Donald E. Kiely

A synthesis of (±)myo-inositol 1-phosphate

Abstract An uncomplicated synthesis of (±)- myo -inositol 1-phosphate ( 7 ) is described. Phosphorylation of (±)-3,4,5,6-tetra- O -benzyl- myo -inositol ( 2 ) with phosphorus oxychloride gave the corresponding 1- and 2- phosphates, isolated as a mixture of their bis(cyclohexylamine) salts. Fractional crystallization of the regenerated free phosphates gave (±)-3,4,5,6-tetra- O -benzyl- myo -inositol 1-phosphate ( 5 ), which afforded (±)- myo -inositol 1-phosphate ( 7 ) after removal of the benzyl groups by catalytic hydrogenolysis.

Oxidation of carbohydrates with chromic acid The synthesis of the delta-dicarbonyl monosaccharides 6-deoxy-D-xylo-hexos-5-ulose and 6,7-dideoxy-d-xylo-heptos-5-ulose☆☆☆

Abstract Addition of the alkyl Grignard reagents methylmagnesium iodide and ethylmagnesium bromide to the aldehyde 3-O-benzyl-1,2-O-isopropylidene-α- d -xylo-pentodialdo-1,4-furanose (1) gave a preponderance of the corresponding 6-deoxy- and 6,7-dideoxy- l -ido derivatives (2 and 3). Oxidation of these alcohols with chromic acid gave the 5-keto derivatives 6 and 7 in high yield. The benzyl group of 6 was cleaved by catalytic hydrogenolysis, and acid-catalyzed hydrolysis of the isopropylidene group afforded the delta-dicarbonyl monosaccharide 6-deoxy- d -xylo-hexos-5-ulose (10). The same sequence applied to 7 gave 6,7-dideoxy- d -xylo-heptos-5-ulose (11). An alternative route to 8 consisted in reversing the order of the oxidation and hydrogenolysis steps, starting with 2 or its d -gluco isomer 4. In this sequence, chromic acid was used for selectively oxidizing the 5- (rather than the 3-) hydroxyl group of the l -idofuranose and d -glucofuranose derivatives 12 and 13.

5-Keto-Mannose (D-Lyxo-Hexos-5-Ulose) in Aqueous Solution-Isomeric Composition Dominated by α/β D-Fructofuranose Related Structures

Abstract Selective C-6 hydroxyl triphenylmethylation of methyl 2,3-O-isopropylidene-α-D-mannofuranose (1), followed by C-5 hydroxyl oxidation and sequential removal of protecting groups in aqueous acid, yielded D-lyxo-hexos-5-ulose (5-keto-mannose, 5) as a mixture of isomeric forms. The isomeric mixture of 5 in D2O solution was carefully examined using 1H and 13C NMR techniques and structural assignments were made for seven isomers. The most prevalent form of 5 observed was the ketofuranose isomer 2S, 5R-D-lyxo-hexo-5,2-furanos-5-ulose 1-hydrate (5a, 52%), with its 2S, 5S-ketofuranose anomer (5b) being the next most abundant (14%). Also identified in the mixture were the α and β-hexofuranos-5-uloses 5c (6%) and 5d (< 2%), the pyranose structure 1R,5R-lyxo-hexopyranos-5-ulose 5e (10%), and the anhydro isomer 1R,5R-1,6-anhydro-D-lyxo-hexopyranos-5-ulose (5f, 5%), present in 1 C 4 conformation. Limited spectral information suggests that the remaining isomer 5g (8%) is a hydrated acyclic aldehyde form of 5.

d-Glucaric Acid Esters/Lactones Used in Condensation Polymerization to Produce Hydroxylated Nylons—A Qualitative Equilibrium Study in Acidic and Basic Alcohol Solutions

Abstract Direct esterification of d-glucaric acid in acidic methanol solution produced a mixture of four esters/lactones: dimethyl d-glucarate (1), methyl d-glucarate 1,4-lactone (2), methyl d-glucarate 6,3-lactone (3), and d-glucaro-1,4:6,3-dilactone (4). The esters/lactones described in this study are activated forms of d-glucaric acid useful for condensation polymerization with diamines to produce hydroxyated nylons. Structures of the esterification products were determined using 1H NMR, 13C NMR and GC/MS techniques. Qualitative changes in equilibrium concentrations of the esters/lactones mixtures, as determined from 1H NMR spectral studies, were observed in acidic (methanol-d4/HCl) and basic (methanol-d4/triethylamine) alcohol solutions. Esterification of d-glucaric acid in ethanol produced ethyl esters/lactones mixtures which were observed to undergo changes in equilibrium composition in acidic and basic ethanol solutions comparable to those found with the methyl esters/lactones mixtures.

The Isomeric Composition of D-ribo-hexos-3-ulose(3-keto-D-glucose) in Aqueous Solution1

Abstract 1,2:5,6-Di-O-isopropylidene-α-D-ribo-hexofuranos-3-ulose (2) prepared by the phase transfer catalyst promoted ruthenium tetraoxide oxidation of 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (1), was partially hydrolyzed to give 1,2-O-isopropylidene-α-D-ribo-hexos-3-ulose (3). The title compound (4) was prepared by further acid hydrolysis of 3 or directly from 2. The anomeric region of the 1H NMR spectrum of freshly prepared 4 showed the presence of at least ten isomeric forms with three forms predominating: α-D-ribo-hexofuranos-3-ulose (4a, 44%), β-D-ribo-hexopyranos-3-ulose (4b, 22%) and β-D-ribo-hexopyranos-3-ulose hydrate (4c, 12%). 1H NMR examination of D2O solutions of 4 over time showed that the C-2 protons of the various isomeric forms were being exchanged with deuterium.

