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Synlett 2009(8): 1227-1232  
DOI: 10.1055/s-0028-1088133
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Facile Synthesis of β-Amino Disulfides, Cystines, and Their Direct Incorporation into Peptides

Nasir Baig R. B.a, Catherine K. Kanimozhia, V. Sai Sudhira, Srinivasan Chandrasekaran*b
a Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India
b Honorary Professor, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India
Fax: +91(80)23602423; e-Mail: scn@orgchem.iisc.ernet.in;
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Publication History

Received 26 January 2009
Publication Date:
08 April 2009 (online)

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Abstract

Herein, we report a simple and efficient methodology for the synthesis of β-amino disulfides by regioselective ring opening of sulfamidates with benzyltriethylammonium tetrathiomolybdate [BnNEt3]2MoS4. Stability and reactivity of different protecting groups under the reaction conditions have been discussed. This methodology has also been extended to serine and threonine derived sulfamidates to furnish cystine and 3,3′-dimethyl cystine derivatives.

Key words

benzyltriethylammonium tetrathiomolybdate - β-amino disulfides - sulfamidates - cystine - peptides

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The nucleophilic ring opening of cyclic sulfamidates occur exclusively by SN2 substitution resulting in inversion of configuration as demonstrated by other groups.¹-³

16

In order to rule out the intervention of an elimination-addition mechanism in the formation of 15a,b and 20, the dehydro amino acid [Boc-ΔAbu-OMe] derived from Boc-Threo-OMe was treated with tetrathiomolybdate 1 and there was no reaction. This rules out the intermediacy of a dehydro amino acid in the formation of the product.