ABSTRACT
An Eryus sp. of marine sponge from the Great Australian Bight has yielded the first reported natural occurrence of a cyclonucleoside, N(3),5'-cycloxanthosine. The structure of N(3),5'-cycloxanthosine was confirmed by detailed spectroscopic analysis and total synthesis.
Subject(s)
Porifera/chemistry , Ribonucleosides/isolation & purification , Tryptophan/analogs & derivatives , Xanthines/isolation & purification , Animals , Australia , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Ribonucleosides/chemical synthesis , Ribonucleosides/chemistry , Tryptophan/chemical synthesis , Tryptophan/chemistry , Tryptophan/isolation & purification , Xanthines/chemical synthesis , Xanthines/chemistryABSTRACT
The synthesis of nine GPE* analogues, wherein the alpha-carboxylic acid group of glutamic acid has been modified, is described by coupling readily accessible N-benzyloxycarbonyl-glycyl-L-proline 2 with various analogues of glutamic acid. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glutamate residue on the observed neuroprotective properties of the endogenous tripeptide GPE.
Subject(s)
Glutamic Acid/analogs & derivatives , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/pharmacology , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Animals , Cells, Cultured , Corpus Striatum/cytology , Female , Glutamic Acid/chemical synthesis , Glutamic Acid/pharmacology , Models, Chemical , Molecular Structure , Neurons/drug effects , Okadaic Acid/antagonists & inhibitors , Rats , Rats, WistarABSTRACT
The synthesis of eight GPE* analogues, wherein the gamma-carboxylic moiety of the glutamic residue has been modified, is described by coupling readily accessible N-benzyloxycarbonyl-glycyl-L-proline with various analogues of glutamic acid. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glutamate residue on the observed neuroprotective properties of the endogenous tripeptide GPE.
Subject(s)
Glutamic Acid/analogs & derivatives , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/pharmacology , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Animals , Cells, Cultured , Corpus Striatum/cytology , Female , Glutamic Acid/chemical synthesis , Glutamic Acid/pharmacology , Models, Chemical , Molecular Structure , Neurons/drug effects , Okadaic Acid/antagonists & inhibitors , Rats , Rats, WistarABSTRACT
(1--> 1), (1--> 3) and (1--> 4) acetal-linked monocarba-disaccharides have been synthesised from a series of glucosylated gamma- and delta-lactonic acids prepared from common intermediate, obtained from the Diels-Alder reaction of maleic anhydride and (E)-1-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyloxy)-3-(trimethylsiloxy)buta-1,3-diene 1. Thiohydroxamic ester 14, prepared from gamma-lactonic acid 9, gave, upon treatment with tert-butyl thiol and light, the lactone 15. Subsequent lithium aluminium hydride reduction and acetylation gave the (1--> 3) acetal-linked monocarbadisaccharides 1,6-di-O-acetyl-3-O-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyl)-2,4-dideoxy-5a-carba-beta-L-threo-hexopyranose 16. In a similar manner, protected monocarba-disaccharides 13, 19, 30, and 35 possessing L-ido, L-xylo, D-arabino and L-ido configurations of the carba-pyranose ring have been prepared. Treatment of thiohydroxamic esters 14 and 17 with either tert-butyl thiol or trityl thiol, dimethyl sulfide, oxygen and light gave alcohols 20 and 22. Subsequent lithium aluminium hydride reduction and aceytlation gave the monocarbadisaccharides 1,4,6-tri-O-acetyl-3-O-[2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyl]-2-deoxy-5a-carba-beta-L-arabino-hexopyranose 21 and 1,2,4,6-tetra-O-acetyl-3-O-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyl)-5a-carba-beta-L-glucopyranose 23 respectively.
