A Facile Synthesis of Saturated 2-Nitrosugar Derivatives Jose ´ M. Vega-Pe ´rez,* Jose ´ I. Candela, and Fernando Iglesias-Guerra Departamento de Quı ´mica Orga ´ nica y Farmace ´ utica, Facultad de Farmacia, Universidad de Sevilla, 41071 Sevilla, Spain Received April 21, 1997 X Saturated 2-nitrosugar derivatives (11-20 and 22) are easily synthesized by oxidation with m-CPBA of readily available corresponding 2-aminosugars (1-10 and 21), in excellent yield. Alkyl 4,6-O- benzylidene-2-deoxy-2-nitro-D-hexopyranosides suffer O-alkylation and O-acylation in the usual conditions. These 3-O-acetyl-2-nitrosugar derivatives gave the corresponding 2-nitroalkene derivative, which reacts in situ with nuclephiles in high stereoselectivity. Introduction We are interested in the synthesis of saturated 2-ni- trosugar derivatives as key intermediates to obtain D-glucosamine derivatives modified at positions 2 and/ or 3 of the sugar ring. Many sugars with a nitro group have been synthesized, and their versatility as synthetic intermediates is widely accepted. 1 Nevertheless, al- though there are many articles about 3-nitrosugar de- rivatives synthesis, the number of references on the synthesis of saturated 2-nitrosugar derivatives is sub- stantially more limited. Lemieux et al. 2,3 obtained alkyl 2-nitroglucopyranoside derivatives by treatment of glucal with N 2 O 4 and then glycosidation of 2-nitroglucal by alcohols. These compounds represent the first cyclic carbohydrate bearing a nitro group on carbon 2. 1d Various types of 2-nitrosugars were synthesized by oxidation of the corresponding oximes with trifluoroper- oxyacetic acid in which all hydroxyl groups were pro- tected by an ether or acetal function. 4-7 Another important synthetic route contains a long sequence of reactions with a 3-nitroalkene as intermedi- ate, which gives 2-nitroalkene by isomerization with sodium nitrite. 8-11 This key reaction gives low yields (15-45%). More recently, a different procedure for 2-nitroglycal synthesis from 2-deoxyglycal and NO 2 BF 4 has been proposed. 12 These 2-nitroglycals were transformed into saturated 2-nitrosugar derivatives by different methods. In summary, 2-nitroalkenes or 2-nitroglycals are the key intermediates for most saturated 2-nitrosugars syn- theses. In general, these routes mean many reaction steps, mixtures of compounds, and low yields. In this paper, we propose an alternative way to obtain alkyl (aryl) 2-deoxy-2-nitro-D-glucopyranosides from ap- propriately protected 2-aminoglycosides, by oxidation of the amino group. Although the oxidation of an amino compound to nitro compound is known, 13,14 this procedure has not been used previously in the case of 2-aminosug- ars. We have used some of these 2-aminoglucosides as starting products in other, previous aspects of our work. 15-17 Results and Discussion The synthesis of new saturated 2-nitrosugar deriva- tives (11-20, 22) takes place by addition of m-CPBA to a chloroform refluxing solution of the corresponding 2-aminosugar (1-10, 21) (Schemes 1 and 2). The X Abstract published in Advance ACS Abstracts, September 1, 1997. (1) (a) Wade, P. A.; Giuliano, R. M. Organic Nitro Chemistry Series; Nitro Compounds, Feuer, H., Neilson, A. T., Eds.; VCH Publishers, Inc.; West Lafayette, 1990; Chapter 2, pp 137-265. (b) Hauser, F. M.; Ellenberger, S. R. Chem. Rev. 1986, 86, 35-67. 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Commun. 1988, 18, 97-114. (13) Nysted, L. N.; Burtner, R. R. J. Org. Chem. 1962, 27, 3175- 3177. (14) Robinson, C. H.; Milewich, L.; Hofer, P. J. Org. Chem. 1966, 31, 524-528. (15) Vega-Pe ´rez, J. M.; Espartero, J. L.; Ruiz, F. J.; Alcudia, F. Carbohydr. Res. 1992, 232, 235-247. (16) Iglesias-Guerra, F.; Candela, J. I., Espartero, J. L.; Vega-Pe ´rez, J. M. Tetrahedron Lett. 1994, 35, 5031-5034. (17) Vega-Pe ´ rez, J. M.; Candela, J. I., Vega, M.; Alcudia, F.; Iglesias- Guerra, F. J. Mass Spectrom. 1996, 31, 493-499. Scheme 1 6608 J. Org. Chem. 1997, 62, 6608-6611 S0022-3263(97)00713-5 CCC: $14.00 © 1997 American Chemical Society