Pergamon Temhedmn: As~mmrm~. Vol. 8. No. Il. pp. 290~2912. 1997 0 1997 Published by Ekevier Science Ltd. All rights merved. Rimed in Great Brimin PII: !so!e74166@7)0032&5 0957-4166/97 $17.00 + 0.00 Acyclic C-nucleosides: synthesis of chiral l,l-diheteroaryl-alditols and X-ray crystal structure of 2,3,5-tri-O-benzyl-l,l-di-(2’~pyrryl)-l- deoxy-D-arabinitol Mat-a Comia* ,a * Silvia Capacchi,b Monica Del PO etto,a 4 Giorgio Pelosi b and Giovanna Gasparri Fava* a Dipartimento di Chimica Organica e lndustriale dell’Universit& Universita di Parma, Viale delle Scienze, I-43100 Parma, Italy b Dipartimento di Chimica Generale ed Inorganica, Chimica Analitica, Chimica Fisica e Centro di Studio per la Strutturistica Diffrattometrica del CNR, Universita di Parma, Viale delle Scienze, I-43100 Parma, Italy Abstract: Tetra-0-acetyl-D-ribose, penta-0-acetyl-D-glucose, 2,3;5,6-di-O- isopropylidene-D-mannofuranose, 2,3.5-tri-0-benzyl-D-arabinofuranose and 2,3,5,6-tetra- 0-benzyl-D-glucose react with pyrrole and indole, in presence of Lewis acids, to afford C-glycosylpyrroles and indoles in position 2 and 3 respectively (acyclic C-nucleosides, l-7). The crystal structure of 4 was determined by X-ray crystallography. 0 1997 Published by Else.vier Science Ltd It is known that a large number of drugs used in the treatment of neoplastic diseases and viral infections are nucleoside analogues,’ therefore in this field the search for new or improved drugs (safer and stronger) is a stimulating purpose. Moreover the synthesis of modified nucleosides has received great attention from the discovery of the potent antiviral activity of Acyclovir and overall AZT2 in particular many efforts are directed to C-nucleoside synthesis.’ Our previous work in the C-glycosides and C-nucleosides area has been characterized by a simple synthetic method, consisting of a direct, Lewis acid promoted arylation and hetero-arylation of glycosidic protected compounds.4 Thus, all these findings taken together prompted us to prepare and characterise, in the present paper, a series of acyclic C-nucleoside analogues, as 1,1 -dipyrrylalditols l-4 and 1,l -diindolylalditols 5-7, for testing and structure-activity studies. From our previous work, it emerged that when protected sugars were allowed to react with 1:4 or 15 molar ratio of phenols or pyrroles, in dichloromethane, the metallic promoter played a fundamental role in the reaction pathway to perform a selective reaction, and its choice strictly depended on the substrate, the sugar nature and the protecting group. In this paper we have analysed a number of Lewis acids, (including blends), and protected sugars to obtain a series of dinuclear (dipyrrolic and diindolic) alditols. First, we studied the direct synthesis of the new acetyl-protected C-glyco-dipyrrolic compounds (1 and 2, 15% and 20% yields, Figure l), starting from two sugars protected at the anomeric carbon C-l, as tetra-O-acetyl-D-ribose and penta- CJ-acetyl-D-glucose, with pyrrolylmagnesiumbromide (5: 1 molar ratio) in CHzC12 under ultrasonic irradiation for 30 minutes. The reactions also produced alditolic intermediates (not isolated), but using a 1: 1 blend between pyrrolylmagnesiumbromide and SnC14 the yields were enhanced to 35% and 40% respectively for compounds 1 and 2. The compounds 3 and 4 (Figure 1) were respectively synthesised from 2,3;5.6-di-O-isopropylidene- D-mannofuranose and from 2,3,5-tri-0-benzyl-D-arabinofuranose with pyrrolylmagnesiumbromide in toluene at 80°C for 12 h. Using only MgBr+, at 8O”C, instead of SnC4, as the metallic promoter, the synthesis of compounds 3 and 4, proceeded very cleanly under the same reaction conditions.’ In the * Corresponding author. Email: marac@vaimo.cce.unipr.it and chimic8@ipnmiv.cce.unipr.it 2905