Barbara Grzeszczyk

Homologation of Protected Hexoses with Grignard C1 Reagents

Abstract Derivatives of three stereoisomeric hexodialdo-1,5-pyranosides were reacted with four Grignard C1 reagents: methoxymethyl-, allyloxymethyl-, benzyloxymethyl, and dimethylphenylsilylmethyl-magnesium chlorides. Two stereoisomeric heptoses were obtained in each case in a good yield. The methyl alloside-derived heptosides were accompanied by C-5 inverted products. The addition of Grignard reagents to aldehydes 5–8 has been discussed in terms of parallel α- or β-chelated and Felkin–Anh transition states. It has been found that the silyl Grignard reagent 12 exhibits a strong preference for the formation of heptose derivatives of l -configuration at C-6.

Configuration of heptopyranoside and heptofuranoside side chains: 2‐anthroate, a powerful chromophore for exciton coupled CD

The absolute configuration of the acyclic side chain of heptopyranosides and heptofuranosides was determined by exciton coupled CD, employing the strongly fluorescent 2-anthroate chromophore. The usage of this chromophore offers significant improvements over previous chemical and spectroscopic procedures since its intense fluorescence greatly facilitates the isolation and HPLC purification at the nanogram scale. The large amplitudes of the bisignate spectra allow CD manipulations in the 1 x 10(-7) M range.

Synthesis of linear oligosaccharides: l-glycero-α-d-manno-heptopyranosyl derivatives of allyl α-glycosides of d-glucose, kojibiose, and 3-O-α-kojibiosyl-d-glucose, substrates for synthetic antigens

Abstract Synthesis of the title oligosaccharides was performed with the use of peracetylated l - glycero -β- d - manno -heptosyl trichloroacetimidate as the heptosyl donor and (oligo)glucosyl acceptors bearing acyl and acetal protecting groups.

Five monophosphates of methyl l-glycero-α-d-manno-heptopyranoside: synthesis, hydrolysis and migrations

Abstract From suitably protected methyl α - d -mannopyranosides five methyl l - glycero - α - d - manno -heptopyranosides were synthesized by the one-carbon-atom chain elongation at C-6 and converted to five monophosphates ( 1–5 ) having the PO(OH) 2 group at O-2, -3, -4, -6 and -7. Compounds 1–5 were exposed to acidic and basic hydrolytic conditions used in lipopolysaccharide analysis and the products and their proportion were determined. Under acidic conditions, besides hydrolysis of the glycoside, migrations and hydrolytic cleavage of the phosphate residue were found. Under basic conditions the phosphates were stable.

Benzyl 7-O-allyl-2,3-O-isopropylidene-4-O-p-methoxybenzyl-l-glycero-α-d-manno-heptopyranoside, a versatile ld-manHepp derivative☆

Abstract Benzyl 2,3- O -isopropylidene-4- O - p -methoxybenzyl-α- d -mannopyranoside was oxidized according to Swern, and the aldehyde obtained was treated with allyloxymethylmagnesium chloride to yield the title heptose derivative ( 7 ) as the main product. This compound had the hydroxyl group at C-6 free. Benzylation yielded the fully protected derivative 9 . O -Deallylation furnished a heptose derivative ( 10 ) having the C-7 hydroxyl group free. Similarly, removal of the p -methoxybenzyl group from 9 led to a derivative ( 11 ) with the C-4 hydroxyl group free. Acid hydrolysis of 9 under controlled conditions led to 2,3-diol ( 12 ). This compound was benzylated under two-phase conditions to yield the 2- O -benzylated product ( 13 ) having a free OH group at C-3. Benzylation of the stannylene derivative obtained from the 2,3-diol and dibutyltin oxide gave the 3- O -benzyl derivative ( 14 ) with HO-2 free. The yields of all steps are good to very good.

The synthesis of five l-glycero-d-manno-heptose monophosphates

Abstract From suitably protected benzyl α- d -mannopyranosides, five benzyl l -glycero-α- d -manno-heptopyranosides were synthesized by chain-elongation at C-6. By regiospecific protection-deprotection procedures five O-benzylated heptosides having ‘isolated’ free OH groups at C-2, C-3, C-4, C-6, or C-7 were obtained. These substrates were phosphorylated and the products were converted into free monophosphates or monophosphate cyclohexylammonium salts (1–5) which were characterized by 1H, 13C, and 31P NMR spectra and high-performance anion-exchange chromatography.

Solid‐Phase [2+2] Cycloadditions between Chlorosulfonyl Isocyanate and Chiral Vinyl Ethers

Vinyl ethers 10, 23, and 33 were attached to Wang resin through the p-oxyphenylsulfonyl linker. The [2+2] cycloadditions between chlorosulfonyl isocyanate and the polymer-bound vinyl ethers 12, 24, and 34, followed by intramolecular alkylation of the β-lactam nitrogen atom, gave mixtures of the corresponding diastereomeric clavams 8/9 and 21/22 or the oxacephams 31/32, accompanied by the oxirane 7 or the oxetane 30, respectively. This cyclization/cleavage step was performed in the presence of the strong organic bases BEMP and DBU. The corresponding reaction sequences performed in solution provided the oxabicyclic β-lactams without the accompanying anhydrosugars. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

A practical preparation of the key intermediate for penems and carbapenems synthesis

A novel, practical and stereoselective synthesis of (3R,4R)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidinone, a key intermediate in the preparation of β-lactam antibiotics is reported. The crucial step of the synthesis is based on the Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade between silyl protected (R)-3-butyn-2-ol and the nitrone derived from benzyl hydroxylamine and benzyl glyoxylate. The obtained adduct is subjected to debenzylation with sodium, or lithium in liquid ammonia followed by oxidation with lead tetraacetate to afford the final product.

Distribution of pyranose and furanose forms of 6-deoxyheptoses in water solution.

On the basis of 1H and 13C NMR spectroscopy studies, the proportion of pyranose and furanose forms of 6-deoxyheptoses in water solution was determined. Water solution of 6-deoxyheptoses contains all possible furanose and pyranose forms (except 6-deoxy-gluco-heptose for which only pyranose was found), although pyranose is dominant.

From methyl d-glucopyranoside to methyl d-allopyranoside via the Mitsunobu reaction

Methyl β-d-glucopyranoside reacted with a 4-molar excess of the Mitsunobu reagents (triphenylphosphine–diethyl azodicarboxylate–benzoic acid) under Weinges et al. [Carbohydr. Res., 164 (1987) 453–458] conditions to furnish four differently benzoylated methyl β-d-allopyranosides in a very good overall yield. The same reaction applied to methyl α-d-glucopyranoside yielded allosides in a low yield and nine other sugar products. These results give an insight into the course of the Mitsunobu esterification–inversion reaction.