Anomeric Spirocycles by Solvent Incorporation: Reactions of O-Peracylated (Glyculopyranose and Glyculopyranosyl Bromide)onamide Derivatives with Ketones

Our reference: CAR 6720 P-authorquery-v11 AUTHOR QUERY FORM Journal: CAR Article Number: 6720 Please e-mail or fax your responses and any corrections to: E-mail: [email protected] Fax: +31 2048 52799 Dear Author, Please check your proof carefully and mark all corrections at the appropriate place in the proof (e.g., by using on-screen annotation in the PDF file) or compile them in a separate list. Note: if you opt to annotate the file with software other than Adobe Reader then please also highlight the appropriate place in the PDF file. To ensure fast publication of your paper please return your corrections within 48 hours. For correction or revision of any artwork, please consult http://www.elsevier.com/artworkinstructions. Any queries or remarks that have arisen during the processing of your manuscript are listed below and highlighted by flags in the proof. Click on the ‘Q’ link to go to the location in the proof. Location in article Query / Remark: click on the Q link to go Please insert your reply or correction at the corresponding line in the proof Q1 Please confirm that given name(s) and surname(s) have been identified correctly. Q2 Please check the sentence ‘As...tried’ for clarity, and correct if necessary. Q3 Please check the usage of the term ‘splitted resonances’ in the sentence ‘Proton...3)’, and correct if necessary. Q4 Please provide publisher details for Ref. 16. Q5 Please specify the significance of footnote ‘⁄’ cited in Table 1, as a corresponding footnote text has not been provided. Thank you for your assistance. Please check this box if you have no corrections to make to the PDF file Graphical abstract pp xxx–xxxAnomeric spirocycles by solvent incorporation: reactions of O-peracylated (glyculopyranose and glyculopyranosyl bromide)onamide derivatives with ketones András Páhi, Katalin Czifrák, Katalin E. Kövér, László Somsák * O Br CONH 2 (AcylO) n O OH CONH 2 (AcylO) n O (AcylO) n O OO (AcylO) n OO R 1 R 2 R 1 R 2 HN NH O (AcylO) n ONH R 1 R 2 O R 1 R 2 O (as solvent) Ag(I) salt R 1 R 2 O (5 equiv or as solvent) H + + major minor configurations: D -gluco, D -galacto CAR 6720 No. of Pages 1, Model 5G 13 April 2014 Highlights Ketone incorporation reactions. Preparation of glycopyranosylidene-spiro-(4-imino-1,3-dioxolanes). Preparation of glycopyranosylidenespiro-(oxazolidin-4-ones). 1 Anomeric spirocycles by solvent incorporation: reactions of O-peracylated (glyculopyranose and glyculopyranosyl bromide) onamide derivatives with ketones András Páhi a ,Katalin Czifrák a ,Katalin E. Kövér b ,László Somsák a, ⇑ a Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary 10 b Department of Inorganic and Analytical Chemistry, University of Debrecen, POB 21, H-4010 Debrecen, Hungary article info Article history: Received 13 March 2014 Received in revised form 31 March 2014 Accepted 1 April 2014 20 Available online xxxx Keywords: Solvent incorporation Spiro compounds Anomeric spirocycles 4-Imino-1,3-dioxolanes Oxazolidin-4-ones abstract Reactions of O-peracetylated ( a -D-galacto-heptulopyranosyl bromide)onamide and O-perbenzoylated ( a -D-gluco-heptulopyranosyl bromide)onamide with ketones in the presence of silver(I) salt promoters gave the corresponding O-peracylated 1 0 ,5 0 -anhydro-D-glycitol-spiro-[1 0 ,5]-4-imino-2,2-disubstituted1,3-dioxolanes. The D-galacto configured starting compounds furnished both spiro epimers, while the D-gluco counterparts yielded only configurationally inverted products. Under acidic conditions, O-perbenzoylated a -D-gluco-heptulopyranosonamide and ketones yielded the protected 1 0 ,5 0 -anhydroD-glucitol-spiro-[1 0 ,5]-2,2-disubstituted-oxazolidin-4-ones, which were O-debenzoylated by the Zemplén protocol. These compounds had no inhibition against rabbit muscle glycogen phosphorlyase b. Ó2014 Published by Elsevier Ltd. 1. Introduction Spirocyclic motifs are widespread among natural products and synthetic compounds, and often exhibit interesting and useful biological activities. 1–3 Spirocycles involving the anomeric carbon of monosaccharide derivatives are also well known, and have been, among others, shown to possess antiparasitic, 4 antibacterial, antifungal, 5 antidiabetic, 6 herbicide, 7 glycosidase 8–10 and glycogen phosphorylase 11 inhibitory activities. Synthetic strategies to obtain spirocycles were amply 50 reviewed, 1–3 and ring closure of geminally disubstituted cyclic compounds were highlighted as one of several generally applied approaches towards various spiro derivatives. Following this principle for the preparation of anomeric spirocycles the necessary starting compounds can be selected from monosaccharides homoor heterobifunctionalized at the anomeric centre. 