The Isomeric Composition of 6-Deoxy-D-XYLO-Hexos-5-Ulose in Aqueous Solution as Determined by 1H and 13C NMR

Abstract Acid hydrolysis of 6-deoxy-1,2-O-isop ropylidene-α-d-xylo-hexo-furanos-5-ulose (4) yielded gummy 6-deoxy-d-xylo-hexos-5-ulose (1) as an isomeric mixture of two furanose forms, 6-deoxy-α-d-xylo-hexo-furanos-5-ulose and 6-deoxy-β-d-xylo-hexofuranos-5-ulose, and a pyranose structure 1R, 5R-6-deoxy-d-xylo-hexopyranos-5-ulose. The combined percentage (64%) of the furanoses represents an unusually large amount of free carbonyl form for a sugar when compared to simple hexoses and 2-hexuloses. Isomeric structures were determined in deuterium oxide solution by 1H and 13C NMR.

The Isomeric Composition of D-Xylo-hexos-5-ulose (5-Keto-glucose) in Aqueous Solution

Abstract 1,2-O-Isopropylidene-α-D-xylo-hexofuranos-5-ulose (2) was deprotected in aqueous acid solution to give a mixture of at least six isomeric forms and one anhydro form of the parent ketoaldohexose, D-xylo-hexos-5-ulose (3), commonly referred to as 5-keto-glucose. Structural assignment of each form was made based on high field 1H and 13C NMR studies of the mixture in aqueous (D2O) solution. The dominant isomeric form of 3 was observed to have the pyranose structure 1R,5R-D-xlyo-hexo-pyranos-5-ulose (3a, 67 %) with the next most abundant form being an anhydro structure, 1S,5S-l,6-anhydro-D-xylo-hexopyranos-5-ulose (3c, 18 %). Included among the other isomers were the a and β-1,4-furanose (3d, 3e) and 1-aldehydrol β-5,2-furanose (3f) structures. The isomer present in least amount (3g, > 1 %) is assigned as the α-anomer of 3f. Experimentally determined JC-1,H-1 values were useful in support of assigned isomer structures.

A General Synthesis of Diterminal Diamnodideoxyalditols and 1-Amino-1-deoxyalditols Using Trimethylmsilyl Protecting Groups

Abstract General syntheses of diterminal diaminodideoxyalditols and 1-amino-1-deoxyalditols from aldoses are described. Borane-THF reduction of O-trimethylsilylaldaramides, followed by methanolic HC1 workup, leads to diaminodideoxyalditol dihydrochlorides. Similar treatment of O-trimethylsilylaldonamides yields aminoalditol hydrochlorides. The general reaction sequence was used to synthesize six diaminoalditols and five monoaminoalditols. The method is generally applicable to both classes of title aminoalditols and is independent of the chain length and stereochemistry of the starting aldose.

Regiospecific Dehydration of Some Branched Cycloses and Cyclitols Derived From Activated 2,6-Heptodiulose Derivatives

Abstract The stereoselective base catalyzed conversion of tri-0-acetyl-l,7-dichloro-l,7-dideoxy-xylo-2,6-heptodiulose to d l-(2,3,4,6/5)-4,5,6-tri-0-acetyl-2-chloro-3-C-(chloromethyl)-3,4,5,6-tetrahydroxy-cyclohexanone has been described,1 and it has also been shown that branched cyclose formation from the corresponding 1,7-dibromo and 1,7-diazido-2,6-heptodiuloses also occurs in the same stereoselective manner.1 Reduction of the cyclose ketone function followed by appropriate deprotective leads to branched epi-inositols.1,2 The general structure of the starting 2,6-heptodiulose, and the product cyclose and cyclitol are given as I, II and III respectively.

Branched-chain halo- and animo-cyclitols: synthesis and an x-ray crystallographic study ☆

Abstract The base-catalyzed cyclizations of tri- O -acetyl-1,7-dibromo-1,7-dideoxy- xylo -2,6-heptodiulose ( 2 ), tri- O -acetyl-1,7-dichloro-1,7-dideoxy- xylo -2,6-heptodiulose ( 3 ), and tri- O -acetyl-1,7-di- C -azido-1,7-dideoxy- xylo -2,6-heptodiulose ( 4 ), to dL -4,5,6-tri- O -acetyl-2- C -bromo-3-C-(bromomethyl)- 2 , 3 , 4 , 6 / 5 -tetrahydroxycyclohexanone ( 5 ), dL -4,5,6-tri- O -acetyl-2-chloro-3- C -(chloromethyl)- 2 , 3 , 4 , 6 / 5 -tetrahydroxycyclohexanone ( 6 ), and dL -4,5,6-tri- O -acetyl-2- C -azido-3- C -(azidomethyl)- 2 , 3 , 4 , 6 / 5 -tetrahydroxycyclohexanone ( 7 ), respectively, are described. Reduction of the acetylated cycloses 5–7 by sodium borohydride proceeded with considerable stereoselectivity in producing branched epi -inositols, isolated as the tetraacetates 12 , 13 , and 18 . These latter compounds were used to prepare the corresponding unprotected cyclitols 24 , 25 , and 31 , and the branched amino- epi -inositols 27 , 29 , 30 , and 32 . The stereochemistry of the branched-chain cyclitols described appears to be the same as that of dL -1,4,5,6-tetra- O -acetyl-3-chloro-2- C -(chloromethyl)- epi -inositol ( 13 ), whose structure was confirmed by an X-ray crystallographic study.