented, along with a discussion on the best conditions for its use in microwave-assisted peptide robots.

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“…COMU has been employed as an excellent choice of coupling reagent in solution phase and solid phase peptide synthesis. Tyrrell et al (2011) synthesized Weinreb amides employing COMU as a coupling reagent. Zhang et al (2011) used the similar protocol for the synthesis of rubescesin S. Synthesis of O-acyl isodipeptides had been reported by our group using COMU (Samarasimhareddy et al 2012).…”

Section: Introductionmentioning

confidence: 99%