1 The latter type precursors are represented among others by derivatives of ulose type sugars utilized, for example, for the syntheses of many sorts of spironucleosides. 12 In this line we reported the transformations of (glyculopyranosyl bromide)onic acid derivatives 13 60to glycopyranosylidene-spiro-(thio)hydantoins, 14,15 -thiazolidinones, 16 and -oxazolines, 17 as well as that of (glyculopyranosyl thiocyanate)ononitriles to glycopyranosylidene-spiro-thiazolines. 18 Some years ago we observed that on generation of the corresponding glycosylium ion from (glyculopyranosyl bromide)onamides (e.g., 1)by Ag 2 CO 3 in acetone spiro-imino-dioxolanes 2a and 3a (Table 1) were formed by incorporation of the solvent. 19 This reaction can be regarded as a direct O-glycosylation of a ketone which is a very rare transformation: formation of acetal glycosides in the presence of ketones was described from O-peracety70 lated N-(2,4-dinitrophenyl)- a - D -glucosaminyl bromide (but not from acetobromoglucose), 20 TMS-glycosides 21,22 and O-perbenzylated 1-thioglycosides. 23 Formal glycosylation of ketones by a special intramolecular aglycon delivery was recently reported. 24 In this paper full experimental details are reported for the extension of the above ketone incorporation in reactions of (glyculopyranosyl bromide)onamides. Furthermore, studies on the reactions of (glyculopyranose)onamides and ketones as well as detailed structural elucidation of the compounds are also described. 80 2. Results and discussion Following the first observation 19 on incorporation of acetone into the products in the reaction of 1(Table 1,entry 1) in the presence of Ag 2 CO 3 , the applicability of other ketones and promoters http://dx.doi.org/10.1016/j.carres.2014.04.003 0008-6215/Ó2014 Published by Elsevier Ltd. ⇑ Corresponding author. Tel.: +36 52512900x22348; fax: +36 52512744. E-mail address: [email protected] (L. Somsák). 1 Strictly speaking these compounds might no more have a ‘real’ anomeric, that is, an acetal type carbon in many cases, however, for the sake of simplicity this term will be used here. Q1 Carbohydrate Research xxx (2014) xxx–xxx Contents lists available at ScienceDirect Carbohydrate Research journal homepage: www.elsevier.com/locate/carres CAR 6720 No. of Pages 11, Model 5G 15 April 2014 Please cite this article in press as: Páhi, A.; et al. Carbohydr. Res. (2014), http://dx.doi.org/10.1016/j.carres.2014.04.003 were investigated. With butanone both Ag 2 CO 3 and AgOTf gave similar results (entries 2 and 3) expectedly furnishing the spirodioxolanes 2b and 3b as inseparable diastereomeric mixtures. Symmetrical ketones (entries 4–6) also gave the spiro-epimers 2c–e as the main products whereby 3c–e could be isolated in much lower yields. From each reaction mixture the hydrolytic product 4 90 could be isolated in 25–38% yields. Similar reactions of the D -gluco configured 5are collected in Table 2. Comparisons of entries 1, 3and 5 with entries 2, 4and 6, respectively, show that the use of AgOTf is superior to that of Ag 2 CO 3 in terms of reaction times, although the higher efficiency of the former is not always reflected in the yields. In these reactions of 5only spiro-epimer 6was observed in the reaction mixtures (besides the hydrolyis product 7). Attempts to reduce the amount of the ketones to 5–10 equiv in nitromethane as the solvent proved unsuccesful, and the only 100 products to be observed were 4and 7. Trials to use aldehydes as the carbonyl reagents resulted in multicomponent mixtures from which no discrete products could be isolated. Reactions of ( D -gluco-hept-2-ulopyranose)onamide 7with ketones were investigated next (Table 3). As in similar cyclizations of non-carbohydrate a -hydroxy-carboxamides p-toluenesulfonic acid (pTSA) was frequently applied to promote the transformation 25 this acid was tried first. However, no reaction of 7could be observed with acetone as the solvent in the presence of either catalytic or stoichiometric amounts of pTSA. On the other hand, 110 catalytic triflic acid (TfOH) elicited the reaction (entry 1), and raising its amount to one equivalent significantly increased the yield of 8a (entry 2). Under the same conditions butanone gave an inseparable diastereomeric mixture of 8b (entry 3). The amount of the ketone could be diminished to 5 equiv, and both THF and toluene proved suitable solvents to prepare 8c–f in good yields (entries 4–7). In these reactions formation of one compound was observed in each case (disregarding diasteromers 8b). Reactions with aldehydes gave only decomposition products. Spiro-oxazolidinones 8were O-debenzoylated by the Zempén 120 protocol to give compounds 9in very good yields. These derivatives were tested as possible inhibitors of rabbit muscle glycogen phosphorylase b, however, showed no inhibition up to 625 l M concentration. Structural elucidation of the products (following the mass spectrometric determination of the molecular masses) was carried out by NMR methods as