A Convenient Approach to the Synthesis of ω-Heterocyclic Amino Acids from Carboxy Lactams through Ring-Chain Transformation; Part 1: Synthesis of (2S)-/(2R)-2-Amino-4-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)butyric Acid

Rakesh K. Singh; Neelima Sinha; Sanjay Jain; Mohammad Salman; Fehmida Naqvi; Nitya Anand

doi:10.1055/s-2005-872166

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A Convenient Approach to the Synthesis of ω-Heterocyclic Amino Acids from Carboxy Lactams through Ring-Chain Transformation; Part 1: Synthesis of (2S)-/(2R)-2-Amino-4-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)butyric Acid

Rakesh K. Singh^a, Neelima Sinha^a, Sanjay Jain*^a, Mohammad Salman^a, Fehmida Naqvi^b, Nitya Anand*^a
^a Medicinal Chemistry Division, New Drug Discovery Research, Ranbaxy Laboratories Limited, R&D II, Plot # 20, Sector 18, Udyog Vihar Industrial Area, Gurgaon 122001, India
Fax: +91(20)25171329; e-Mail: sanjayjain@lupinpharma.com; e-Mail: nityaanand@satyam.net.in;
^b Department of Chemistry, Jamia Millia Islamia, New Delhi 110015, India

Abstract

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Abstract

A general method is reported for the synthesis of ω-heterocyclic α-amino acids, which involves preparation of enaminone intermediates from thiolactams, followed by reaction with dinucleophiles, resulting in a single-step condensation and ring-chain transformation to the desired ω-heterocyclic α-amino acids after deprotection of amine and carboxylic group. The reaction steps preserve the chirality of the parent-substituted lactam. The method is illustrated by the synthesis of (2S)- and (2R)-2-amino-4-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)butyric acids.

Key words

amino acids - ring opening - chirality - lactams - hydrogenations

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References

Current address: Medicinal Chemistry Division, New Chemical Entity Research, Lupin Research Park, 46/47A, Village Nande, Taluka Mulshi, Pune 411 042, India.

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