S.D. Gero

Liquid crystalline 5,6-O-acetals of L-galactono-1,4-lactone prepared by a microwave irradiation on montmorillonite

Abstract Acetal derivatives of L-galactono-1,4-lactone showing thermotropic liquid crystalline properties were synthesized without sovent in the presence of dry montmorillonite KSF using microwave irradiation.

Interaction of synthetic D-6-deoxy-myo-inositol 1,4,5-trisphosphate with the Ca2+-releasing D-myo-inositol 1,4,5-trisphosphate receptor, and the metabolic enzymes 5-phosphatase and 3-kinase

The ability of D‐6‐deoxy‐myo‐inositol 1,4,5‐trisphosphate [6‐deoxy‐Ins(1,4,5)P3], a synthetic analogue of the second messenger D‐myo‐inositol 1,4,5‐trisphosphate [Ins(1,4,5)P3], to mobilise intracellular Ca2+ stores in permeabilised SH‐SY5Y neuroblastoma cells was investigated. 6‐Deoxy‐Ins(1,4,5)P3 was a full agonist (EC30 = 6.4 μM), but was some 70‐fold less potent than Ins (1,4,5)P3 (EC30 = 0.09 μM), indicating that the 6‐hydroxyl group of Ins(1,4,5)P3 is most important for receptor binding and stimulation of Ca2+ release, but is not an essential structural feature. 6‐Deoxy‐Ins(1,4,5)P3 was not a substrate for Ins (1,4,5)P3 5‐Phosphatase, but inhibited both the hydrolysis of 5‐[22P] + Ins (1,4,5)P3 (K 1 76 μM) and the phosphorylation of [3H]Ins(1,4,5)P3 (apparent K 1 5.7 μM) 6‐Deoxy‐Ins (1,4,5)P3 mobilized Ca2+ with different kinetics to Ins(1,4,5)P3, indicating that it is probably a substrate for Ins(1,4,5)P3 3‐kinase.

Synthetic methods for the preparation of basic D- and L-pseudo-sugars. Synthesis of carbocyclic analogues of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP)

Abstract Two exocyclic olefins 10 and 22 readily elaborated from D-glucosamine have been transformed by Ferrier rearrangement reaction into amino-cyclohexanones 11 12 and 23 24. Reduction of ketone 11 with tri-t-butoxy-aluminium hydride followed by sequential acetylation and hydrogenolysis gave the acid 14 which was coupled with dipeptide 15 to provide 16. Alkaline hydrolysis of the latter afforded 1 a carbocyclic nor-analogue of MDP. The second target molecule 2 was prepared from an oxazolidine-pseudo-D-glucosamine 27 obtained by treatment of amino-cyclohexanone 23 with methoxymethylenetriphenylphosphorane and mercuric acetate-sodium borohydride reagents as key steps in the synthesis. On the other hand hydroboration of the olefin 31 yielded pseudo-L-idosamine derivative 28. Birch reduction of 27 followed by sequential benzylidenation etherification with (S)-α-chloropropionic acid and condensation of the resulted 36 with dipeptide 15 gave 36. Hydrogenolysis of the latter afforded the carbocyclic analogue 2 of MDP.

Synthesis of optically active derivatives of myo-inositol : Preparation of 1 l-myo-inositol 1-phosphate

Abstract 1 l -1-O-toluene-p-sulphonyl-chiro-inositol 5 has been prepared by the selective de-O-methylation and de-cyclohexylidenation of 1 l -3,4:5,6-di-O-cyclohexylidene-2-O-methyl-1-O-toluene-p-sulphonyl-chiro-inositol obtained from quebrachitol, 1 l -2-O-methyl-chiro-inositol. This optically active toluene-p-sulphonyl derivative, which is by inversion at C-1, a potential source of optically active myo-inositol derivatives, has, after benzoylation, been converted into a mixture of 1 d -1,2,4,5,6-penta-O-benzoyl-myo-inositol and 1,3,4,5,6-penta-O-benzoyl-myo-inositol, which were separated. From the former, after phosphorylation and debenzoylation, 1 l -myo-inositol 1-phosphate, the product of the enzyme, glucose 6-phosphate-inositol 1-phosphate cyclase, was obtained as the crystalline dicyclohexylamine salt.

Synthesis of 5′,8-cyclopurine and of 5′,6-cyclodihydropyrimidine nucleosides using intramolecular radical cyclisation based on the aryl telluride radical exchange process.

Abstract The synthesis of C-cyclopurine and C-cyclodihydropyrimidine nucleosides has been effected using 5′-aryltelluronucleosides. Generation of methyl radicals from the photolysis of the acetyl derivative of N-hydroxy-2-thiopyridone permitted, by radical exchange, the formation of 5′-nucleoside radicals which cyclized in satisfactory yields.

Stereocontrolled radical reactions in carbohydrate and nucleoside chemistry.

Abstract The radicals, generated by photolysis of 2,3-dimethyl ketals of N-hydroxy-2-thiopyridone uronic esters, reacted stereoselectively with electron deficient olefins leading to highly functionalised chain-elongated pentafuranosides, hexapyranosides and pentafuranosyl-nucleosides through the 4,5 and 4′ radicals, respectively.

Stereoselective synthesis of 6-deoxy and 3,6-dideoxy-D-myo-inositol precursors of deoxy-myo-inositol phosphate analogues from D-galactose

The synthesis of chiral protected D-6-deoxy-myo-inositol derivatives from D-galactose is described. Ferrier rearrangement of hexenogalactopyranosides has been employed to produce the corresponding 6-deoxy-cyclohexanone polyols. The stereoselectivity of the carbocyclic transformation was discussed on the basis of the experimental data and a mechanism has been proposed. From deoxy-inososes, the access to a variety of 6-deoxy and 3,6-dideoxy-myo-inositol was performed to prepare suitable monool, diol and triol precursors for the synthesis of D-deoxy-myo-inositol phosphate analogues.

New synthesis of sugar, nucleoside and α-amino acid phosphonates

Abstract Photolysis of N-hydroxy-2-thiopyridone esters derived from uronic acids or α-amino acids in presence of vinyl phosphonate affords the corresponding phosphonate derivatives. A convenient route for the synthesis of the isostere of AZT-5′ monophosphate is described.

From carbohydrates to carbocycles: radical routes via Tellurium derivatives

Abstract D-Ribose was transformed to its protected tosylate 15 , followed by a Wittig-reaction to give 16 as a 3:1 mixture of the corresponding Z and E isomers. This mixture was then transformed to the aniseltelluride 17 and the latter cyclized in a radical exchange reaction to a mixutre of the carbocycles 18a and 18b (in a 17:2 ratio). The major product 18a was then transformed to various chiral cyclopentane derivatives including the cyclopentenone-derivative 23 . Various other carbohydrate-based approaches have also been explored.

A PRACTICAL DECARBOXYLATIVE HYDROXYLATION OF CARBOXYLIC ACIDS

Abstract Irradiation of esters of N-hydroxy-2-thiazolinethione under air or oxygen at room temperature in the presence of tert-dodecanethiol affords the corresponding nor-alcohols after a reductive work-up.