illustrated for the compounds depicted in Figure 1(see also Table 4 for selected NMR data of the compounds). Proton spectra showed splitted resonances for a pyranoid ring in the 4 C 1 conformation as well as the expected signals of the ali130 phatic parts and the presence of an exchangable proton assigned as an NH for each compound (see details in Section 3). The carbon spectra contained (besides the expected resonances for the sugar ring, the acyl protecting groups and the aliphatic moieties) signals for three carbons with no attached hydrogens. Those in the range of 99.9–100.7 ppm were assigned as the C-[1 0 ,5] spiro centres. Resonances of 112.5–122.2 and 158.2–160.9 ppm (clearly distinct from the C@Oresonances of the protective groups) were indicative of acetal and imidate type carbons, respectively, in compounds 2,3 and 6. On the contrary, the spectra of compounds 8exhibited Table 1 Reaction of O-peracetylated ( a -D-galacto-heptulopyranosyl bromide)onamide (1) with ketones O AcO AcO AcO OAc Br CO 1234 NH2 O AcO AcO AcO OAc O OO AcO AcO AcO OAc OO O AcO AcO AcO OAc OH CONH2 HN NH R1 R2 R1R2 R1R2 O as solvent promoter ++ (1 equiv.) in the dark, under Ar rt Entry R 1 R 2 Promoter R. time (d) Yield (%) 1a a Me Me Ag 2 CO 3 17145 2bMe Et Ag 2 CO 3 649 bc c 3 AgOTf 6 43 b 19 ⁄ 38 4cEt Et AgOTf 3 32 14 27 5d–(CH 2 ) 4 – AgOTf 6 48 Traces 26 6e–(CH 2 ) 5 – AgOTf 2 44 8 25 a From Ref. 19. b Two diastereomers. c Observed but not isolated. Table 2 Reaction of O-perbenzoylated ( a -D-gluco-heptulopyranosyl bromide)onamide (5) with ketones O BzO BzO BzO OBz Br CONH 2 R 1 R 2 O as solvent 1 equiv. promoter in the dark, under Ar rt O BzO BzO BzO OBz O O HN R 1 R 2 O BzO BzO BzO OBz OH CONH 2 + 567 Entry R 1 R 2 Promoter R. time (d) Yield (%) 1aMe Me Ag 2 CO 3 11 17 41 2 AgOTf 1 37 46 3cEt Et Ag 2 CO 3 20 5 34 4 AgOTf 1 46 35 5d–(CH 2 ) 4 –Ag 2 CO 3 13 56 18 6e–(CH 2 ) 5 – AgOTf 1 28 35 Q5 Q2 Q3 2A. Páhi et al. / Carbohydrate Research xxx (2014) xxx–xxx CAR 6720 No. of Pages 11, Model 5G 15 April 2014 Please cite this article in press as: Páhi, A.; et al. Carbohydr. Res. (2014), http://dx.doi.org/10.1016/j.carres.2014.04.003 140 an additional signal in the range of the benzoyl carbonyls (162.4– 166.6 ppm) and from these that of the highest chemical shift was (tentatively) assigned to amide C-4. A resonance in the range of 92.4–100.1 ppm could be attributed to an aminal type carbon and this corroborated that the nitrogen was in an endocyclic position in 8. To confirm the difference in the constitution of the heterocyclic parts of the spirocycles, CMPG-HSQMBC experiments 26– 28 were carried out with 6a and 8e. In these spectra cross peaks (indicated by asterisks in the formulae of the respective compounds in Fig. 1) between NH and C-4 and C-5, but not with C-2, 150 were observed for 6a to further prove the imino-dioxolane structure. On the other hand, cross peaks between NH and C-2, C-4 and C-5, as well as with carbons of the aliphatic substituent were present for 8e to verify the oxazolidinone ring. For 8e this measurement also corroborated the chemical shift assignment of amide C-4. The configuration of the spiro carbons C-[1 0 ,5] was established as Rfor 2and 6, and Sfor 3and 8based on the three bond heteronuclear coupling constants between H-2 and C-4 shown in Figure 1indicating the trans diaxial versus gauche relationships between the respective nuclei in the 4 C 1 conformation 160 of the sugar ring. Although these couplings could not be measured for each compound due to insufficient sample quantities, no doubt was left about the spiro configuration of the other members of the series. Namely, the proton resonances had characteristic shifts depending on the C-[1 0 ,5] configuration (cf. Fig. 1 and Table 4): H-2 0 had a downfield shift of 0.1–0.2 ppm if the C@NH/C@O was on the same side of the pyranoid ring; similarly, downfield shifts were observed for H-3 0 (0.7 ppm) and H-5 0 (0.4 ppm) when they were in the same situation. Analogous 1 H chemical shift patterns were observed earlier for other glycopyranosylidene170 spiro-heterocycles. 14,15 Formation of spirocycles 2,3and 6can be understood by following the mechanistic proposal in Scheme 1. The silver salt promoter facilitates the generation of the corresponding glycosyliumion B1 from 1or 5. Nucleophilic attack of a ketone with anchimeric assistance of the 2-O-acyl group (D1) may lead to carbocation A1 while without neighbouring group participation the epimeric cation, represented by resonance forms E1 and F1, can be formed. Intramolecular attack of the amide oxygen (illustrated in details for F1 only), the harder part of this functional group, H-5' O O O AcO AcO OAc HN Et Et H-3' H-2' AcO H-5' O O O AcO AcO OAc H-3' H-2' AcO NH Et Et 3JH-2',C-4 ~6.1Hz 3JH-2',C-4 ~2.1Hz 160.4 160.8 116.8 99.9 100.8 116.2 5.99 4.85 5.60 5.30 4.42 5.74 H-5' O O O BzO BzO OBz HN Me Me H-3' H-2' BzO 3JH-2',C-4 ~5.4Hz 160.5 112.8 100.3 6.80 5.13 5.85 H-5' O O NH BzO BzO OBz H-3' H-2' BzO O 3JH-2',C-4 ~2.5Hz 166.4 6.10 4.69 6.00 ** ** * * * ** * Cross peaks with NH in the spectra from CPMG-HSQMBC experiments. 