Design, iterative synthesis and structure of novel optically active trispiro-dendritic melamines incorporating ‘open-chain’ versus ‘closed-chain’ serinolic peripheral units Oana Moldovan a , Iulia Nagy a , Pedro Lameiras b , Cyril Antheaume c , Carmen Sacalis a , Mircea Darabantu a,⇑ a Babes-Bolyai University, Department of Chemistry, 11 Arany János St., 400028 Cluj-Napoca, Romania b University of Reims Champagne-Ardenne, ICMR, UMR 7312, BP 1039, 51687 Reims, France c University of Strasbourg, Faculty of Pharmacy, 74 Rhin St., BP 60024, 67401 Illkirch Cedex, France article info Article history: Received 2 March 2015 Accepted 1 May 2015 Available online 9 June 2015 Dedicated to Dr. Emil POP abstract Starting from commercial C-2-substituted 2-aminopropane-1,3-diols (serinols,‘open-chain’ peripheral units) and optically active amino-1,3-dioxanes (‘closed-chain’ peripheral units) as cycloacetals of (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol (p-nitrophenylserinol) or its 2-dimethylamino ana- logue, we herein report a new series of di- and trimeric G-1 trispiro-dendritic melamines, they were synthesised convergently by iterative chemoselective amination of cyanuric chloride. Depending on the number of hydroxymethyl groups in the ‘open-chain’ peripheral unit and the type of the rigid amino-anchorage (axial or equatorial) of the ‘closed-chain’ counterpart, the classic restricted rotation about the C(s-triazine)–N(exocyclic) partial double bonds induced, progressively, specific spatial arrange- ments in angularly connected G-0 and G-1 dendrons, including axial chirality in G-1 dimeric or G-1 trimeric melamines. Ó 2015 Elsevier Ltd. All rights reserved. 1. Introduction Serinol is the trivial nomenclature for 2-aminopropane-1,3-diol, seen as the reduced form of serine, and the parent term of a series comprising its C-substituted commercial analogues (Scheme 1). 1 The resourceful reactivity of C-2-substituted serinols A–C with electrophiles has been a challenging task in organic synthesis since the 1940-s. 2 Optically active C-1-substituted (1R,2R)-(p- nitro)phenylserinols are well-known key intermediates in the manu- facturing of the classical antibiotic Chloromycetin (Chloramphenicol) as early as 1947. 3,4 In a ‘dendritic context’, it was in 1985, when Newkome et al. 5 used TRIS C (Scheme 1) in the preparation of the first so-called ‘ar- borol’, that the chemistry of dendrimers was born. Later develop- ments of these ‘cascade syntheses’ 6 recommended TRIS as a very practical building-block for such polymeric architectures, because it could play almost all crucial roles within these innovative struc- tures: a peripheral unit, a tetravalent branch-cell and a core. 5b Serinol itself, as well as its 5-amino-1,3-dioxane derivatives, are of interest for iterative construction of macromolecules in biomedicine 7a–e and nanomaterials. 7f,g Except for our previously reported results, 8 no attention, however, has been paid to methylserinol A and ethylserinol B. Arising from the pioneering achievements of Simanek et al. in 2000, 9 there has been increasing interest in melamine-based den- drimers. Many approaches to this new class of macromolecules have been reported first, in the domain of iterative convergent 9,10 versus divergent syntheses 9,10a,11 by exploiting the ‘classic’ (but still versatile) chemoselective amination of cyanuric chloride. http://dx.doi.org/10.1016/j.tetasy.2015.05.003 0957-4166/Ó 2015 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Tel.: +40 264 59 38 33; fax: +40 264 59 08 18. E-mail addresses: darab@chem.ubbcluj.ro, m.darabantu@upcmail.ro (M. Darabantu). OH OH R 2 NH 2 R 1 1 2 R 1 H C-2-substituted serinols H H H C-1-substituted Serinols Ph p-NPh (p-O2N-C6H4) R 2 H Me Et CH 2 OH H H Trivial nomenclature Serinol Methylserinol (A) Ethylserinol (B) TRIS, THAM (C) (1R,2R) or (1S,2S) "Threo "-phenylserinol (1R,2R) or (1S,2S) "Threo "-p-nitrophenylserinol Scheme 1. Tetrahedron: Asymmetry 26 (2015) 683–701 Contents lists available at ScienceDirect Tetrahedron: Asymmetry journal homepage: www.elsevier.com/locate/tetasy