Pergamon Tetrahedron Letters 41 (2000) 2907–2910 TETRAHEDRON LETTERS Symmetrically-substituted decalin-based scaffolds Zoi F. Plyta, a Eberhard Heller, a Françoise Dumas, a,* Christine Miet, a Jacqueline Mahuteau, a Jean d’Angelo, a,* Juan Caturla b and Marie-Elise Tran Huu Dau c a Centre d’Etudes Pharmaceutiques, Université de Paris Sud, Laboratoire de Synthèse Organique, BIOCIS, Unité associée au CNRS 5, rue J.-B. Clément, 92296 Châtenay-Malabry, France b Philipps-Universität Marburg, Fachbereich Chemie, 35032, Marburg, Germany c Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif sur Yvette, France Received 31 January 2000; accepted 18 February 2000 Abstract The synthesis of a chiral scaffold was achieved by coupling a decalintriol platform with a NH-Boc protected α-ethylenic γ-amino acid. The two side chains of this molecule strongly self-associate through intramolecular hydrogen bonding involving the NH-Boc residues. © 2000 Published by Elsevier Science Ltd. All rights reserved. Keywords: conformation; hydrogen bonding; molecular modeling; molecular recognition; NMR. Important progress has been made in synthesizing catalytic systems for asymmetric recognition. 1–3 As learned from the chemistry of enzymes, selective catalysis may be achieved through the cooperative action of functional groups which converge on a substrate positioned centrally in an ‘active site’. The catalytic/binding units can be located separately on a rigid platform, such that they can surround a substrate molecule with an array of convergent functionality. Furthermore, since it is desirable to design molecular catalysts as heterogeneous systems viable through many cycles of reuse, the scaffold should require a further anchor point through which it can be connected to a polymer support. The aim of this paper was to elaborate new scaffolds in which two identical chiral chains, at a separation distance of approximately 5 Å, protrude orthogonally to the same face of a rigid framework. It was our hope that such a topology forces the two chains to converge and to act as a part of an ‘active site’, featuring an asymmetric microenvironment. An advantage offered by the presence of two identical side chains is that, provided they satisfy definite structural requirements (vide infra the criteria of selection of 6), they would cooperate within this ‘active site’ as chiral ligands of virtual C 2 -symmetry. We reasoned that trans-fused decalintriol 4 may constitute an attractive, simple meso tripodal platform, so that the introduction of two identical chiral legs through esterification of the axial secondary alcohol groups at C-2 and C-7 could afford the desired chiral scaffold, the angular hydroxymethyl group at C-4a ensuring a site of attachment to the polymer matrix. We report here such a structure (7). As evidenced by * Corresponding authors. E-mail: jean.dangelo@cep.u-psud.fr (J. d’Angelo) 0040-4039/00/$ - see front matter © 2000 Published by Elsevier Science Ltd. All rights reserved. PII: S0040-4039(00)00311-7 tetl 16591