Readily available, low-cost 4R-hydroxy-l-proline (Hyp) is introduced as a “doubly
customizable” unit for the generation of libraries of structurally
diverse compounds. Hyp can be cleaved at two points, followed by the
introduction of new functionalities. In the first cycle, the removal
and replacement of the carboxylic group are carried out, followed
(second cycle) by the scission of the 4,5-position and manipulation
of the resulting chains. In this way, three new chains are generated
and can be transformed independently to afford a diversity of products
with tailored substituents, such as β-amino aldehydes, diamines,
β-amino acid derivatives, including N-alkylated ones, or modified
peptides. Many of these products are high-profit compounds but, in
spite of their commercial value, are still scarce. Moreover, the process
takes place with stereochemical control, and either pure R or S isomers can be obtained with small variations
of the synthetic route.
Domino or sequential processes initiated by cleavage of O radicals has led to the conversion of low‐cost, readily available substrates into high‐profit products. The optimization of these processes by using different activation sources (irradiation with visible light, microwaves, and conventional heating) is described herein, as well as their application to the conversion of carbohydrates, amino acids, peptides, and terpenes into valuable derivatives.
An efficient conversion
of hydroxyproline “customizable”
units into new amino acids with a variety of N-alkyl
substituents is described. The process is versatile and can afford
valuable N-methyl amino acids and N,O-acetals. In addition, it allows the introduction
of N-homoallylic substituents and N-chains with terminal
ester, ketone, or cyano groups. These chains could be used for peptide
extension or conjugation to other molecules (e.g., by olefin metathesis,
peptide ligation, etc.). The transformation is carried out in just
two (for R = CH2OAc) or three steps (scission of the pyrrolidine
ring, manipulation of the α-chain, and the N-substituent) under mild, metal-free conditions, affording products
with high optical purity.
Libraries of compounds containing unnatural amino acids or amino acid analogues were prepared from inexpensive substrates using sustainable processes [1][2][3]. The compounds were evaluated for antimicrobial activity against different pathogens.
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