D-Altropyranoside derivatives

H- and F N.m.r, Data for 3-Amino-2,3-dideoxy-2-fluoro-a-D-altropyranoside Derivatives (and Their N-Containing, Synthetic Precursors)... 

B. Coxon and R. C. Reynolds, Boat conformations. Synthesis, NMR spectroscopy, and molecular dynamics of methyl 4,6-0-benzylidene-3-deoxy-3-phthalimido-a-D-altropyranoside derivatives, Carbohydr. Res., 331 (2001) 461 67. 

Methyl 4,6-0-benzylidene-3-deoxy-3-phthalimido-a-D-altropyranoside derivatives 246... 

The phenanthridone alkaloid, lycoricidine 64 fScheme 12.32). is known to possess cytotoxic activity. Based on the retrosynthetic analysis as discussed in Section 12.3.2 f Scheme 12.18T the Chida group reported the total synthesis of lycoricidine starting from d-glucose in which the Ferrier carbocyclization reaction was enployed as the key reaction. For the preparation of the cyclohexene unit in lycoricidine, d-glucose was converted into 2-azido-d-altropyranoside derivative 122 via epoxide 121 fScheme 12.31T Protection of the diol moiety in 122 afforded 68, which was transformed into 5-enopyranoside 67 by the action of DBU. Ferrier carbocyclization of 67 with 1 mol% of Hg(OCOCF3)2, followed by p-elimination,... 

Several other methods for the introduction of halo atoms at C-6 in hexose derivatives have been known since the late 1920s. One of the earlier methods involved the reaction of methyl 2,3,4-tri-0-acetyl-6-0-trityl-a-D-glucopyranoside with phosphorus pentachloride which resulted only in an 8% overall yield of methyl 6-chloro-6-deoxy-a-D-glucoside (57). In contrast, the reaction of methyl 2,3,4-tri-0-acetyl-6-0-trityl-a-D-altropyranoside with phosphorus tribromide and bromine afforded a 73% yield of the corresponding 6-bromo-6-deoxy derivative (91). 

Methyl 4,6-O-benzylidene-a-D-altropyranoside showed little selectivity on reaction with a unimolar proportion of benzoyl chloride43 2-and 3-O-benzoyl and 2,3-di-O-benzoyl derivatives, together with starting material, were isolated in the molar ratios of 1 1.1 1.8 1. In contrast, benzoic anhydride in pyridine gave the 2-ester in 35% yield, with only a trace of the 3-benzoate. 

Many other glycosides have been subjected to selective chlorination with sulfuryl chloride. Methyl /3-L-arabinopyranoside afforded methyl 4-chloro-4-deoxy-a-D-xylopyranoside 2,3-di(chlorosulfate) in 29% yield, whereas the a-L anomer gave357 methyl 3,4-dichloro-3,4-dideoxy-/3-i)-ribopyranoside 2-(chlorosulfate) (30%). Methyl /3-d-ribopyranoside was converted into methyl 3,4-dichloro-3,4-dideoxy-a-L-arabinopyranoside through the action of pyridine hydrochloride on its 2,3,4-tri(chlorosulfate).358 Methyl a-D-lyxopyranoside gave only the 2,3,4-tri(chlorosulfate),353 as would be expected from the disposition of its hydroxyl groups, similar to that in the rhamno- and manno-pyranosides. Methyl a-D-altropyranoside was transformed into the 6-chloro-6-deoxy 2,3,4-tri(chlorosulfate) derivative in 80% yield.353... 

A novel method of opening of oxiranes involves the use of (chlo-romethylene)dimethyliminium chloride (39) [see Section II,2c p. 250], monochlorodeoxy or dichlorodideoxy derivatives are obtained, depending upon the reaction conditions employed.83 Thus, methyl 2,3-anhydro-4,6-0-benzylidene-a-D-allopyranoside (110) reacts with 39 in 1,1,2,2-tetrachloroethane at room temperature to give, upon hydrolysis of the primary adduct 111 with an aqueous solution of sodium hydrogen carbonate, methyl 4,6-0-benzylidene-2-chloro-2-deoxy-3-0-formyl-a-D-altropyranoside (112). If a solution of 39 and 110 in 1,1,2,2-tetrachloroethane is heated at reflux temperature, methyl 3,4-0-benzylidene-2,6-dichloro-2,6-dideoxy-o -D-altropyrano-side (113) is obtained in high yield the n.m.r. spectrum of 113, like that of 47 (see Section II, 2c p. 250), showed the presence of two diastereoisomers which differed in the configuration of the benzyl-idene-acetal carbon atom. 

