Pergamon Tetrahedron: Asymmetry 9 (1998) 2137–2154 TETRAHEDRON: ASYMMETRY Spirodiketopiperazines of mannofuranose: carbopeptoid α-amino acid esters at the anomeric position of mannofuranose Juan C. Estevez, c Jonathan W. Burton, a Ramon J. Estevez, a,c Helen Ardron, a Mark R. Wormald, b Raymond A. Dwek, b David Brown d and George W. J. Fleet a,∗ a Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford OX1 3QY, UK b Glycobiology Institute, Biochemistry Department, Oxford University, South Parks Road, Oxford OX1 3QU, UK c Departamento de Química Orgánica, Universidade de Santiago de Compostela, e Sección de Alcaloides do C.S.I.C., 15706 Santiago de Compostela, Spain d GlaxoWellcome Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK Received 25 April 1998; accepted 15 May 1998 Abstract Epimeric mannofuranose anomeric aminoesters are prepared from readily available azidolactones and can act as building blocks for the incorporation of mannofuranose units into peptide chains [carbopeptoids]; alternative acylating conditions allow either rapid acylation of the more stable but kinetically hindered amine or reaction with the less hindered but less stable amine to allow control of the anomeric configuration of the products. This is exemplified by coupling of the aminoesters with glycine derivatives to give dipeptide equivalents, and subsequent cyclization to spiro diketopiperazines. Anomers with the nitrogen function cis to the 2,3-diol are more stable than those with nitrogen trans; mannofuranose derivatives are more stable than the mannopyranose isomers. © 1998 Published by Elsevier Science Ltd. All rights reserved. 1. Introduction It has been suggested that pyranose amino acid fragments exemplified by 1 can be used as peptide-bond linked carbohydrates (carbopeptoids) to provide extra diversity and carbohydrate structure in the search for ligand lead and drug discovery. 1 The same pyranose amino acid moiety 1 has been used as a flexible β-turn mimic and other aminopyranose carboxylates may be able to act as dipeptide isosteres, perhaps inducing β- and γ-turns. 2 Pyranose amino acid fragments such as 2 have also been used in the synthesis of peptide sugar hybrids. 3 Other pyranose derivatives have been studied as novel oligonucleotide backbone analogues, 4 building blocks for combinatorial synthesis, 5 and other peptide–carbohydrate hybrids. 6 Some ∗ Corresponding author. E-mail: george.fleet@chem.ox.ac.uk 0957-4166/98/$19.00 © 1998 Published by Elsevier Science Ltd. All rights reserved. PII: S0957-4166(98)00206-7