100.1 93.5 37.6 (39.0) 39.0 (37.6) 2c 3c 6a 8e 2 4 4 2 2 4 4 2 1' 55 1' 1' 5 1' 5 Figure 1. Representative NMR data for the structural elucidation of the new compounds. Table 3 Reaction of 3,4,5,7-tetra-O-benzoyla -D-gluco-heptulopyranosonamide (5) with ketones O BzO BzO BzO OBz OH CONH 2 R 1 R 2 O O BzO BzO BzO OBz ONH /TfOH solvent, reflux overnight O R 2 R 1 O HO HO HO OH ONH O R 2 R 1 NaOMe MeOH, rt 78 9 Entry R 1 R 2 Ketone (equiv.) Solvent Acid (equiv.) Yield (%) 1aMe Me As solvent — 0.1 58 94 2 As solvent — 1.0 89 3bMe Et As solvent — 1.0 92 a 96 4cEt Et 5 THF 1.0 69 91 5d–(CH 2 ) 4 – 5 THF 1.0 86 91 6e–(CH 2 ) 5 – 5 Toluene 1.0 69 96 7f–(CH 2 ) 6 – 5 Toluene 1.0 71 77 a Two diastereomers. A. Páhi et al. / Carbohydrate Research xxx (2014) xxx–xxx 3 CAR 6720 No. of Pages 11, Model 5G 15 April 2014 Please cite this article in press as: Páhi, A.; et al. Carbohydr. Res. (2014), http://dx.doi.org/10.1016/j.carres.2014.04.003 180 may give the cyclized iminium ion C1. Deprotonation of this intermediate and that of the analogous one (not shown) derived from A1 give then the isolated products of retained (3) and inverted configuration (2), respectively. Formation of the by-products 4and 7 are to be explained by the water content of the solvents attacking on glycosyliumion B1. The finding that from the D -gluco configured 5only the formation of 6was observed, 2 while 1of the D-galacto configuration gave both epimers 2and 3, may be indicative of a remote participation 29 of the axial 4-O-acetyl group of 1facilitating the formation of 3. 190 A mechanistic proposal for the formation of spirocycles 8 (Scheme 2) can be more complex since, due to the presence of several functional groups whose protonation may start the reaction, alternative pathways may occur simultaneously. The first (most tempting) possibility is the protonation of the glycosidic OH in 7 followed by loss of water to give glycosyliumion C2 which is the same intermediate as B1 in Scheme 1. Attack of a ketone on C2 would give A2 (equal to intermediate F1 in Scheme 1), however, the formation of the epimeric intermediate A1 (shown in Scheme 1) must also be taken into account. This possibility renders this path200 way less probable since only the configurationally retained epimer 8was observed in the reactions. Formation of A2 (without epimerization) should also be possible via protonation and subsequent dehydration of a mixed hemiketal E2 which can develop from 7 by nucleophilic addition of the glycosidic OH to the ketone or its protonated form D2. Ring closure of A2 (=F1) occurred by the nucleophilic attack of the amide oxygen under conditions of Scheme 1 (cf. F1?C1) to give the imino-dioxolanes 3, however, these compounds were not present in the reactions of 7(Scheme 2). Considering the different reaction conditions this may raise 210 two possibilities: (i) imino-dioxolanes may be formed as primary Table 4 Selected NMR data for the O-peracylated compounds a 2,3,6and 8(d[ppm], J[Hz]) O AcO AcO AcO OAc O O HN R 1 R 2 1' 2' 3' 4' 5' 2 4 5 2a b 2b 2c 2d 2e H-2 0 5.58 5.54/5.59 5.60 5.57 5.57 H-3 0 6.00 6.05/5.89 5.99 5.98 6.01 H-5 0 4.88 4.75/4.85 4.85 4.84 4.85 C-[1 0 ,5] 100.4 100.2/100.3 99.9 100.1 100.1 C-2 112.6 114.7/114.1 116.8 116.2 113.2 C-4 160.9 160.4/160.2 160.4 158.8 158.2 3 J H-2 0 ,C-4 5.6 4.1 6.1 6.1 5.3 O AcO AcO AcO OAc OO NH R1R2 1' 2' 3' 4' 5' 2 4 5 3a b 3b 3c 3e H-2 0 5.74 5.74/5.69 5.74 5.75 H-3 0 5.25 5.35/5.20 5.30 5.26 H-5 0 4.41 4.43/4.39 4.42 4.41 C-[1 0 ,5] 100.3 100.9/100.9 100.8 100.8 C-2 112.5 114.8/113.8 116.2 113.1 C-4 161.2 160.2/160.2 160.8 160.3 3 J H-2 0 ,C-4 n.m. c n.m. c 2.1 n.m. c O BzO BzO BzO OBz O O HN R 1 R 2 1' 2' 3' 4' 5' 2 4 5 6a 6c 6d 6e H-2 0 5.85 5.92 5.87 5.87 H-3 0 6.80 6.82 6.82 6.82 H-5 0 5.13 5.13 5.12 5.14 C-[1 0 ,5] 100.3 99.9 99.9 99.8 C-2 112.8 116.6 122.2 113.5 C-4 160.5 160.6 160.3 160.4 3 J H-2 0 ,C-4 5.4 4.9 4.9 5.0 O BzO BzO BzO OBz ONH O R2 R1 1' 2' 3' 4' 5' 2 5 4 8a 8b 8c 8d 8e 8f H-2 0 5.96 5.99/5.97 6.00 5.97 6.00 5.98 H-3 0 6.09 6.10/6.09 6.10 6.08 6.10 6.08 H-5 0 4.66 4.63/4.63 4.64 4.63 4.69 4.66 H-4 0 5.73 5.72/5.71 5.70 5.73 5.71 5.70 C-[1 0 ,5] 100.5 100.3/100.35 100.2 100.7 100.1 100.1 C-2 92.4 94.9, 94.5 97.1 100.1 93.5 97.2 C-4 166.0 166.4/166.1 166.6 166.1 166.4 166.1 3 J H-2 0 ,C-4 n.m. c n.m c n.m c n.m. c 2.5 n.m. c a For substituents R 1 and R 2 see the respective tables (Table 1 for 2and 3,Table 2 for 6, and Table 3 for 8). b Data taken from Ref. 19. c Not measured because of insufficient sample quantity. 2 It is to be noted that from the acetylated counterpart of 5formation of a very minor amount (6%) of the inverted product was reported. 