Search

Vibrational circular dichroism (VCD) is one of the most powerful techniques to assess stereochemistry of chiral molecules in solution state. The need for quantum chemical calculations to interpret experimental data, however, has precluded its widespread use by non-experts. Herein, we propose the search and validation of IR and VCD spectral markers to circumvent the requirement of DFT calculations allowing for absolute configuration assignments even in complex mixtures. To that end, a combination of visual inspection and machine learning based methods is used. Monoterpene mixtures are selected for this proof-of-concept study.

The assignment of absolute configuration (AC) is a crucial step in the structural characterization of natural products, especially for those subjected to biological assays. Methods such as X-ray crystallography, stereocontrolled organic synthesis, nuclear magnetic resonance (NMR), and chiroptical spectroscopies are commonly used to determine the AC of chiral natural compounds. Even with these well-established techniques, however, unambiguous stereochemical assignments of natural products remain a challenge, resulting in an increasing number of structural misassignments being reported every year. Herein, we will present the main techniques that have been used in AC reassignments of natural products over the last 10 years, along with some selected examples. Special attention will be paid to the strengths and weaknesses of each approach. With this, we expect to provide the readers with critical information to help them to choose the appropriate methods for correct AC determinations.

This work describes the chromatographic fractionation of the aerial parts of Calea pinnatifida and the structural characterization and determination of the absolute configuration of the isolated compounds as well as their antitumor potential. The HPLC fractionation of the CH2Cl2 phase of the MeOH extract from the leaves of C. pinnatifida led to the isolation of two related sesquiterpene lactones (STLs): calein C (1) and calealactone B (2). Additionally, during the purification process, a derivative of calein C (3) was formed as a product of the Michael addition of MeOH. The structures of Compounds 1&ndash, 3 were established based on spectroscopic and spectrometric data, while the absolute stereochemistry was established by vibrational circular dichroism. In order to evaluate the effect of the conjugated double bonds on the cytotoxic activity of STLs, Compounds 1&ndash, 3 were tested against anaplastic (KTC-2) and papillary (TPC-1) thyroid carcinoma cells. Calein C was the most active of the STLs, and displayed activity against both KTC-2 and TPC-1. On the other hand, the calein C derivative (3) was the least cytotoxic of all the compounds tested. These results are promising and suggest the importance of studying sesquiterpene lactones isolated from C. pinnatifida in terms of antitumor activity, especially considering the effects of &alpha, &beta, unsaturated carbonyl systems.

Made available in DSpace on 2018-12-11T17:36:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-05-01. Added 1 bitstream(s) on 2019-10-09T18:33:08Z : No. of bitstreams: 1 S0103-50532018000501105.pdf: 2907602 bytes, checksum: ef8123c16f0caba93af7dd13a547df64 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Département Caractérisation et Élaboration des Produits Issus de l’Agriculture, Institut National de la Recherche Agronomique Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Piper gaudichaudianum Kunth (Piperaceae) accumulates gaudichaudianic acid, a prenylated benzopyran, as its major component. Interestingly, this trypanocidal compound occurs as a racemic mixture. Herein, transcriptomic investigations of Piper gaudichaudianum using the RNA-seq approach are reported, and from the analysis of the transcripts expressed it was possible to propose a complete biosynthetic pathway for the production of gaudichaudianic acid, including the steps that originate its precursor, p-hydroxybenzoic acid. Peperomia obtusifolia (L.) A. Dietr. (Piperaceae) also accumulates racemic benzopyrans, however, its chromanes originate from the polyketide pathway, while the chromenes from Piper derives from the shikimate pathway. Recent transcriptomic and proteomic studies of the former species did not identify polyketide synthases involved in the production of the benzopyran moiety, but revealed the expression of tocopherol cyclase, which may be responsible for the cyclization of the 3,4-dihydro-2H-pyran ring. The analysis of the enzymes involved in the secondary metabolism of Piper gaudichaudianum and the comparison with the data previously obtained from Peperomia obtusifolia can provide valuable information on how these compounds are biosynthesized. Instituto de Química Universidade Estadual Paulista (UNESP) Departamento de Química Universidade Federal de São Carlos (UFSCar) Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista (UNESP) Instituto de Química Universidade de São Paulo (USP) Instituto de Química Universidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista (UNESP) FAPESP: 2013/07600-3 Département Caractérisation et Élaboration des Produits Issus de l’Agriculture, Institut National de la Recherche Agronomique: 2014/25222-9 Département Caractérisation et Élaboration des Produits Issus de l’Agriculture, Institut National de la Recherche Agronomique: 2014/50316-7 Département Caractérisation et Élaboration des Produits Issus de l’Agriculture, Institut National de la Recherche Agronomique: 2015/07089-2 FAPESP: 2011/01003-8

