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Synthesis of peptides and pyrazines from β-amino alcohols through extrusion of H2 catalyzed by ruthenium pincer complexes: ligand-controlled selectivity.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Gnanaprakasam, Boopathy Balaraman, Ekambaram Ben-David, Yehoshoa Milstein, David |
| Copyright Year | 2011 |
| Abstract | Peptides constitute one of the most important families of compounds in chemistry and biology. Short peptides have found intriguing biological and synthetic applications. For example, the conformational rigidity of cyclic peptides makes them attractive for drug discovery and biomedical research. Several cyclic peptides that show intriguing biological activity are found in nature. Cyclic peptides have been discovered that are novel antibiotics, enzyme inhibitors, and receptor antagonists. Among them are the smallest cyclopeptides, 2,5diketopiperazines derivatives, which are commonly found as natural products. These compounds exhibit high-affinity binding to a large variety of receptors and show a broad range of biological acitivities, including antimicrobial, antitumoral, antiviral, and neuroprotective effects. 2,5-diketopiperazine derivatives are synthesized in solution or on the solid phase from commercially available and appropriately protected chiral a-amino acids in processes that are usually not atom-economical and generate considerable amounts of waste. Large libraries of cyclic peptides are accessible through solid-phase split-and-pool synthesis, and various methods were developed for their syntheses. Very recently, the synthesis of diketopiperazines from amino acids under microwave irradiation was reported. Green, atom-economical methods for the generation of peptides are highly desirable. We have developed several reactions catalyzed by PNN and PNP Ru pincer complexes based on pyridine, bipyridine, 13] and acridine and have discovered a new mode of metal–ligand cooperation based on ligand aromatization–dearomatization. For example, the PNN Ru pincer complex 1 (Scheme 1) catalyzes the direct synthesis of amides from alcohols and amines with liberation of H2 [17] (Scheme 2, Eq. (1)). Several reports on amide formation by dehydrogenative coupling of amines with alcohols appeared later. Unlike complex 1, the analogous PNP complex 2 (or complex 3 in the presence of an equivalent of base) catalyzes the coupling of amines with alcohols to form imines rather than amides with liberation of H2 and H2O (Scheme 2, Eq. (2)). Herein we report a novel method for peptide synthesis, which involves dehydrogenative coupling of b-amino alcohols with extrusion of H2 catalyzed by complex 1. This environmentally benign and atom-economical reaction proceeds under neutral reaction conditions without the use of toxic reagents, activators, condensing agents, or other additives. With the analogous PNP complex 2, a strikingly different reaction takes place, which leads to pyrazines with extrusion of H2 and H2O. Initially, we were interested to see whether coupling of bamino alcohols with amines can be accomplished and whether racemization would be involved. Reaction of (S)-2-amino-3phenylpropan-1-ol (4), benzylamine, and 1 mol% of the catalyst 1 in toluene at reflux for six hours led to (S)-2-aminoN-benzyl-3-phenylpropanamide 5 in 58% yield after column chromatography (Scheme 3). The specific rotation of amide 5 obtained from the catalysis is essentially the same as reported (+ 16.08). The neutral reaction conditions likely help to prevent racemization. Scheme 1. PNNand PNP-type pincer ruthenium complexes. |
| File Format | PDF HTM / HTML |
| DOI | 10.1002/anie.201105876 |
| PubMed reference number | 22031234 |
| Journal | Medline |
| Volume Number | 50 |
| Issue Number | 51 |
| Alternate Webpage(s) | http://gnanaprakasamb.weebly.com/uploads/7/4/9/0/7490987/paper_16.pdf |
| Alternate Webpage(s) | https://doi.org/10.1002/anie.201105876 |
| Journal | Angewandte Chemie |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