19 4A. Páhi et al. / Carbohydrate Research xxx (2014) xxx–xxx CAR 6720 No. of Pages 11, Model 5G 15 April 2014 Please cite this article in press as: Páhi, A.; et al. Carbohydr. Res. (2014), http://dx.doi.org/10.1016/j.carres.2014.04.003 products which then give oxazolidinones 8in a proton catalysed equilibration; (ii) ring closure takes place by a N-nucleophilic attack of the hydroximide tautomer of the amide moiety. The first possibility was ruled out by an experiment in which an iminodioxolane 6was subjected to the conditions of the formation of 8. Thus, 6a was boiled in acetone in the presence of TfOH (1 equiv) for 24 h, however, no change could be detected by TLC. The second possibility can be reasonable since tautomerization of amides under acidic conditions (cf. 7?F2?I2) is a known phenomenon. 30 220 Thus, A2 may ring-close to protonated hydroxy-oxazoline B2 which, after deprotonation and tautomerization can give the isolated 8. OCONH2 Br RCO O O CONH2 RCO O OCONH2 RCO O O CONH2 O O R O CONH2 RCO O O RCO O NH2 O C1 B1A1 D1 E1 F1 Ag -AgBr R1R2 O O R1R2 O R1R2 O RCOOO NH R1R2 O O RCOOO NH2 R1R2 O -H R2 R1 O R2 R1 O O ROCO O O HN R1 R2 R1R2 O R1R2 O Ag / Ag / 1or 5 2or 63 OCONH2 OH RCO O 4or 7 H2O Ag H2O Scheme 1. Proposed mechanism for the formation of 1 0 ,5 0 -anhydroD -glycitol-spiro-[1 0 ,5]-4-imino-1,3-dioxolanes 2,3, and 6. O CONH2 RCO O C2 (= B1 in Scheme 1) OCONH2 OH RCO O H O RCOONH O R1R2 O R1R2 OH O OH RCO O OH NH2 O OH RCO O OH NH R1R2 O O OH RCO O OH N H-H2O HO R2 R1 -H O RCOO HO N OH R1R2 -H tautomerisation 78 F2 H2 I2 J2 O RCO O OH N HO R2 R1 G2 O OH RCO O OH N R2 R1 K2 H -H2O + H -H2O OCONH2 O RCO O R1R2 OH OH R1R2 -H R1R2 O H -H2O O RCO O OH NH A2 (= F1 in Scheme 1, cf A1 also) O R1R2 O RCOONH OH R1R2 O -H tautomerisation B2 E2 D2 Scheme 2. Possible mechanistic pathways for the formation of 1 0 ,5 0 -anhydroD -glucitol-spiro-[1 0 ,5]-oxazolidin-4-ones 8. A. Páhi et al. / Carbohydrate Research xxx (2014) xxx–xxx 5 CAR 6720 No. of Pages 11, Model 5G 15 April 2014 Please cite this article in press as: Páhi, A.; et al. Carbohydr. Res. (2014), http://dx.doi.org/10.1016/j.carres.2014.04.003 Since a -hydroxy-carboxamides and carbonyl compounds are known to furnish oxazoles under acidic conditions, the generally accepted mechanism of the Fischer oxazole synthesis 25 should also be considered in the present transformation. Protonation of the amide oxygen of 7as shown in F2 may result in a tautomerization 30 to give at least a minor proportion of I2 which can attack the ketone (or its protonatedformD2) as a N-nucleophileto giveintermediate J2.Pro230 tonationofahydroxylgroupinJ2 mayleadtoeliminationofwaterto produce either carbocation G2 or K2, both of which can ring close to H2 by the nucleophilic attack of the remaining OH on the positively charged carbon. Due to the presence of three electron releasing substituents, carbocation K2 might be more stable than glycosyliumion G2, therefore, formation of H2 via K2 might be preferred. This is also madelikely by the formationofa single isomer of8that would probably not be the case in route J2?G2?H2. Final deprotonation and tautomerization of H2 may then yield the isolable product 8. Inconclusion, thereactions of(glyculopyranoseandglyculopyrano240 syl bromide)onamides with ketones gave access to the preparation of new anomeric spirocycles, namely, 1 0 ,5 0 -anhydroD -glycitolspiro-[1 0 ,5]-4-imino-2,2-disubstituted-dioxolanes and 1 0 ,5 0 -anhydroD -glycitol-spiro-[1 0 ,5]-2,2-disubstituted-oxazolidin-4-ones. The structures were unambiguously assigned by NMR methods. Detailed mechanisms were proposed to explain the formation of both constitutional isomers as well as the stereoselectivities of the ring forming reactions. The spiro-oxazolidinones were tested against rabbit muscle glycogen phosphorlyase b, however, had no inhibitory effect. 3. Experimental 250 3.1. General methods Melting points were measured in open capillary tubes or on a Kofler hot-stage and are uncorrected. Optical rotations were determined with a Perkin–Elmer 241 polarimeter at room temperature. NMR spectra were recorded with Bruker 200 (200:50 MHz for 1 H/ 13 C), Bruker DRX 360 (360:90 MHz for 1 H/ 13 C) or Avance II 500 (500:125 MHz for 1 H/ 13 C) spectrometers. Chemical shifts are referenced to Me 4 Si ( 1 H), or to the solvent signals or DSS in D 2 O ( 13 C). Mass spectra were recorded by a Bruker micrOTOF-Q instrument. TLC was performed on DC-Alurolle Kieselgel 60 F 254 (Merck), 260 and the plates were visualized under UV light and by gentle heating. For column chromatography Kieselgel 60 (Merck, particle size 0.063–0.200 mm) was used. Dichloromethane was distilled from P 4 O 10 and acetone from CaSO 4 ) and stored over 4Å molecular sieves. Organic solutions were dried over anhydrous MgSO 4 and concentrated under diminished pressure at 40–50 °C (water bath). 