Dedicated to Prof. Dr. Anronio G6mez-Sbnchez on the occasion of his 65th birthday.(5.1X.9 1) Diazo transfer from trifluoromethanesulfonyl azide (TfN,) to 2-amino-2-deoxy-glycoses constitutes a high-yielding, simple procedure for the preparation of partially protected or unprotected 2-azido-2-deoxy-aldoses. Thus, the o-allosamine derivative 2 gave 93% of 3, while diazo transfer to o-glucosamine, o-mannosamine, and o-galactosamine, followed by acetylation, yielded the azides 5, 7, and 9 in yields of 74-91, 65, and 70%, respectively.Introduction. -The 2-Azido-2-deoxy derivatives of mono-and disaccharides are frequently used intermediates in the synthesis of amino-deoxy oligosaccharides (see [ 11 for leading ref.). These azides have been prepared by azidonitration of glycals [2], by addition of halogeno azides to glycals [3], and from 1,6-anhydroglycoses either by opening of epoxides [4] or by substitution of 2-0-triflates [5]. The diastereoselectivity of the azidonitration and halogeno-azide addition depends on the configuration of the glycal. It is high for the lyxo-glycals, leading to mixtures of 2-azido-2-deoxy-galactose nitrates

Dedicated to Duilio Arigoni on the occasion of his 65th birthday (1.X.93)In the context of the hypothesis postulating a heterolytic cleavage of a C-N bond during thermolysis of alkoxydiazirines (Scheme I ) , we report the preparation of the diazirines4,5,7, and 8, the kinetic parameters for the thermolysis in MeOH of the diazirines 1 and 4-9, and the products of their thermolysis in an aprotic environment. The diazirines 4,5,7, and 8 (Schemes 2-5) were prepared from the known hemiacetals 10,19,34 (prepared from 31 in an improved way), and 42 according to an established method. The oximes 11,20,35, and 43 were obtained from the corresponding hemiacetals as (E/Z)-mixtures; 43 was formed together wlth the cyclic hydroxylamine 44. Oxidation of 11,35, and 43 (N-chlorosuccinimide/l,8-diazabicyclo[5.4.0]undec-7-ene (NCS/DBU) or NaIO,) gave good yields of the (Z)-hydroximolactones 12, 36, and 45, while the oxime 20 led to a mixture of the (E)-and (2)-hydroximolactones 21 and 22, which adopt different conformations. Their configuration was assigned, inter alia, by a comparison with the enol ethers 28 and 29, which were obtained, together with 30, from the reaction of the diazirine 5 with benzaldehyde and PBu,. Treatment of the hydroximolactone 0-sulfonates 13,23,37, and 46 with NH,/MeOH afforded the diaziridines 15,25,38, and 47 in good yields, while the (E)-sulfonate 24 decomposed readily. Oxidation of the diaziridines gave 4, 5, 7, and 8, respectively. Thermolysis of the diazirines 1 and 4-9 in MeOH yielded the anomeric methyl glycosides 50/51,16/17,26/27,52/53,39/40,48/49, and 54/55, respectively. A comparison of the kinetic data of the thermolysis at four different temperatures shows the importance of conformational and electronic factors and is compatible with the hypothesis of a heterolytic cleavage of a C-N bond. An early transition state is evidenced by the absence of torsional strain by an annulated 1,3-dioxane ring. Thermolysis of 1 in MeCN at 23" led mostly to the diastereoisoineric (Z,Z)-, (E,E)-, and (E,Z)-lactone azines 56, 57, and 58 (Scheme 6), which convert to 56 under mild conditions, and to 59 (3%). The benzyloxyglucal59 was obtained in higher yields (IS%), together with 44% of 5658, by thermolysis of solid 1. Similarly, thermolysis at higher temperatures of4 in toluene, THF, or dioxane and of 9 in CH2C12 or THF yielded the (Z,Z)-lactone azines 60 and 61, respectively, the latter being accompanied by the dihydro-oxazole 62.Introduction. -Diazirines [I] are important precursors of carbenes, and the mechanism of their thermolysis attracted considerable attention, which focused on the concertedness of the cleavage of the two C-N bonds and the homo-or heterolytic nature of the bond breaking [2-71. The mechanism and the kinetics of the thermolysis of (a1koxy)alkyldiazirines (see [8] and earlier papers of the series [9-131) have not been studied, but we hypothesized that thermolysis of 1-azisugars, such as 1, i.e. cyclic (alkoxy)alkyldiazirines, is initiated by heterolysis of one of the C( 1)-N bonds, accord-

