Synthesis of novel O-acylated-D-ribono-1,5-lactones and structural assignment supported by conventional NOESY-NMR and x-ray analysis

Abstract

Este trabalho apresenta um método simples para a caracterização estrutural de 3,4-O-benzilideno-D-ribono-1,5-lactonas e análogos, fundamentado em técnicas convencionais de RMN e experimentos de NOESY em solução. 2-O-Acil-3,4-O-benzilideno-D-ribono-1,5-lactonas foram preparadas em bons rendimentos a partir da acilação das lactonas de Zinner empregando cloretos de ácido sob condições básicas. A estrutura de 2-O-(4-nitrobenzoil)-3,4-O-benzilideno-D-ribono-1,5-lactona foi determinada por difração de raios-X e confirmou, de forma inequívoca, os dados espectroscópicos obtidos.A practical method for the structural assignment of 3,4-O-benzylidene-D-ribono-1,5-lactones and analogues using conventional NMR techniques and NOESY measurements in solution is described. 2-O-Acyl-3,4-O-benzylidene-D-ribono-1,5-lactones were prepared in good yields by acylation of Zinner's lactone with acyl chlorides under mildly basic conditions. Structural determination of 2-O-(4-nitrobenzoyl)-3,4-O-benzylidene-D-ribono-1,5-lactone was achieved by single crystal x-ray diffraction, which supports the results based on spectroscopic data. Keywords:O-acyl-D-ribono-1,5-lactones, D-ribono-1,4-lactones, structural elucidation, sugar lactones, acylation IntroductionSeveral carbohydrates are easily available from renewable resources 1,2 and constitute a major class of building blocks for the synthesis of natural products and biologically active compounds. [3][4][5][6][7] However, the synthesis of novel carbohydrate-based molecules and their unequivocal structural elucidation are usually difficult to accomplish by simple and predictable methods. [8][9][10] The chemical complexity of carbohydrate derivatives, due to subtle differences in reactivity of the various hydroxyl groups and the possible formation of species co-existing in equilibrium under different reaction conditions, may lead to unexpected processes ranging from rearrangements to functional group migrations. 11,12 In many cases, single crystal X-ray analysis is the only reliable method for correct structural and conformational assignments. 13,14 Aldonolactones 15 (modified sugars with the anomeric centre in its higher oxidation state) have been widely employed in synthesis as an alternative to simple carbohydrates. D-Ribono-1,4-lactone (D-ribono--lactone, 1) is one of the most useful chiral precursors from this class, [16][17][18][19] although the issues associated with product characterization due to unpredictable transformations are also present to a great extent. For instance, the product obtained from the reaction of D-ribono-1,4-lactone (1) with benzaldehyde in acidic medium, which was initially assigned as being 3,5-O-benzylidene-D-ribono-1,4-lactone (2), 20,21 had the correct structure unequivocally established as 3,4-O-benzylidene-D-ribono-1,5-lactone (3) by single crystal X-ray diffraction analysis of its O-acetyl derivative (Scheme 1). 22 A complex rearrangement involving acetal migration and ring expansion sequences has been proposed for this transformation. 10,14 Therefore, the sc...

S-Ribosylhomocysteine analogues modified at the ribosyl C-4 position

“…The structure of one such byproduct isolated from the reaction of 15c with Hcy was tentatively assigned as the 2,3- O -isopropylidene-4-C-octyl-D-ribono-1,5-lactone (see note under the experimental procedure for 17c ) based on the spectroscopic analysis ( 1 H & 13 C NMR and HRMS) and by comparison with the similar ribono-1,5-lactones. [41]…”