3.2. General procedure I for the preparation of O-peracylated 1 0 ,5 0 -anhydroD -glycitol-spiro-[1 0 ,5]-4-imino-2,2-disubstituted1,3-dioxolanes 2, 3 and 6 To a solution of an O-peracylated (glyculopyranosyl bro270 mide)onamide 1 31 or 5 32 (0.50 g) in a dry ketone (5 mL) containing molecular sieves (3 Å) Ag 2 CO 3 (1 equiv) or AgOTf/Et 3 N (1 equiv) was added. The mixture was stirred at rt in the dark under Ar atmosphere until TLC (1:1 or 1:2 EtOAc–hexane) showed complete transformationofthestartingmaterial.Thenthemixturewasfilteredona Celite pad and the solvent removed under diminished pressure. The crude product was purified by column chromatography. 3.2.1. (1 0 R,2RS)- and (1 0 S,2RS)-2 0 ,3 0 ,4 0 ,6 0 -tetra-O-acetyl-1 0 ,5 0 - anhydroD -galactitol-spiro-[1 0 ,5]-2-ethyl-4-imino-2-methyl1,3-dioxolanes (2b and 3b) 280 Prepared from 1(0.50 g, 1.10 mmol) and butanone in the presence of AgOTf according to General procedure I (Section 3.2). Column chromatography (1:1 EtOAc–hexane) gave three fractions. Fraction I: 0.21 g (43%) of an inseparable diastereomeric mixture of 2b as a colourless oil; R f = 0.71 (1:1 EtOAc–hexane). Characterization of diastereomer A: 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 7.40 (s, 1H, NH), 6.05 (dd, 1H, J 2 0 ,3 0 11.1 Hz, J 3 0 ,4 0 3.2 Hz, H-3 0 ), 5.54 (d, 1H, J 2 0 ,3 0 11.1 Hz, H-2 0 ), 5.51 (dd, 1H, J 3 0 ,4 0 3.2 Hz, J 4 0 ,5 0 1.0 Hz, H-4 0 ), 4.75 (ddd, 1H, J 5 0 ,6 0 a 6.8 Hz, J 5 0 ,6 0 b 6.3 Hz, J 4 0 ,5 0 1.0 Hz, H-5 0 ), 4.20–4.02 (m, 2H, H-6 0 a, H-6 0 b), 2.15, 2.05, 1.95, 290 1.93 (4s, 12H, OCOCH 3 ), 1.70 (q, 2H, J7.3 Hz, CH 2 CH 3 ), 1.35 (s, 3H, CH 3 ), 0.88 (t, 3H, J7.3 Hz, CH 2 CH 3 ); 13 C NMR (CDCl 3 , 90 MHz): d(ppm) 170.3, 170.0, 169.6, 169.3 (CO), 160.4 (C-4, 3 J H2 0 ,C-4 =4.1 Hz), 114.7 (C-2), 100.2 (C-1 0 ), 69.8, 68.8, 67.5, 66.9 (C2 0 –C-5 0 ), 61.3 (C-6 0 ), 33.4 (CH 2 CH 3 ), 25.6 (CH 3 ), 20.7, 20.5, 20.3, 20.2 (COCH 3 ); 6.9 (CH 2 CH 3 ). Characterization of diastereomer B: 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 7.40 (s, 1H, NH), 5.89 (dd, 1H, J 2 0 ,3 0 11.1 Hz, J 3 0 ,4 0 3.2 Hz, H-3 0 ), 5.59 (1H, d, J 2 0 ,3 0 11.1 Hz, H-2 0 ), 5.48 (dd, 1H, J 3 0 ,4 0 3.2 Hz, J 4 0 ,5 0 1.0 Hz, H-4 0 ), 4.85 (ddd, 1H, J 5 0 ,6 0 a 6.8 Hz, J 5 0 ,6 0 b 6.3 Hz, J 4 0 ,5 0 300 1.0 Hz, H-5 0 ), 4.20–4.02 (m, 2H, H-6 0 a, H-6 0 b), 2.16, 2.04, 1.98, 1.94 (4s, 12H, OCOCH 3 ), 1.85 (q, 2H, J7.3 Hz, CH 2 CH 3 ), 1.55 (s, 3H, CH 3 ), 0.96 (t, 3H, J7.3 Hz, CH 2 CH 3 ); 13 C NMR (CDCl 3 , 90 MHz): d(ppm) 170.2, 170.0, 169.8, 169.1 (CO), 160.2 (C-4), 114.1 (C-2), 100.3 (C-1 0 ), 69.9, 68.8, 67.2 (2) (C-2 0 –C-5 0 ), 61.3 (C6 0 ), 32.4 (CH 2 CH 3 ), 25.6 (CH 3 ), 20.8, 20.5, 20.3, 20.1 (OCOCH 3 ), 6.9 (CH 2 CH 3 ). Calcd for C 19 H 27 NO 11 (Mol. Wt.: 445.42, Ex. Mass.: 445.16); ESI-MS (positive mode) m/z:468.148 [M+Na] + , 913.305 [2M+Na] + . Fraction II: 0.10 g (19%) of an inseparable diastereomeric mix310 ture of 3b as a yellowish oil; R f = 0.36 (1:1 EtOAc–hexane). Characterization of diastereomer C: 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 7.48 (s, 1H, NH), 5.74 (d, 1H, J 2 0 ,3 0 11.1 Hz, H-2 0 ), 5.51 (dd, 1H, J 3 0 ,4 0 3.2 Hz, J 4 0 ,5 0 1.0 Hz, H-4 0 ), 5.35 (dd, 1H, J 2 0 ,3 0 11.1 Hz, J 3 0 ,4 0 3.2 Hz, H-3 0 ), 4.43 (ddd, 1H, J 5 0 ,6 0 a 6.8, J 5 0 ,6 0 b 6.3 Hz, J 4 0 ,5 0 1.0 Hz, H-5 0 ), 4.20–4.03 (m, 2H, H-6 0 a, H-6 0 b), 2.10, 2.08, 2.01, 1.98 (4s, 12H, OCOCH 3 ), 1.88 (q, 2H, J7.3 Hz, CH 2 CH 3 ), 1.54 (s, 3H, CH 3 ), 1.00 (t, 3H, J7.3 Hz, CH 2 CH 3 ); 13 C NMR (CDCl 3 , 90 MHz): d(ppm) 170.4, 170.2, 169.8, 169.1 (CO), 160.2 (C-4), 114.8 (C-2), 100.9 (C-1 0 ), 69.7, 68.6, 67.7, 66.5 (C-2 0 –C-5 0 ), 61.7 (C-6 0 ), 32.4 (CH 2 CH 3 ), 320 25.8 (CH 3 ), 20.7, 20.5, 20.2, 20.1 (COCH 3 ); 6.8 (CH 2 CH 3 ). Characterization of diastereomer D: 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 7.48 (s, 1H, NH), 5.69 (d, 1H, J 2 0 ,3 0 11.1 Hz, H-2 0 ), 5.49 (dd, 1H, J 3 0 ,4 0 3.2 Hz, J 4 0 ,5 0 1.0 Hz, H-4 0 ), 5.20 (dd, 1H, J 2 0 ,3 0 11.1 Hz, J 3 0 ,4 0 3.2 Hz, H-3 0 ), 4.39 (ddd, 1H, J 5 0 ,6 0 a 6.8 Hz, J 5 0 ,6 0 b 6.3 Hz, J 4 0 ,5 0 1.0 Hz, H-5 0 ), 4.18–4.02 (m, 2H, H-6 0 a, H-6 0 b), 2.11, 2.09, 1.99, 1.97 (4s, 12H, OCOCH 3 ), 1.86 (2H, q, J7.3 Hz, CH 2 CH 3 ), 1.61 (s, 3H, CH 3 ), 1.26 (t, 3H, J7.3 Hz, CH 2 CH 3 ); 13 C NMR (CDCl 3 , 90 MHz) d(ppm): 170.4, 170.0, 169.9, 169.6 (CO), 160.2 (C-4), 113.8 (C-2), 100.9 (C-1 0 ), 69.7, 67.6, 66.2 (2) (C-2 0 –C-5 0 ), 60.3 (C-6 0 ), 33.5 (CH 2 CH 3 ), 330 24.2 (CH 3 ), 20.7, 20.6, 20.2, 20.1 (COCH 3 ); 7.9 (CH 2 CH 3 ). Calcd for C 19 H 27 NO 11 (Mol. Wt.: 445.42, Ex. Mass.: 445.16); ESI-MS (positive mode) m/z:468.147 [M+Na] + , 913.304 [2M+Na] + . Fraction III: 0.16 g (38%) of 4 14 as a white solid. 3.2.2. (1 0 R)- and (1 0 S)-2 0 ,3 0 ,4 0 ,6 0 -tetra-O-acetyl-1 0 ,5 0 -anhydroD - galactitol-spiro-[1 0 ,5]-2,2-diethyl-4-imino-1,3-dioxolanes (2c and 3c) Prepared from 1(0.50 g, 1.10 mmol) and pentan-3-one with AgOTf according to General procedure I (Section 3.2). Column chromatography (1:1 EtOAc–hexane) gave three fractions. 