RESUMO
An efficient protocol for calculating 13C NMR chemical shifts for natural products with multiple degrees of conformational freedom is described. This involves a multistep procedure starting from molecular mechanics and ending with a large basis set density functional model to obtain accurate Boltzmann conformer weights, followed by empirically corrected density functional NMR calculations for the individual conformers. The accuracy of the protocol (average rms <4 ppm) was determined by application to â¼925 diverse natural products, the structures of which have been confirmed either by X-ray crystallography or independent synthesis. The protocol was then applied to â¼ 2275 natural products, the structures of which were elucidated mainly by NMR and MS data. Five to ten percent of the latter compounds exhibited rms errors significantly in excess of 4 ppm, suggesting possible structural or signal assignment errors. Both data sets are available from an online browser ( NMR.wavefun.com ). The procedure can be and has been fully automated and is practical using present-generation personal computers, requiring a few hours or days depending on the size of the molecule and number of accessible conformers.
Assuntos
Produtos Biológicos/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13/métodos , Cristalografia por Raios X , Teoria da Densidade Funcional , Conformação MolecularRESUMO
The previously published structure of the fungal metabolite acremine P is revised by re-evaluation of chemical shift values and NOESY data, and by DFT calculations.
Assuntos
Acremonium/química , Organismos Aquáticos/química , Terpenos/química , Vias Biossintéticas , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Imageamento Tridimensional , EstereoisomerismoRESUMO
The structures of epoxyroussoenone (1) and epoxyroussoedione (3) isolated from a culture broth of Roussoella japanensis KT1651 were determined. Although NMR spectra provided insufficient structural information, computation of the theoretical chemical shifts with DFT EDF2/6-31G* enabled us to elucidate not only the planar structure, but also the relative configuration. Their ECD (electric circular dichroism) spectra suggested the absolute configurations, which were confirmed with time-dependent DFT calculations employing BHandHLYP/TZVP. The ECD calculations for other stereoisomers yielded obviously different spectral profiles, thus confirming the relative structures of 1 and 3.
Assuntos
Ascomicetos/química , Compostos de Epóxi/química , Compostos de Epóxi/isolamento & purificação , Compostos de Epóxi/farmacologia , Fungos/efeitos dos fármacos , Japão , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , EstereoisomerismoRESUMO
Structural features of hydrogen thioperoxide (oxadisulfane, H-S-O-H) and of alkanesulfenic acids (R-S-O-H; R = CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CF3, CCl3) and the mechanisms of their dehydrative cyclocondensation to the respective sulfinothioic acid (H-(SâO)-S-H) and alkyl alkanethiosulfinates (R-(SâO)-S-R) have been studied using coupled cluster theory with single and double and perturbative triple excitations [CCSD(T)] and quadratic configuration interaction with single and double and perturbative triple excitations [QCISD(T)] with the cc-pVDZ basis set and also using second-order Møller-Plesset perturbation theory (MP2) and the hybrid density functionals B3LYP, B3PW91, and PBE1PBE with the 6-311+G(d,p) basis set. The concerted cyclodehydration mechanisms include cyclic five-center transition states with relatively long distance sulfur-sulfur bonding interactions. Attractive and repulsive nonbonding interactions are predicted in the sulfenic acids, transition states, and thiosulfinates. In the alkyl alkanethiosulfinates attractive cyclic C-H----OâS nonbonding interactions are predicted. CCSD(T) and QCISD(T) predict similar values for the relative energies and CCSD(T) predicts the barrier to the cyclocondensation of H-S-O-H to sulfinothioic acid (H-(SâO)-S-H) to be 41.8 kcal/mol, and barriers in the range of 37.5 to 39.6 kcal/mol are predicted for the condensation of alkanesulfenic acids to alkyl alkanethiosulfinates.
Assuntos
Alcanos/química , Peróxidos/química , Ácidos Sulfênicos/química , Ciclização , Desidratação , Teoria QuânticaRESUMO
The first total synthesis of roquefortine C is achieved by implementation of a novel elimination strategy to construct the thermodynamically unstable E-dehydrohistidine moiety. Molecular modeling studies are presented which explain the instability of the roquefortine C structure compared to that of isoroquefortine C.
Assuntos
Indóis/síntese química , Ascomicetos/química , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Histidina/análogos & derivados , Histidina/química , Ligação de Hidrogênio , Imidazóis/síntese química , Imidazóis/química , Indóis/química , Modelos Moleculares , Conformação Molecular , Piperazinas/síntese química , Piperazinas/química , TermodinâmicaRESUMO
Norneolambertellin (1) was isolated from a mycoparasite Lambertella sp. 1346. Combined analysis of the NMR spectra and chemical shift prediction based on molecular orbital calculation successfully revealed a novel pyrano[3,2-c]chromene-2,5-dione structure, which was further confirmed by X-ray crystallographic analysis. Isotopomer distribution analysis of the sample, prepared under labeling conditions, deduced its biosynthetic pathway.