Peter M. Collins

Specific Chemical Dissociation of Fibrillar and Non-Fibrillar Components of Amyloid Deposits

In systemic amyloidosis, a fatal disorder for which there is no effective treatment, the extracellular protein deposits are composed of amyloid fibrils together with a non-fibrillar glycoprotein, amyloid P component (AP). Methyl 4,6-O-(1-carboxyethylidene)-beta-D-galactopyranoside (MO beta DG), a recently identified ligand for AP, was tested for its ability to produce in-vitro elution of AP which had been laid down with amyloid fibrils in vivo. Millimolar concentrations of MO beta DG completely dissociated AP from human and murine splenic amyloid deposits. Availability of this material thus provides for the first time the opportunity for specific molecular dissection of amyloid deposits. If MO beta DG or a related substance were effective in vivo it might be of therapeutic importance.

A study of ruthenium tetroxide as an oxidant for alcohols

Abstract The oxidation of benzhydrol and partially protected sugars with ruthenium tetroxide has been studied and the stoichiometry of the reaction verified. Axial and equatorial hydroxyl groups on an otherwise protected pyranoid ring are oxidized with equal ease. The generation of the tetroxide with periodate and ruthenium dioxide has been confirmed to be an easy reaction, providing that the dioxide has been prepared by the precipitation process.

Intramolecular 1,3-dipolar additions in 4-O-allyl pyranoside 6-nitrones: An approach to chiral pyrano-pyrans and pyrano-oxepans

Abstract Treatment of the easily prepared 6-aldehydo-glucopyranoside allyl ether (5) with N-benzylhydroxylarnine gave nitrone (6), which underwent a 1,3-dipolar addition to the 4-O-allyl group giving after deprotection and hydrogenolysis the chiral pyrano-pyran (11) and the pyrano-oxepan (13).

Titanium-mediated methylene transfer reactions on sugar esters, lactones, and uloses

The titanium alkylidene 1, a versatile methylenating agent readily derived’ from the rather costly Tebbe compound 2, has been used in Wittig-type reactions to convert ketones into olefins and esters into vinyl ethers’. We now reportt its application to a variety of sugar derivatives that contain carbonyl and/or ester functions, with the aim of delineating the scope of the reaction with respect to blocking groups and the structure of the ketone, ester, or lactone. In order to simplify the procedure and increase the value of the method, the unpurified form of 2 was used (see Experimental). Pure, crystalline Tebbe reagent has been used by others3t4 on some aldonolactones and, where comparisons can be made, both similarities and differences were found. Reaction of the ulose 3 (X = 0) and the aldehyde 5 (R = H) with 2 gave, after chromatography, 70% and 35%, respectively, of the olefins 4’*(’ and 6 (R = H)7 in experiments that were easier to execute than the customary Wittig procedure5. Mono-esters of sugars were converted smoothly into vinyl ethers. Thus, 1,2:5,6di-0-isopropylidene-u-D-glucofuranose 3-acetate, 3-benzoate, and 3-p-chlorobenzoate gave, in good yields, the respective substituted vinyl ethers 7 (R = Me, or Ph, or ClC6H4). Each of the vinyl ethers 7 was susceptible to hydrolysis and gave methyl ketones uiu hemiacetals. The stability of these compounds towards hydrolysis increased in the order cited. Esters of glycuronic acids reacted readily with the crude 2, thereby affording a route to chain-extended sugars. The methyl glucoronate derivative 8 gave the methylene compound 9, and the methyl galacturonate derivative 5 (R = OMe) gave compound 6 (R = OMe), which needed more careful handling than 9 because it was rapidly hydrolysed on silica gel with neutral eluants to give the useful ketone 5 (R = Me). The &lactones 2,3,4,6-tetra-O-methyl-p-glucono-1,5-lactone (10, R = Me) and

The synthesis and solvolysis of some fully acetylated glycopyranosylulose chlorides