340 Fraction I: 0.16 g (32%) of 2c as white crystals; mp: 100–102 °C; [ a ] D +37 (c0.90, CHCl 3 ); 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 7.45 (s, 1H, NH), 5.99 (dd, 1H, J 2 0 ,3 0 11.1 Hz, J 3 0 ,4 0 3.7 Hz, H-3 0 ), 5.60 (d, 1H, J 2 0 ,3 0 11.1 Hz, H-2 0 ), 5.50 (dd, 1H, J 3 0 ,4 0 3.7 Hz, J 4 0 ,5 0 1.2 Hz, H-4 0 ), 4.85 (ddd, 1H, J 5 0 ,6 0 a 6.8 Hz, J 5 0 ,6 0 b 6.3 Hz, J 4 0 ,5 0 1.2 Hz, H-5 0 ), 4.17 (dd, 1H, J 6 0 a,6 0 b 11.6 Hz, J 5 0 ,6 0 a 6.8 Hz, H-6 0 a), 4.09 (dd, 1H, J 6 0 a,6 0 b 11.6 Hz, J 5 0 ,6 0 b 6.3 Hz, H-6 0 b), 2.17, 2.06, 2.02, 1.96 (4s, 12H, OCOCH 3 ), 1.87 (q, 2H, J7.3 Hz, CH 2 CH 3 ), 1.72 (q, 2H, J7.3 Hz, CH 26A. Páhi et al. / Carbohydrate Research xxx (2014) xxx–xxx CAR 6720 No. of Pages 11, Model 5G 15 April 2014 Please cite this article in press as: Páhi, A.; et al. Carbohydr. Res. (2014), http://dx.doi.org/10.1016/j.carres.2014.04.003 CH 3 ), 0.96 (t, 3H, J7.3 Hz, CH 2 CH 3 ), 0.88 (t, 3H, J7.3 Hz, CH 2 CH 3 ); 13 C NMR (CDCl 3 , 90 MHz): d(ppm) 170.1 (2), 169.6, 169.2 (CO), 350 160.4 (C-4, 3 J H-2 0 ,C-4 =6.1 Hz from HSQMBC at 125 MHz), 116.8 (C-2), 99.9 (C-1 0 ), 69.7, 68.9, 67.3 (2) (C-2 0 –C-5 0 ), 61.3 (C-6 0 ), 31.2, 29.4 (CH 2 CH 3 ), 20.5, 20.4 (2), 20.2 (COCH 3 ); 7.8, 6.7 (CH 2 CH 3 ). Fraction II: 0.07 g (14%) of 3c as a white crystals, mp: 61–63 °C; [ a ] D +59 (c1.00, CHCl 3 ); 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 7.42 (s, 1H, NH), 5.74 (d, 1H, J 2 0 ,3 0 11.1 Hz, H-2 0 ), 5.51 (dd, 1H, J 3 0 ,4 0 3.2 Hz, J 4 0 ,5 0 1.1 Hz, H-4 0 ), 5.30 (dd, 1H, J 2 0 ,3 0 11.1 Hz, J 3 0 ,4 0 3.2 Hz, H-3 0 ), 4.42 (ddd, 1H, J 5 0 ,6 0 a 6.8 Hz, J 5 0 ,6 0 b 6.3 Hz, J 4 0 ,5 0 1.1 Hz, H-5 0 ), 4.16 (dd, 1H, J 6 0 a,6 0 b 11.6 Hz, J 5 0 ,6 0 a 6.8 Hz, H-6 0 a), 4.11 (dd, 1H, J 6 0 a,6 0 b 11.6 Hz, J 5 0 ,6 0 b 6.3 Hz, H-6 0 b), 2.19, 2.03, 2.01, 1.98 (4s, 12H, 360 OCOCH 3 ), 1.88 (q, 2H, J7.3 Hz, CH 2 CH 3 ), 1.84 (q, 2H, J7.3 Hz, CH 2 CH 3 ), 0.99 (t, 3H, J7.3 Hz, CH 2 CH 3 ), 0.95 (t, 3H, J7.3 Hz, CH 2CH 3 ); 13 C NMR (CDCl 3 , 90 MHz): d(ppm) 170.3 (2), 170.1, 168.6 (CO), 160.8 (C-4, 3 J H-2 0 ,C-4 =2.1 Hz from HSQMBC at 125 MHz), 116.2 (C-2), 100.8 (C-1 0 ), 69.6, 69.2, 67.7, 66.1 (C-2 0 –C-5 0 ), 61.8 (C-6 0 ), 31.6, 29.0 (CH 2 CH 3 ), 20.8, 20.5, 20.3 (2) (COCH 3 ); 8.0, 6.6 (CH 2 CH 3 ); Calcd for C 20 H 29 NO 11 (Mol. Wt.: 459.44, Ex. Mass.: 459.17); ESI-MS (positive mode) m/z:482.163 [M+Na] + , 941.337 [2M+Na] + . Fraction III: 0.12 g (27%) of 4 14 as a white solid. 370 3.2.3. (1 0 R)- and (1 0 S)-2 0 ,3 0 ,4 0 ,6 0 -tetra-O-acetyl-1 0 ,5 0 -anhydroD - galactitol-spiro-[1 0 ,5]-4-imino-1,3-dioxolane-spiro-[2,1 00 ]- cyclopentanes (2d and 3d) Prepared from 1(0.20 g, 0.44 mmol) and cyclopentanone with AgOTf according to General procedure I (Section 3.2). Column chromatography (1:1 EtOAc–hexane) gave three fractions. Fraction I: 0.10 g (48%) of 2d as white crystals; mp: 148–150 °C; [ a ] D +28 (c0.20, CHCl 3 ); 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 7.40 (s, 1H, NH), 5.98 (dd, 1H, J 2 0 ,3 0 11.1 Hz, J 3 0 ,4 0 3.6 Hz, H-3 0 ), 5.57 (d, 1H, J 2 0 ,3 0 11.1 Hz, H-2 0 ), 5.50 (dd, 1H, J 3 0 ,4 0 3.6 Hz, J 4 0 ,5 0 1.1 Hz, H-4 0 ), 380 4.85 (ddd, 1H, J 5 0 ,6 0 a 6.8 Hz, J 5 0 6 0 b 6.3 Hz, J 4 0 ,5 0 1.1 Hz, H-5 0 ), 4.15 (dd, 1H, J 6 0 a,6 0 b 11.6 Hz, J 5 0 ,6 0 a 6.8 Hz, H-6 0 a) 4.09 (dd, 1H, J 6 0 a,6 0 b 11.6 Hz, J 5 0 ,6 0 b 6.3 Hz, H-6 0 b), 2.16, 2.05, 2.03, 1.97 (4s, 12H, OCOCH 3 ), 1.92–1.84 (m, 4H, 2CH 2 ), 1.82–1.68 (m, 4H, 2CH 2 ); 13 C NMR (CDCl 3 , 90 MHz): d(ppm): 170.0 (2), 169.6, 169.0 (CO), 158.8 (C-4, 3 J H-2 0 ,C-4 =6.1 Hz), 116.2 (C-2), 100.1 (C-1 0 ), 69.9, 68.6, 67.3, 67.2 (C-2 0 –C-5 0 ), 61.2 (C-6 0 ), 38.2, 36.6, 23.6, 22.6 (4CH 2 ), 20.6, 20.5 (2), 20.4 (COCH 3 ); Calcd for C 20 H 27 NO 11 (Mol. Wt.: 457.43, Ex. Mass.: 457.16); ESI-MS (positive mode) m/z:480.149 [M+Na] + , 937.306 [2M+Na] + . 390 Fraction II: Traces of 3d insufficient for NMR characterization. Calcd for C 20 H 27 NO 11 (Mol. Wt.: 457.43, Ex. Mass.: 457.16); ESIMS (positive mode) m/z:480.147 [M+Na] + , 937.306 [2M+Na] + . Fraction III: 0.045 g (26%) of 4 14 as a white solid. 3.2.4. (1 0 R)- and (1 0 S)-2 0 ,3 0 ,4 0 ,6 0 -tetra-O-acetyl-1 0 ,5 0 -anhydroD - galactitol-spiro-[1 0 ,5]-4-imino-1,3-dioxolane-spiro-[2,1]- cyclohexanes (2e and 3e) Prepared from 1(0.50 g, 1.10 mmol) and cyclohexane with AgOTf according to General procedure I (Section 3.2). Column chromatography (1:1 EtOAc–hexane) gave three fractions. 