Roger W. Binkley

Synthesis and Reactions of Carbohydrate Trifluoro-Methanesulfonates (Carbohydrate Triplates)

Abstract During the past decade a new leaving group, the trifluoromethanesufonate (triflate), has been used increasingly in displacement reactions in carbohydrate chemistry∗. The importance of this group has become progressively more apparent to the synthetic carbohydrate chemist as the examples of triflate displacement have increased. The number of applications of this reaction now has reached a sufficient magnitude that it seems appropriate to review what has been accomplished.

Photochemical Reactions of Carbohydrates

Publisher Summary This chapter describes the various aspects of the photochemical reactions of carbohydrates. The most important photochemical reaction of carbon to carbon unsaturated carbohydrates is the addition to the unsaturated system. Two types of addition reaction are readily recognized. First consists of those in which the molecule adding to the carbohydrate is done by involving a π-bond of its own. The second class of addition reaction is one in which a σ-bond is broken in the molecule adding to the unsaturated carbohydrate. Cycloaddition reactions involving unsaturated carbohydrates are regio- and stereo-selective. For addition reactions other than cycloaddition, unsaturated carbohydrates follow one of the two fundamental pathways. The more common of the two begins with radical formation arising from bond homolysis in the noncarbohydrate reactant. A group of acid-catalyzed addition-reactions has been observed for which the catalyst appears to arise from photochemical decomposition of a noncarbohydrate reactant. Photochemical, carbon–sulfur bond cleavage is also observed in the compounds containing sulfur in oxidation states higher than that exists in sulfides and in dialkyl dithioacetals. Photolysis of azides is considered to generate a nitrene, whereas photolysis of oximes produces an iminolactone that may arise by way of nitrogen–oxygen-bond homolysis followed by hydrogen-atom transfer. It is found that the yield of the next-lower aldose from an oxime irradiation is quite dependent upon the particular oxime photolyzed.

Photoremovable Protecting Groups

Selective reaction in molecules which contain more than a single functional group is an essential element in nearly all organic synthesis. Achieving this selectivity can be a challenging problem in reactions of compounds which contain a number of functional groups, particularly if those functional groups are all of the same type (e.g., carbohydrates). Perhaps the most common method for obtaining selective reaction is through the use of protecting groups. One indication of the importance of these groups is the continuing rise in the number of new protecting groups described each year. At present this number appears to be doubling every decade.(1)

Reactions of Per-O-Acetylated Carbohydrate Triflates With Halide Ions

Abstract The reactions of bromide, chloride, and iodide ions with 1,3,4, 6-tetra-O-acetyl-2-O-(trifluoromethylsulfonyl) -α-D-glucopyranose (2) and with 1, 3, 4, 6-tetra-O-acetyl-2-O-(trifluoromethylsulfonyl)-β-D-mannopyranose (3) gave good to excellent yields of the corresponding deoxyhalogeno sugars. In contrast, when the gluco triflate 2 and tetra-butylammonium fluoride were heated under reflux in benzene, only 5-(acetoxymethyl)-2-formylfuran (13) was formed. Reaction of the manno triflate 3 under similar conditions produced 1, 3,4, 6-tetra-O-acetyl-2-deoxy-2-fluoro-β-D-gluco-pyranose (17), 1. 3, 4. 6-tetra-O-acetyl-2-deoxy-β-D-erythro-hex-2-eno-pyranose (18), 4,6-di-O-acetyl-1, 5-anhydro-2-deoxy-D-erythro-hex-l-enitol-3-ulose (19), and 1, 2, 3, 4, 6-penta-O-acetyl-β-D-glucopyranose (20). The mechanisms of the reactions of The triflates 2 and 3 with fluoride ion are discussed.

Photochemically Based Synthesis of Deoxy Sugars. Synthesis of 2-Deoxy-D-Arabino-Hexopyranose (2-Deoxy-D-Glucose) and Several of Its Derivatives from 3,4,6-Tri-O-Acetyl-D-Glucal

Abstract The photolysis of methyl 3,4,6-tri-O-acetyl-2-bromo-2-deoxy-β-D-glucopyranoside (2) in 2-propanol results in replacement of the bromine with a hydrogen to give methyl 3,4,6-tri-O-acetyl-2-deoxy-β-D-arabino-hexopyranoside (4) in 91% yield. Similar reactions take place for methyl 3,4,6-tri-O-acetyl-2-bromo-2-deoxy-α-D-mannopyranoside (3) and a mixture of the a and β anomers of 1,3,4,6-tetra-O-acetyl-2-bromo-2-deoxy-D-glucopyranose (7) and 1,3,4,6-tetra-O-acetyl-2-bromo-2-deoxy-D-mannopyranose (8). Since compounds 2, 3, 7, and 8 each were synthesized from 3,4,6-tri-O-acetyl-D-glucal (1), photochemical reaction appears to be a useful process in 2-deoxy sugar synthesis from glycals.

