Navegando por Palavras-chave "Stereochemistry"

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    Absolute configuration reassignment of nectamazin A: Implications to related neolignans
    (Elsevier, 2023-08-21) Batista, Andrea Nastri de Luca; Santos, Carlos Henrique Totini dos; Albuquerque, Ana Carolina Ferreira de; Santos Jr, Fernando Martins dos; Garcez, Fernanda Rodrigues; Batista Jr, João Marcos [UNIFESP]; http://lattes.cnpq.br/4209224090500050
    The ability of nature to produce structurally complex molecules makes the determination of the absolute configu- ration of natural products a challenging task. Although extensive NMR analysis generally allows for the reliable assignment of relative configurations, the assignments of absolute stereochemistry are commonly performed by empirical comparisons of optical rotation (OR) and/or electronic circular dichroism (ECD) data obtained for related molecules. Such an approach, however, may lead to misassignments and consequent error propagations. Herein, we present the case of the bicyclo(3.2.1)octane neolignan named (+)-nectamazin A. This compound was first reported in 2009 from Nectandra amazonum Nees. (Lauraceae) and had its absolute configuration determined as 7R,8S,3′S,4′R,5′S by means of experimental ECD spectroscopy. Our chemical studies on Ocotea aciphylla (Lauraceae) led to the isolation of (+)-nectamazin A. The extensive analysis of OR, ECD, and vibrational CD data aided by quantum chemical cal- culations, however, indicated (+)-nectamazin A to have the 7S,8R,3′R,4′S,5′R absolute configuration, in conflict with the configuration reported in the literature. The cause of the original incorrect assignment of (+)-nectamazin A derives from the direct comparison of experimental OR and ECD data obtained for structurally related molecules with different chromophoric systems. As an alternative, VCD spectroscopy is presented as a more reliable and sensitive technique to stereochemical investigations of bicyclo(3.2.1)octane neolignans.
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    Conformational preferences induced by cyclization in orbitides: a vibrational CD study
    (Royal Society of Chemistry (RSC), 2022-01-18) Yokomichi, Maria Augusta Saemi [UNIFESP]; Silva, Hanyeny R. L.; Brandao, Lorenza E. V. N.; Vicente, Eduardo Festozo; Batista Junior, João Marcos [UNIFESP]; http://lattes.cnpq.br/4209224090500050
    Orbitides are bioactive head-to-tail natural cyclic peptides from plant species. Their bioactivity is intrinsically related to the main conformations adopted in solution, whose correct characterization represents an important bottleneck for medicinal chemistry applications. To date, NMR spectrosocopy has been the most frequently used technique to assess the secondary structure of orbitides. Despite the amount of structural information commonly available from NMR, its time scale frequently results in a limited conformational ensemble with a single mean structure, which may not represent the bioactive conformation. Additionally, problems with inter-residue NOE/ROE signals can reduce the accuracy and confidence of the 3D assignments. Vibrational circular dichroism (VCD), on the other hand, has been demostrated as a powerful tool to probe the stereostructure of chiral molecules, including peptides and proteins, with enhanced sensitivity to individual conformations in the condensed phase. Herein, we present the first VCD stereochemical investigation of orbitides. By combining IR/VCD experiments in ACN-d3 and ACN-d3/D2O mixtures with DFT calculations in different levels of theory we were able to determine the solution-state conformational behavior, as well as the main structural restraints induced by cyclization, of the seven-residue orbitide pohlianin A and its linear precursor. VCD results indicated inverse γ-turns as the most prevalent structural motif for the linear precursor in partially aqueous solution, while type I and type VI β-turns were induced by the cyclization process, along with some classic γ-turns. In addition to the conformation of the cyclic peptide already described from NMR data, two previously unidentified conformations with distinct secondary structures were found to significantly populate the sample. This conformational discriminatory power of VCD for both linear and cyclic peptides in different solvent systems may lead to more accurate structural characterization of turn-rich peptidic natural products and help the design of conformationally-tailored peptides for more precise structure–activity relationship results.
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    Plakilactone J: Structure and absolute configuration
    (Elsevier, 2022-11-12) Batista, Andrea Nastri de Luca; Brito, Mateus de Freitas; Batista Junior, João Marcos [UNIFESP]; Valverde, Alessandra Leda; http://lattes.cnpq.br/4209224090500050
    The chemical investigation of the Brazilian marine sponge Plakortis angulospiculatus led to the isolation of the new peroxide-derived polyketide plakilactone J (1). The structure of (-)-1 was established by means of HRMS and NMR analysis, while its absolute configuration was unambiguously determined as (4R,6R) by vibrational circular dichroism spectroscopy and density functional theory calculations.