400 Fraction I: 0.23 g (44%) of 2e as white crystals; mp: 124–126 °C; [ a ] D +14 (c0.22, CHCl 3 ); 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 7.40 (s, 1H, NH), 6.01 (dd, 1H, J 2 0 ,3 0 10.5 Hz, J 3 0 ,4 0 3.2 Hz, H-3 0 ), 5.57 (d, 1H, J 2 0 ,3 0 10.5 Hz, H-2 0 ), 5.51 (dd, 1H, J 3 0 ,4 0 3.2 Hz, J 4 0 ,5 0 1.0 Hz, H-4 0 ), 4.85 (ddd, 1H, J 5 0 ,6 0 a 7.3 Hz, J 5 0 ,6 0 b 6.3 Hz, J 4 0 ,5 0 1.0 Hz, H-5 0 ), 4.10–4.08 (m, 2H, H-6 0 a, H-6 0 b), 2.18, 2.08, 2.04, 1.97 (4s, 12H, OCOCH 3 ), 1.87–1.81 (m, 2H, CH 2 ), 1.77–1.56 (m, 4H, 2CH 2 ), 1.53–1.33 (m, 2H, CH 2 ), 1.30–1.23 (m, 2H, CH 2 ); 13 C NMR (CDCl 3 , 90 MHz): d(ppm) 170.8 (2), 169.2, 169.8 (CO), 158.2 (C-4, 3 J H-2 0 ,C4 =5.3 Hz), 113.2 (C-2), 100.1 (C-1 0 ), 69.9, 68.9, 67.5 (2) (C-2 0 –C410 5 0 ), 61.3 (C-6 0 ), 37.2, 36.4, 24.4, 23.1 (2) (5CH 2 ), 20.8, 20.6 (2), 20.3 (COCH 3 ); Calcd for C 21 H 29 NO 11 (Mol. Wt.: 471.46, Ex. Mass.: 471.17); ESI-MS (positive mode) m/z:494.164 [M+Na] + , 965.339 [2M+Na] + . Fraction II: 0.04 g (8%) of 3e as white crystals; mp: 112–114 °C; [ a ] D +23 (c0.20, CHCl 3 ); 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 7.40 (s, 1H, NH), 5.75 (d, 1H, J 2 0 ,3 0 10.5 Hz, H-2 0 ), 5.50 (dd, 1H, J 3 0 ,4 0 3.2 Hz, J 4 0 ,5 0 1.0 Hz, H-4 0 ), 5.26 (dd, 1H, J 2 0 ,3 0 10.5 Hz, J 3 0 ,4 0 3.2 Hz, H-3 0 ), 4.41 (ddd, 1H, J 5 0 ,6 0 a 7.3 Hz, J 5 0 ,6 0 b 6.3 Hz, J 4 0 ,5 0 1.0 Hz, H-5 0 ), 4.16 (dd, 1H, J 6 0 a,6 0 b 11.6 Hz, J 5 0 ,6 0 a 7.3 Hz, H-6 0 a), 4.07 (dd, 1H, J 6 0 a,6 0 b 420 11.6 Hz, J 5 0 ,6 0 b 6.3 Hz, H-6 0 b), 2.20, 2.06, 2.01, 1.95 (4s, 12H, OCOCH 3 ), 1.88–1.81 (m, 2H, CH 2 ), 1.79–1.60 (m, 6H, 3CH 2 ), 1.52–1.41 (m, 2H, CH 2 ); 13 C NMR (CDCl 3 , 90 MHz): d(ppm) 170.3 (2), 168.9, 168.8 (CO), 160.3 (C-4), 113.1 (C-2), 100.8 (C-1 0 ), 69.7, 69.3, 67.7, 66.0 (C-2 0 –C-5 0 ), 61.8 (C-6 0 ), 37.0, 36.0, 24.3, 23.3 (2) (5CH 2 ), 20.6 (2), 20.5 (2) (COCH 3 ); Calcd for C 21 H 29 NO 11 (Mol. Wt.: 471.46, Ex. Mass.: 471.17); ESI-MS (positive mode) m/z: 494.164 [M+Na] + , 965.336 [2M+Na] + . Fraction III: 0.11 g (25%) of 4 14 as a white solid. 3.2.5. (1 0 R)-2 0 ,3 0 ,4 0 ,6 0 -Tetra-O-benzoyl-1 0 ,5 0 -anhydroD -glucitol430 spiro-[1 0 ,5]-2,2-dimethyl-4-imino-1,3-dioxolane (6a) Prepared from 5(0.50 g, 0.71 mmol) and acetone with AgOTf according to General procedure I (Section 3.2). Column chromatography (1:2 EtOAc–hexane than EtOAc) gave two fractions. Fraction I: 0.18 g (37%) of 6a as a colourless oil; R f = 0.51 (1:2 EtOAc–hexane); [ a ] D +63 (c0.52, CHCl 3 ); 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 8.04–7.24 (m, 20H, ArH), 7.73 (s, 1H, NH), 6.80 (pseudo t, 1H, J 2 0 ,3 0 10.2 Hz, J 3 0 ,4 0 9.7 Hz, H-3 0 ), 5.85 (d, 1H, J 2 0 ,3 0 10.2 Hz, H-2 0 ), 5.76 (pseudo t, 1H, J 4 0 ,5 0 9.9 Hz, J 3 0 ,4 0 9.7 Hz, H-4 0 ), 5.13 (ddd, 1H, J 4 0 ,5 0 9.9 Hz, J 5 0 ,6 0 b 4.5 Hz, J 5 0 ,6 0 a 1.2 Hz, H-5 0 ), 440 4.63 (dd, 1H, J 6 0 a,6 0 b 12.0 Hz, J 5 0 ,6 0 a 1.2 Hz, H-6 0 a), 4.47 (dd, 1H, J 6 0 a,6 0 b 12.0 Hz, J 5 0 ,6 0 b 4.5 Hz, H-6 0 b), 1.61, 1.29 (2s, 6H, CH 3 ); 13 CNMR (CDCl 3 , 90 MHz): d(ppm) 166.0, 165.4, 165.3, 164.8 (CO), 160.5 (C-4, 3 J H-2 0 ,C-4 =5.4 Hz, from HSQMBC at 125 MHz), 112.8 (C-2), 100.3 (C-1 0 ), 70.8, 70.7, 70.5, 69.4 (C-2 0 –C-5 0 ), 63.1 (C-6 0 ), 27.6, 26.7 (CH 3 ); Calcd for C 38 H 33 NO 11 (Mol. Wt.: 679.67, Ex. Mass.: 679.21); ESI-MS (positive mode) m/z:702.190 [M+Na] + , 1381.399 [2M+Na] + . Fraction II: 0.21 g (46%) of 7 32 as a white solid. 3.2.6. (1 0 R)-2 0 ,3 0 ,4 0 ,6 0 -Tetra-O-benzoyl-1 0 ,5 0 -anhydroD -glucitol450 spiro-[1 0 ,5]-2,2-diethyl-4-imino-1,3-dioxolane (6c) Prepared from 5(0.50 g, 0.71 mmol) and pentan-3-one with AgOTf according to General procedure I (Section 3.2). Column chromatography (1:2 EtOAc–hexane than EtOAc) gave two fractions. Fraction I: 0.23 g (46%) of 6c as a white foam; R f = 0.49 (1:2 EtOAc–hexane); [ a ] D +60 (c0.40, CHCl 3 ); 1 H NMR (CDCl 3 , 360 MHz): d(ppm) 8.05–7.20 (m, 20H, ArH), 7.71 (s, 1H, NH), 6.82 (pseudo t, 1H, J 2 0 ,3 0 10.2 Hz, J 3 0 ,4 0 9.8 Hz, H-3 0 ), 5.92 (d, 1H, J 2 0 ,3 0 10.2 Hz, H-2 0 ), 5.76 (pseudo t, 1H, J 3 0 ,4 0 9.8 Hz, J 4 0 ,5 0 9.7 Hz, H-4 0 ), 5.13 (ddd, 1H, J 4 0 ,5 0 9.7 Hz, J 5 0 ,6 0 b 5.6 Hz, J 5 0 ,6 0 a 2.2 Hz, H-5 0 ), 460 4.64 (dd, 1H, J 6 0 a,6 0 b 12.0 Hz, J 5 0 ,6 0 a 2.2 Hz, H-6 0 a), 4.50 (dd, 1H, J 6 0 a,6 0 b 12.0 Hz, J 5 0 ,6 0 b 5.6 Hz, H-6 0 b), 1.87 (q, 2H, J7.2 Hz, CH 2 CH 3 ), 1.57 (q, 2H, J7.4 Hz, CH 2 CH 3 ), 0.90 (t, 3H, J7.4 Hz, CH 2 CH 3 ), 0.63 (t, 3H, J 7.4 Hz, CH 2 CH 3 ); 13 C NMR (CDCl 3 , 90 MHz): d(ppm) 165.9, 165.4 (2), 164.8 (CO), 160.6 (C-4, 3 J H-2 0 ,C-4 =4.9 Hz), 116.6 (C-2), 99.9 (C-1 0 ), 70.9, 70.7, 70.5, 69.5 (C-2 0 –C-5 0 ), 63.0 (C-6 0 ), 31.2, 29.1 (CH 2CH 3 ), 7.8, 6.6 (CH 2 CH 3 ); Calcd for C 40 H 37 NO 11 (Mol. Wt.: 707.72, Ex. Mass.: 707.24); ESI-MS (positive mode) m/z:730.223 [M+Na] + , 1437.468 [2M+Na] + . Fraction II: 0.16 g (35%) of 7 32 as a white solid. 470 3.2.7. (1 0 R)-2 0 ,3 0 ,4 0 ,6 0 -Tetra-O-benzoyl-1 0 ,5 0 -anhydroD -glucitolspiro-[1 0 ,5]-4-imino-1,3-dioxolane-spiro-[2,1 00 ]-cyclopentane (6d) Prepared from 5(0.50 g, 0.71 mmol) and cyclopentanone with Ag 2 CO 3 according to General procedure I (Section 3.2). Column A. Páhi et al. / Carbohydrate Research xxx (2014) xxx–xxx 7 CAR 6720 No. of Pages 11, Model 5G 15 April 2014 Please cite this article in press as: Páhi, A.; et al. Carbohydr. Res. (2014), http://dx.doi.org/10.1016/j.carres.2014.04.003