Abstract Several partially acetylated aldopyranosyl chlorides with an unprotected hydroxyl group at C-2 have been synthesised and some have been oxidised with ruthenium tetraoxide. In this way, fully acetylated pyranosylulose chlorides having the α- D - arabino -hexo, α- D - lyxo -hexo, and β- L - erythro -pento structures have been prepared. Their rates of methanolysis have been determined. Key intermediates in the synthetic sequences were the per- O -acetyl-2- O -trichloroacetylglycopyranosyl chlorides, of which the α- and β- D - galacto , α- and β- L - arabino , and α and β- D - xylo compounds were hitherto unknown. The β- D - xylo derivative exists in the conformation in which all the ring substituents are axially disposed, whereas the α- L - arabino compound is a rare example of an acylated pentopyranosyl chloride that adopts, preponderantly, a chair conformation that places the halogen in an equatorial orientation.

A new cycloglucohexaose derivative the chemical synthesis of Cyclo{→3-[β-D-Glcp-(1→3)-]5-D-Glcp(1→)}

Abstract The new 1→3 β-linked cycloglucohexaose derivatives (1) and (2) have been prepared from 1,2-O benzylidene-4,6-O-ethylidene-a-D-glucopyranose and its derivatives as the monomeric building blocks, using as a key reaction their photobrominative conversion into 2-O-benzoyl-glucosyl bromides.

The synthesis of some o-nitrobenzylidene derivatives of aldopyranosides

Abstract The preparation of the following new compounds is reported: the 4,6, O - o -nitrobenzylidene derivatives of methyl α- and α- D -glucopyranoside and - D -galactopyranoside, methyl α- D -mannopyranoside, and the corresponding 2,3-diacetates; the 2,3- O - o -nitrobenzylidene derivatives of methyl 4,6-di- O -methyl-β- D -allopyranoside, methyl α- L -rhamnopyranoside and its 4-acetate ( 11 ), the 3,4- O - o -nitrobenzylidene derivatives of 1,6-anhydro-2- O -methanesulphonyl- D -galactopyranose, methyl β- L - arabinopyranoside, methyl α- L -fucopyranoside, and the 2- O -acetyl derivatives ( 13 and 15 ) of the last two compounds, and 2,3:4,6-di- O - o -nitrobenzylidene-α- D -mannopyranoside ( 19 ). The n.m.r. spectra of the endo and exo forms of four of the dioxolane derivatives, 11 , 13 , 19 , and 15 , are presented. The first three of these compounds have been fractionated into pure endo and exo forms.

Further studies of ruthenium tetroxide as an oxidant for carbohydrate derivatives

Abstract An extension is reported of the evaluation of ruthenium tetroxide as an oxidant for the conversion of partially protected carbohydrates into glycosulose derivatives. It has been demonstrated that free hydroxyl groups in benzoic and toluene- p -sulphonic esters, and in N -acetamido derivatives of glycosides can all be oxidised successfully by the reagent. It has been shown also that the oxidant converts 1,4:3,6-dianhydrohexitols into the corresponding 2,5-dione; no significant selectivity in the oxidation of endo and exo hydroxyl groups was noted. Comment is made on the abnormally high optical rotation of the bis(2,4-dinitrophenylhydrazone) of 1,4:3,6-dianhydro- d - threo -hexo-2,5-diulose.

4,6-O-benzylidene-1,2-dideoxy-d-erythro-hex-1-enopyran-3-ulose

Abstract 4,6-O-Benzylidene-1,2-dideoxy- d -exythro-hex-1-enopyran-3-ulose has been prepared in good yield from 4,6-O-benzylidene-1,2-dideoxy- d -ribo-hex-1-enopyranose. Chromium trioxide in pyridine is the most satisfactory oxidant. The n.m.r. spectra of this and other unsaturated pyranoid derivatives suggest that the magnitude of the cis vicinal vinylic coupling constant is reduced when the double bond in between C-1 and C-2. This is attributed to the electronic properties of the ring oxygen atom.

An efficient synthesis of sugar pyruvic acid acetals

Abstract 4,6-O-(Carboxyethylidene)-glycopyranosides (e.g. 10) may be prepared by oxidation of the corresponding furan-2-ylethylidene derivatives (e.g. 7) which in turn are readily produced by acetal exchange between the 4,6-hydroxy groups of glycopyranosides.