Photochemical reactions of carbohydrates : II. The photochemistry of 6-deoxy-6-iodo-1,2:3,4-di-O-isopropylidene-α-d-galactopyranose

Abstract Ultraviolet irradiation (Pyrex filter) of a methanol solution of 6-deoxy-6-iodo-1,2:3,4-di- O -isopropylidene-α- d -galactopyranose ( 1 ) in the presence of sodium hydroxide led to rapid, almost quantitative conversion of 1 into 6-deoxy-1,2:3,4-di- O -isopropylidene-α- d -galactopyranose ( d ). The yield of 2 was found to depend on the solvent and on the energy of the light used for irradiation. The direct irradiation of 1 in tert -butyl alcohol in the presence of sodium hydroxide gave 2 in only 36% yield, together with 6-deoxy-1,2:3,4-di- O -isopropylidene- l - arabino -hex-eno-pyranose ( 4 ) in 32% yield. A mechanism is proposed in which the initial step is the light-induced homolysis of the carbon-iodine bond in 1 to a radical species ( 5 ) and an iodine atom. The products formed from 5 depend on the relative ease of abstraction of hydrogen from the solvent.

Synthesis of Methyl 2,6-Dideoxy-3-C-Methyl-α-D-ribo- hexopyranoside (Methyl α-D-Mycaroside), a Component of the Antitomor Agent Mithramycin

Abstract Methyl α-D-mannopyranoside (4) was converted into methyl 2,6-dideoxy-3-C-methyl-ct-D-ribo-hexopyranoside (20) (methyl α-D-mycaroside) by an efficient sequence of reactions (Schemes 1 and 3). A similar set of reactions also was used to convert L-rhamnose (2) into methyl α-L-mycaroside (21). Attempted synthesis of methyl 2,6-diseoxy-3-C-methyl-a-D-arabino-hexopyranoside (22) (methyl α-D-olivomycosidej from methyl 6-deoxy-3-C-methyl-4-O-(2,2-dimethylpropanoyl)∼2-O-trif lyl-α-D-arabino-hexopyranoside (18), a compound generated during∼synthesis of 20, was thwarted by a methyl migration which produced methyl 2,6-dideoxy-2-C-methyl-α-D-ribo-hexopyranoside (23).

A Photochemical Sequence for Oxidation of Alcohols to Carbonyl Compounds

Abstract In the early nineteen sixties the photochemical reactions of three esters of pyruvic acid were reported1,2 (equation 1). The products from these reactions suggested that pyruvate formation followed by photochemical reaction could be a new technique for oxidation of alcohols to carbonyl compounds. At the time, the forcing conditions necessary for esterification of pyruvic acid3 would have discouraged further consideration of pyruvate photolysis as a part of a mild oxidation process. The recent report of a facile synthesis of the acid chloride of pyruvic acid4 raised the possibility that the esterification-photoreaction sequence for oxidation could become a useful synthetic tool. This new reaction sequence now has been investigated for a series of alcohols and found to be a promising oxidation pathway.

β-Disaccharides for Mithramycin Analog Synthesis. Triflate Rearrangement in Disaccharide Preparation.

ABSTRACT Three disaccharides (13, 16, and 20), compounds to be utilized in the preparation of analogs of the anticancer agent mithramycin (1), have been synthesized from appropriately protected 2,6-dideoxy sugars. In these syntheses triflate rearrangement was used to invert configuration at specific chiral centers. Silver-silicate controlled reaction generated the desired β-linkages between saccharide units. Silver-silicate also catalyzed β-glycoside formation when the glycosyl bromides derived from 13 and 20 each were coupled with o-methylphenol (a model aglycon).

Aglycon-Disaccharide Coupling in Mithramycin Analog Synthesis

ABSTRACT Mithramycin (1), chromomycin A3, and olivomycin A are structurally related, antitumor agents which belong to the aureolic acid family of antibiotics.1 Considerable research on the synthesis of both the aglycon2-4 and carbohydrate7-9 portions of these molecules naturally has led to interest in methods for joining carbohydrate and aglycon units together.10 One type of coupling which is required for aureolic acid synthesis is that of the A-B disaccharide to the phenolic hydroxyl group at C-6.11 In this communication such a process is described along with a flexible procedure for the formation of the protected A-B disaccharide used in the coupling process.