The synthesis of the first glycosylidene-derived 2-acetamido-2-deoxydiazirine 4 from N-acetylglucosamine 6 is described. Thus, 6 was transformed into the 3-0-mesylglucopyranoside 9 by glycosidation with ally1 alcohol, benzylidenation, and mesylation (Scheme 2). Solvolysis of 9 gave the allopyranoside 10 which, upon benzylation and glycoside cleavage, yielded the hemiacetals 12. Using our established method (via the lactone oxime 14 and the diaziridines 16), 12 gave the diazirine 4. Thermolysis of this diazirine in the presence of i-PrOH gave the dihydro-l,3-oxazole 5 (Scheme 1); in the presence of acrylonitrile, the four diastereoisomeric spirocyclopropanes 17-20 and the acetamidoallal 21 were obtained and separated by prep. HPLC (Scheme 3). Assignment of the configuration of 17-20 is based on NOE measurements and on the effect of diamagnetic anisotropy of the CN group. The ratio of the four cyclopropanes, which is in keeping with earlier results, is rationalized.Introduction. -The glycosylidene-derived diazirine 1 [la] is a precursor of the glycosylidene carbene 2, which formally inserts into the 0-H bond of phenols [ lb][2] and alcohols [la] to give glycosides 3 (Scheme I ) . The available evidence shows that the formal insertion into acidic 0-H bonds is initiated by a proton transfer to the intermediate carbene 2, leading to a tight ion pair, whilst the insertion into the 0-H bond of less acidic alcohols, such as i-PrOH, occurs either by aconcerted process or via an ylide. Preliminary experiments have shown that the 2-acetamido-2-deoxyallose-derived diazirine 4, prepared in the context of the synthesis of allosamidin [3], reacts with i-PrOH to form the dihydro-1,3-0xazole 5 as the main product (Scheme 1). Such dihydrooxazoles are typically formed by the neighboring group participation of the acetamido group during SNl type substitutions at the anomeric center. As the glykosidation of i-PrOH by 1 appears not to proceed by an initial protonation of 2, one has to consider a direct or indirect participation of the acetamido group of 4 in the protonation of the corresponding carbene. The diazirine 1 also reacts thermally or under photolytic conditions with acceptor-substituted alkenes to yield cyclopropanes [4]'). To investigate, if the presence of an acetamido group is compatible with the formation of cyclopropanes, we have examined the reaction of 4 with acrylonitrile. In the following, we report the synthesis of the aziallose 4, the experimental details of its reaction with i-PrOH, and the results of its cyclopropane formation using acrylonitrile under thermal conditions.

Glycosylidene carbenes derived from the GlcNAc and AllNAc diazirines 1 and 3 were generated by thermolysis or photolysis of the diazirines. The reaction of 1 with i-PrOH gave exclusively the isopropyl (x -D-glycoside of 5 besides some dihydrooxazole 9 (Scheme 2). A similar reaction with (CF,),CHOH yielded predominantly the ix -D-anomer of 6, while glycosidation of 4-nitrophenol (+7) proceeded with markedly lower diastereoselectivity. Similarly, the do-diazirine 3 gave the corresponding glycosides 12-14, but with a lower preference for the ix -D-anomers (Scheme 3 ) . The reactions of the carbene derived from 1 with Ph,COH (+ 8) and diisopropylideneglucose 10 (+ 11) gave selectively the (x -D-anomers (Scheme 2). The c( +-selectivity increases with increasing basicity (decreasing acidity) of the alcohols. It is rationalized by an intermolecular H-bond between the acetamido group and the glycosyl acceptor. This H-bond increases the probability for the formation of a 1,2-cis-glycosidic C-0 bond. The gluco-intermediates are more prone to forming a N-H.-.(H)OR bond than the ah-isomers, since the acetamido group in the N-acetylallosamine derivatives forms an intramolecular H-bond to the cis-oriented benzyloxy group at C(3), as evidenced by J/Tand S / c experiments.

N-(4-Nitrophenyl)oxamic acid 1, N-(2-fluoro-4-nitrophenyl)oxarnic acid 7, N-(4-nitrophenyl)-trifluoroacetamide 3, and N-(2-methoxy-4-nitrophenyl)trifluoroacetamide 9 are non-competitive inhibitors of Vibrio cholerae sialidase with Ki-values ranging from 2.66 to 5.18 . 10-4 M. These compounds, and the Nacetylneuraminic-acid analogues 11-13 do not inhibit the sialidase and trans-sialidase activities from Trypanosomu cruzi; nor does N-(4-nitrophenyl)oxamic acid (1) inhibit the corresponding enzyme activities from T. brucei.