Now showing 1 - 8 of 8
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An in vitro-in vivo sequential cascade for the synthesis of iminosugars from aldoses

2021-06-15, Kuska, Justyna, Taday, Freya, Yeow, Kathryn, Ryan, James, O'Reilly, Elaine

Here, we report a chemoenzymatic approach for the preparation of a small panel of biologically important iminosugars from readily available aldoses. Our approach involves an in vitro transaminase-mediated amination of aldoses in combination with an in vivo selective oxidation of the chemically protected transaminase products, using Gluconobacter oxydans DSM 2003 whole cells. Chemically catalysed deprotection and reduction steps afford a selection of valuable iminocyclitols.

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Combining bio- and organocatalysis for the synthesis of piperidine alkaloids

2022-02-07, Taday, Freya, Cairns, Ryan, O'Connell, Adam, O'Reilly, Elaine

There is continued interest in developing cascade processes for the synthesis of key chiral building blocks and bioactive natural products (or analogues). Here, we report a hybrid bio-organocatalytic cascade for the synthesis of a small panel of 2-substituted piperidines, relying on a transaminase to generate a key reactive intermediate for the complexity building Mannich reaction.

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Preparation of iminosugars from aminopolyols via selective oxidation using galactose oxidase

2022-11-07, Yeow, Kathryn, Haarr, Marianne B., Muldoon, Jimmy, O'Reilly, Elaine

Minimally protected aminopolyols are novel substrates for the galactose oxidase variant F2. Site-selective oxidation proceeds at the terminal primary alcohol, followed by spontaneous cyclisation to afford stable hemiaminal/hemiacetal anomers of the piperidine and azepane scaffolds, with isolated yields of up to 94%. Simultaneous deprotection and reduction occured readily to afford valuable and biologically relevant iminosugars.

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One-step diketopiperazine synthesis using phase transfer catalysis

2009-04-15, O'Reilly, Elaine, Lestini, Elena, Balducci, Daniele, Paradisi, Francesca

A simple and efficient one-step procedure is described for the synthesis of a number of symmetrical 1,4-disubstituted piperazine-2,5-diones under phase transfer conditions. The reactions are carried out at room temperature, starting from a suitable N-chloroacetamide in the presence of an aqueous solution of sodium hydroxide. Piperazine-2,5-diones were obtained with excellent selectivity in yields of up to 90%.

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Transaminase-Mediated Amine Borrowing via Shuttle Biocatalysis

2022-01-14, Taday, Freya, Ryan, James, O’Sullivan, Rachel, O'Reilly, Elaine

Shuttle catalysis has emerged as a useful methodology for the reversible transfer of small functional groups, such as CO and HCN, and goes far beyond transfer hydrogenation chemistry. While a biocatalytic hydrogen-borrowing methodology is well established, the biocatalytic borrowing of alternative functional groups has not yet been realized. Herein, we present a new concept of amine borrowing via biocatalytic shuttle catalysis, which has no counterpart in chemo-shuttle catalysis and allows efficient intermolecular amine shuttling to generate reactive intermediates in situ. By coupling this dynamic exchange with an irreversible downstream step to displace the reaction equilibrium in the forward direction, high conversion to target products can be achieved. We showcase the potential of this amine-borrowing methodology using a biocatalytic equivalent of both the Knorr-pyrrole synthesis and Pictet–Spengler reaction.

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A stereoselective synthesis of α-deuterium labelled (S)-α-amino acids

2010, O'Reilly, Elaine, Balducci, Daniele, Paradisi, Francesca

An atom-efficient and stereoselective synthesis has been developed for the preparation of a-2H-labelled(S)-a-amino acids, starting from a novel chiral diketopiperazine scaffold. Efficient mono-alkylation of the chiral template afforded the (S)-substituted adducts with the nature of the electrophile significantly effecting the stereochemical outcome. Subsequent alkylation was totally selective producing the 1,4-cis adduct as the sole diastereoisomer. The deprotection was carried out using cerium ammonium nitrate followed by acid hydrolysis affording the enantipure a-amino acids.

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From amines to diketopiperazines: a one-pot approach

2010-03-31, O'Reilly, Elaine, Pes, Lara, Paradisi, Francesca

An efficient one-pot synthesis is described for the preparation of 1,4-disubstituted piperazine-2,5-diones starting from a suitable amine and chloroacetyl chloride in the presence of an aqueous base. The resulting chloroacetamide is cyclised in situ by employing the phase-transfer (PT) catalyst, benzyltriethylammonium chloride (TEBA). The products are isolated in excellent yields of up to 90%.

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Synthesis of a conformationally constrained delta-amino acid building block

2013-02, O'Reilly, Elaine, Pes, Lara, Ortin, Yannick, Müller-Bunz, Helge, Paradisi, Francesca

Conformationally restricted amino acids are important components in peptidomimetics and drug design. Herein, we describe the synthesis of a novel, non-proteinogenic constrained delta amino acid containing a cyclobutane ring, cis-3(aminomethyl)cyclobutane carboxylic acid (ACCA). The synthesis of the target amino acid was achieved in seven steps, with the key reaction being a base induced intramolecular nucleophilic substitution. A small library of dipeptides was prepared through the coupling of ACCA with proteinogenic amino acids.