Neighboring-group participation by the vicinal, trans-acetoxyl group (see p. 125) serves to explain the abnormal behavior of methyl 4-0-acetyl-2,3-anhydro-6-0-benzyl- or -trityl-a-D-gulopyranoside with hydrogen chloride in acetone, or with 80% aqueous acetic acid, which give D-galactose, instead of the D-idose, derivatives.67 In the same way, 2-0-acetyl-3,4-anhydro-D-altropyranosides yield D-man-nosides, not D-idosides.9 6z(see p. 125). 

The deamination of methyl 3-amino-3-deoxy-/3-D-altropyranoside was studied in 1934, but the products were not fully characterized.14411 The syrupy product was converted into a methylated derivative that had an elemental analysis corresponding to that calculated for a methyl tetramethylhexoside. The conditions used for methyl-ation would have opened an epoxide ring. Methyl 2,3-anhydro-4,6-0-benzylidene-a-D-mannopyranoside precipitated quantitatively from solution when the corresponding 3-amino-3-deoxyaltroside derivative was deaminated in aqueous medium.145 Epoxide formation was likewise reported to be quantitative in the deamination of the analogous 2-amino-2-deoxyaltroside.83 145 On deamination, 4-amino-l,6-anhydro-4-deoxy-/3-D-mannopyranose also gave an epoxide, namely, 1,6 2,3-dianhydro-/3-D-talopyranose, in unspecified yield.146... 

Methyl 4,6-O-benzyIidene-a-D-aItropyranoside. Triturate 4.0 g (0.015 mol) of the foregoing anhydro derivative in a mortar with a solution of 5 g of potassium hydroxide dissolved in 140 ml of water. Transfer the suspension to a round-bottomed flask and heat the mixture under reflux until all the solid has dissolved (about 28 hours). During this period solid material tends to creep up the inside of the flask surface shake periodically to re-suspend material. Remove the trace of insoluble matter which remains and neutralise the cooled filtrate with carbon dioxide (use phenophthalein as an indicator). Extract the solution with five 25 ml portions of dichloromethane, wash the combined extracts with a little cold water, dry over anhydrous sodium sulphate and remove the solvent under reduced pressure (rotary evaporator). Crystallise the syrup by scratching a small portion on a watch glass with ether stir the bulk syrup with ether and the seed crystals. Filter off and recrystallise the product from a small quantity of methanol to obtain 3.5 g (83%) of methyl 4,6-0-benzylidene-oc-D-altropyranoside, m.p. 174 °C, [a]D°+115° (c2 in CHCI3). 

Apparently the first definite assignment of a chair form to a six-membered, cyclic-acetal ring was made in order to explain the occurrence of only one stable isomer of methyl 4,6-0-benzylidene-,8-D-glucopyranoside, which will have the conformation L. The stable forms of 4,6-0-benzyli-dene derivatives of methyl /3-D-mannopyranoside, methyl 8-D-allopyrano-side, and methyl S-D-altropyranoside will differ from L only in the configurations at C2 and 03. "... 

Moffatt method for oxidation of both methyl 3-benzamido-4,6-0-benzylidene-3-desoxy-o-D-altropyranoside (6), of 2/J-hydroxy-3a-benzamido configuration, and the 2a-hydroxy-3/3-benzamido isomer (7), and in each case obtained the same 2-ketone in excellent yield. Oxidation of (6) to the 2-ketone promotes isomerization at the adjacent center to give the more stable equatorial 3/3-hydroxy derivative (4). 

A re-investigation of the reaction (conducted with methyllithium free from halide ion) which afforded the methylated derivative (1, R = Me, R = H), indicated that it proceeded by way of methyl 4,6-0-benzylidene-2-deoxy-2-C-methyl-a-D-altropyranoside (2, R= Me, R = H), because this compound [prepared by opening the corresponding 2,3-anhydroalloside with (methylsulfinyl)methyl carbanion, to give methyl 4,6-0-benzylidene-2-deoxy-2-C-[(methylsulfinyl) methyl]-a-D-altropyranoside (2, R = MeSOCH2, R = H), followed by reduction with Raney nickel], on treatment with methyllithium, also gave the C-methyl compound (1, R = Me, R = H).5... 

Methyl 4,6-0-benzylidene-a- and jS-n-altropyranosides have been prepared from the corresponding n-glucosides, which were first converted into the 2,3-di-p-toluenesulfonates. Subsequent treatment of the p-toluenesulfonate with sodium methoxide in the cold afforded the 2,3-anhydro derivative. The latter was then converted into the n-altroside by means of boiling potassium hydroxide, Methyl 4,6-0-benzylidene-a-D-altropyranoside is very resistant to oxidation by periodate ion and does not form a cuprammonium complex — in accordance with the expected CA conformation (34). 

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