排序方式: 共有15条查询结果,搜索用时 0 毫秒
1.
Treatment of 17-alkoxy-aspidospermidine derivatives with iodine and sodium hydroxide in methanolic or ethanolic solution yields the corresponding 17, 17-dialkoxy-17, 18-dihydro-1, 18-dehydro-aspidospermidine. Hence compounds 1 and 2 in methanol give the oxidation products 8 and 3 , respectively. In ethanol, 4 is converted to 5 , 2 to a mixture of 6 and 7 ; 4 in methanol yields a mixture of 6 and 7 in a different ratio. 相似文献
2.
Richard E. Shute David E. Jackson Barrie W. Bycroft 《Journal of computer-aided molecular design》1989,3(2):149-164
Summary The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3R-compounds possess notable Gram-positive antibacterial activity and potent-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retain-lactamase inhibitory activity.Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue. Comparative computer-assisted modelling of the 3R, and 3S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3R and the 3S-anilides was mutually exclusive. The conformational space for the more flexible benzylpenicillin could accommodate the side chains ofboth the constrained penicillin derivatives. By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3R-anilide and benzylpenicillin were identified. These conformers must be related to the antibacterial, bioactive conformer for the classical-lactam antibiotics. From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S2-subsite, specific for the side-chain aromatic moiety, and the 3-carboxylate functionality is presented.This work has been reported in preliminary form at the 4th Royal Society of Chemistry International Symposium on Recent Advances in the Chemistry of-lactam Antibiotics, Churchill College, Cambridge, U.K., 3–6 July 1988. 相似文献
3.
David E. Jackson Barrie W. Bycroft Trevor J. King 《Journal of computer-aided molecular design》1989,2(4):321-328
Summary X-ray crystallographic studies on synthetic DL-quisqualic acid and the corresponding carbon analogue have revealed pyramidal and almost planar geometries respectively for the ring nitrogen atoms carrying the alkyl side chain. Semi-empirical molecular orbital calculations on methyl-substituted model systems predict ring geometries in close agreement with experimentally observed data. The calculated energy barriers between the two enantiomeric forms (invertomers) of the oxadiazolidine systems along with some physical data would suggest that such forms are rapidly interconverting.Deceased. 相似文献
4.
van de Waal BW 《Physical review letters》1991,67(23):3263-3266
5.
Barber M Bell D Morris M Tetler L Woods M Bycroft BW Monaghan JJ Morden WE Green BN 《Talanta》1988,35(8):605-611
The characterization of components within actinomycin complexes may often be complicated by the lack of material and standards of known actinomycins. Mass spectrometry-mass spectrometry can be employed both as a separatory device and as a means of structural analysis. This technique has been applied to an actinomycin complex obtained from a previously unidentified Streptomyces strain. The method involved initial work on a known material, in this case actinomycin D, and application to the unknown material. Three major components within the unknown complex were characterized as actinomycins D, F(8), and F(9). 相似文献
6.
7.
Kira J. Weissman Matthew Bycroft Annabel L. Cutter Ulf Hanefeld Elizabeth J. Frost Máire C. Timoney Rebecca Harris Sandeep Handa Marc Roddis James Staunton Peter F. Leadlay 《Chemistry & biology》1998,5(12):743-754
Background: Modular polyketide synthases (PKSs) catalyse the biosynthesis of complex polyketides using a different set of enzymes for each successive cycle of chain extension. Directed biosynthesis starting from synthetic diketides is a potentially valuable route to novel polyketides. We have used a purified bimodular derivative of the erythromycin-producing polyketide synthase (DEBS 1-TE) to study chain extension starting from a variety of diketide analogues and, in some cases, from the alternative acyl-CoA thioester substrates.Results: Chain initiation in vitro by DEBS 1-TE module 2 using a synthetic diketide analogue as a substrate was tolerant of significant structural variation in the starter unit of the synthetic diketide, but other changes completely abolished activity. Interestingly, a racemic β-keto diketide was found to be reduced in situ on the PKS and utilised in place of its more complex hydroxy analogue as a substrate for chain extension. The presence of a diketide analogue strongly inhibited chain initiation via the loading module. Significantly higher concentrations of diketide N-acetylcysteamine analogues than their corresponding acyl-CoA thioesters are required to achieve comparable yields of triketide lactones.Conclusions: Although a broad range of variation in the starter residue is acceptable, the substrate specificity of module 2 of a typical modular PKS in vitro is relatively intolerant of changes at C-2 and C-3. This will restrict the usefulness of approaches to synthesise novel erythromycins using synthetic diketides in vivo. The use of synthetic β-keto diketides in vivo deserves to be explored. 相似文献
8.
Knowledge-based design of bimodular and trimodular polyketide synthases based on domain and module swaps: a route to simple statin analogues. 总被引:4,自引:0,他引:4
A Ranganathan M Timoney M Bycroft J Cortés I P Thomas B Wilkinson L Kellenberger U Hanefeld I S Galloway J Staunton P F Leadlay 《Chemistry & biology》1999,6(10):731-741
BACKGROUND: Polyketides are structurally diverse natural products that have a range of medically useful activities. Nonaromatic bacterial polyketides are synthesised on modular polyketide synthase (PKS) multienzymes, in which each cycle of chain extension requires a different 'module' of enzymatic activities. Attempts to design and construct modular PKSs that synthesise specified novel polyketides provide a particularly stringent test of our understanding of PKS structure and function. RESULTS: We have constructed bimodular and trimodular PKSs based on DEBS1-TE, a derivative of the erythromycin PKS that contains only modules 1 and 2 and a thioesterase (TE), by substituting multiple domains with appropriate counterparts derived from the rapamycin PKS. Hybrid PKSs were obtained that synthesised the predicted target triketide lactones, which are simple analogues of cholesterol-lowering statins. In constructing intermodular fusions, whether between modules in the same or in different proteins, it was found advantageous to preserve intact the acyl carrier protein-ketosynthase (ACP-KS) didomain that spans the junction between successive modules. CONCLUSIONS: Relatively simple considerations govern the construction of functional hybrid PKSs. Fusion sites should be chosen either in the surface-accessible linker regions between enzymatic domains, as previously revealed, or just inside the conserved margins of domains. The interaction of an ACP domain with the adjacent KS domain, whether on the same polyketide or not, is of particular importance, both through conservation of appropriate protein-protein interactions, and through optimising molecular recognition of the altered polyketide chain in the key transfer of the acyl chain from the ACP of one module to the KS of the downstream module. 相似文献
9.
10.
A new chemical degradation of (–)-kopsine is described which completely confirms the structure of this alkaloid. Correlation of (–)-aspidofractinine, (–)-pleiocarpine and (–)-kopsine with (–)-minovincine establishes the absolute stereochemistry of these bases. It appears that, in contrast to the aspidospermine group, all alkaloids containing the aspidofractinine skeleton possess the same absolute stereochemistry. 相似文献