FULL PAPER Stereoselective Synthesis of ()-Deacetylanisomycin Pedro Merino,* [a] Santiago Franco, [a] Diego Lafuente, [a] Francisco Merchan, [a] Julia Revuelta, [a] and Tomas Tejero [a] Dedicated to Prof. E. Mele ´ndez on the occasion of his retirement Keywords: Nitrogen heterocycles / Nucleophilic addition / Nitrones / Hydroxylamines / Grignard reaction A stereoselective synthesis of (-)-deacetylanisomycin has been achieved from a nitrone derived from l-threose in 6 steps and 53.7% overall yield. The key step of the synthesis is the nucleophilic addition of a Grignard derivative with complete diastereofacial selectivity. Introduction Anisomycin (1) is a dihydroxylated pyrrolidine originally isolated from various species of Streptomyces . [1] Since its initial isolation 1 has aroused considerable interest due to its potent and specific antibiotic activity [2] against several microorganisms. It also inhibits the ribosomal peptide syn- thesis [3] and exhibits high antitumor activity. [4] In light of these diverse biological activities, it is not surprising that anisomycin has received considerable attention as a syn- thetic target, with no less than 20 total syntheses of the molecule having been reported to date. [5-8] These syntheses include preparation of (-)-deacetylanisomycin 2 since it is well documented that anisomycin 1 can be easily prepared from 2. [9] In light of the high interest in anisomycin and its deacetyl derivative 2, we undertook a study designed to provide a highly stereoselective synthesis of 2. Specifically, we envis- aged the use of a nucleophilic addition to an -threose-de- rived nitrone for the introduction of the (4-methoxyphe- nyl)methyl moiety. Nucleophilic additionto a cyclic nitrone [a] Laboratorio de Sintesis Asimetrica, Departamento de Quimica Organica, Facultad de Ciencias-ICMA, Universidad de Zaragoza, 50009 Zaragoza, Aragon, Spain Fax: (internat.) + 34-976/762075 E-mail: pmerino@posta.unizar.es Eur. J. Org. Chem. 2003, 2877-2881 DOI: 10.1002/ejoc.200300091  2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2877 ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) has previously been used for synthesizing 2 by Petrini et al. [10] However, the reaction showed poor selectivity (dr = 3:2). Results and Discussion Our synthesis starts with nitrone 4, which can be easily obtained from commercially available (-)-2,3-O-isopro- pylidene--threitol in three steps and in a 51.6% overall yield (Scheme 1). Nucleophilic additions to acyclic α-alkoxy nitrones have been used previously for highly stereoselective syntheses of a variety of nitrogen-containing compounds in our laboratory. [11] Scheme 1 Nitrone 4 was treated with p-methoxybenzylmagnesium chloride or bromide under several different reaction con- ditions and in the presence or absence of additives in order to achieve the best selectivity (Scheme 2, Table 1). The ab- sence of an additive, the use of THF as solvent, and ad- dition of excess p-methoxybenzylmagnesium chloride (3.0