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One-pot efficient synthesis of N(α)-urethane-protected β- and γ-amino acids.

Cal M, Jaremko M, Jaremko Ł, Stefanowicz P - Amino Acids (2012)

Bottom Line: 1-[(4-Methylphenyl)oxy]pyrrolidine-2,5-dione and 1-[(4-methylphenyl)oxy]piperidine-2,6-dione react in a Lossen-type reaction with primary alcohols in the presence of triethylamine to furnish corresponding N(α)-urethane-protected β-alanine and γ-aminopropionic acid (GABA), respectively, with excellent yields and purities, in an essentially "one-pot" procedure.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Chemistry, University of Wrocław, ul. F. Joliot-Curie 14, Wroclaw, Poland.

ABSTRACT
1-[(4-Methylphenyl)oxy]pyrrolidine-2,5-dione and 1-[(4-methylphenyl)oxy]piperidine-2,6-dione react in a Lossen-type reaction with primary alcohols in the presence of triethylamine to furnish corresponding N(α)-urethane-protected β-alanine and γ-aminopropionic acid (GABA), respectively, with excellent yields and purities, in an essentially "one-pot" procedure.

Show MeSH
A proposed reaction mechanism between the sulfonic esters of N-hydroxyimides and nucleophile (:NuH, e.g. alcohols, amines) (Groutas et al. 1986)
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Fig1: A proposed reaction mechanism between the sulfonic esters of N-hydroxyimides and nucleophile (:NuH, e.g. alcohols, amines) (Groutas et al. 1986)

Mentions: Sulfonic esters of N-hydroxyimides are well known for their inhibitory properties against serine proteases, mainly human leukocyte elastase (HLE) (Abell and Oldham 1999; Groutas et al. 1986, 1992, 1993, 1994; Neumann and Guetschow 1994; Tirouvanziam 2006). It has been elucidated that the mechanism of the proteases inhibition is based on the Lossen-like rearrangement (Groutas et al. 1986), which is induced by the nucleophilic amino acid residues present in the enzyme’s active center, like the hydroxyl side group of serine. Moreover, many investigations have shown that sulfonic esters of N-hydroxyimides are characterized also by the specific chemical reactivity toward nucleophilic compounds, like amines (Bauer and Exner 1974; Youssef and Abbady 1997; Abbady et al. 2000), hydrazine (Youssef and Abbady 1997; Abbady et al. 2000) and alcohols (Youssef and Abbady 1997; Chandrasekhar and Sridhar 2000; Sheikh et al. 2010). These properties may be at least partially explained as a result of flattened pyramidal geometry of the succinic ring’s nitrogen atom (Stefanowicz et al. 2006). This structural feature is common for every described sulfonic ester of N-hydroxyimide (Stefanowicz et al. 2005, 2006, 2007). The Lossen-like reaction between the nucleophiles and sulfonic esters of N-hydroxyimides (Fig. 1) opens a new route for the efficient one-pot synthesis of Nα-urethane-protected compounds. Since the urethane groups are often used as protective groups, the rearrangement products may be applied as building blocks in the synthesis of peptidomimetics.Fig. 1


One-pot efficient synthesis of N(α)-urethane-protected β- and γ-amino acids.

Cal M, Jaremko M, Jaremko Ł, Stefanowicz P - Amino Acids (2012)

A proposed reaction mechanism between the sulfonic esters of N-hydroxyimides and nucleophile (:NuH, e.g. alcohols, amines) (Groutas et al. 1986)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569585&req=5

Fig1: A proposed reaction mechanism between the sulfonic esters of N-hydroxyimides and nucleophile (:NuH, e.g. alcohols, amines) (Groutas et al. 1986)
Mentions: Sulfonic esters of N-hydroxyimides are well known for their inhibitory properties against serine proteases, mainly human leukocyte elastase (HLE) (Abell and Oldham 1999; Groutas et al. 1986, 1992, 1993, 1994; Neumann and Guetschow 1994; Tirouvanziam 2006). It has been elucidated that the mechanism of the proteases inhibition is based on the Lossen-like rearrangement (Groutas et al. 1986), which is induced by the nucleophilic amino acid residues present in the enzyme’s active center, like the hydroxyl side group of serine. Moreover, many investigations have shown that sulfonic esters of N-hydroxyimides are characterized also by the specific chemical reactivity toward nucleophilic compounds, like amines (Bauer and Exner 1974; Youssef and Abbady 1997; Abbady et al. 2000), hydrazine (Youssef and Abbady 1997; Abbady et al. 2000) and alcohols (Youssef and Abbady 1997; Chandrasekhar and Sridhar 2000; Sheikh et al. 2010). These properties may be at least partially explained as a result of flattened pyramidal geometry of the succinic ring’s nitrogen atom (Stefanowicz et al. 2006). This structural feature is common for every described sulfonic ester of N-hydroxyimide (Stefanowicz et al. 2005, 2006, 2007). The Lossen-like reaction between the nucleophiles and sulfonic esters of N-hydroxyimides (Fig. 1) opens a new route for the efficient one-pot synthesis of Nα-urethane-protected compounds. Since the urethane groups are often used as protective groups, the rearrangement products may be applied as building blocks in the synthesis of peptidomimetics.Fig. 1

Bottom Line: 1-[(4-Methylphenyl)oxy]pyrrolidine-2,5-dione and 1-[(4-methylphenyl)oxy]piperidine-2,6-dione react in a Lossen-type reaction with primary alcohols in the presence of triethylamine to furnish corresponding N(α)-urethane-protected β-alanine and γ-aminopropionic acid (GABA), respectively, with excellent yields and purities, in an essentially "one-pot" procedure.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Chemistry, University of Wrocław, ul. F. Joliot-Curie 14, Wroclaw, Poland.

ABSTRACT
1-[(4-Methylphenyl)oxy]pyrrolidine-2,5-dione and 1-[(4-methylphenyl)oxy]piperidine-2,6-dione react in a Lossen-type reaction with primary alcohols in the presence of triethylamine to furnish corresponding N(α)-urethane-protected β-alanine and γ-aminopropionic acid (GABA), respectively, with excellent yields and purities, in an essentially "one-pot" procedure.

Show MeSH