Sao Paulo Research Foundation (FAPESP) National Council for Scientific and Technological Development (CNPq-Brazil) CNPq Chiral natural product molecules are generally assumed to be biosynthesized in an enantiomerically pure or enriched fashion. Nevertheless, a significant amount of racemates or enantiomerically enriched mixtures has been reported from natural sources. This number is estimated to be even larger since the enantiomeric purity of secondary metabolites is rarely checked in the natural product isolation pipeline. This latter fact may have drastic effects on the evaluation of the biological activity of chiral natural products. A second bottleneck is the determination of their absolute configurations. Despite the widespread use of optical rotation and electronic circular dichroism, most of the stereochemical assignments are based on empirical correlations with similar compounds reported in the literature. As an alternative, the combination of vibrational circular dichroism and quantum chemical calculations has emerged as a powerful and reliable tool for both conformational and configurational analysis of natural products, even for those lacking UV-Vis chromophores. In this review, we aim to provide the reader with a critical overview of the occurrence of enantiomeric mixtures of secondary metabolites in nature as well the best practices for their detection, enantioselective separation using liquid chromatography, and determination of absolute configuration by means of vibrational circular dichroism and density functional theory calculations. Fed Univ Sao Carlos UFSCar, Dept Chem, Rod Washington Luis S-N,Km 235, BR-13565905 Sao Carlos, SP, Brazil Fed Univ Sao Paulo UNIFESP, Inst Sci & Technol, R Talim 330, BR-12231280 Sao Jose Dos Campos, SP, Brazil Fed Univ Sao Paulo UNIFESP, Inst Sci & Technol, R Talim 330, BR-12231280 Sao Jose Dos Campos, SP, Brazil FAPESP: 2013/01710-1, 2014/25222-9, 2015/07089-2, 2016/23794-0]|CNPq: 108265/2017-0 Web of Science

A simple IR and VCD spectra-structure relationship is proposed for the determination of relative and absolute configurations of polyhydroxylated molecules using a series of styryl-pyrones as model compounds. Spectral signatures identified for free molecules and acetonide derivatives may be used for stereochemical assignments of related molecules without the aid of quantum-chemical calculations.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:48:49Z No. of bitstreams: 1 S0100-40422010000200017.pdf: 242505 bytes, checksum: 178d6611bc19b0615dbbe4e4a7a24d81 (MD5) Made available in DSpace on 2013-08-22T18:48:49Z (GMT). No. of bitstreams: 1 S0100-40422010000200017.pdf: 242505 bytes, checksum: 178d6611bc19b0615dbbe4e4a7a24d81 (MD5) Previous issue date: 2010-01-01 Made available in DSpace on 2013-09-30T19:10:48Z (GMT). No. of bitstreams: 2 S0100-40422010000200017.pdf: 242505 bytes, checksum: 178d6611bc19b0615dbbe4e4a7a24d81 (MD5) S0100-40422010000200017.pdf.txt: 22081 bytes, checksum: 5051bd1ddcb22e79dd8517f88ca4eb98 (MD5) Previous issue date: 2010-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:21:21Z No. of bitstreams: 2 S0100-40422010000200017.pdf: 242505 bytes, checksum: 178d6611bc19b0615dbbe4e4a7a24d81 (MD5) S0100-40422010000200017.pdf.txt: 22081 bytes, checksum: 5051bd1ddcb22e79dd8517f88ca4eb98 (MD5) Made available in DSpace on 2014-05-20T14:21:21Z (GMT). No. of bitstreams: 2 S0100-40422010000200017.pdf: 242505 bytes, checksum: 178d6611bc19b0615dbbe4e4a7a24d81 (MD5) S0100-40422010000200017.pdf.txt: 22081 bytes, checksum: 5051bd1ddcb22e79dd8517f88ca4eb98 (MD5) Previous issue date: 2010-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Phytochemical investigations on three Brazilian Lauraceae species from the Cerrado region of São Paulo State, Ocotea corymbosa (Meins) Mez., O. elegans Mez. and Persea pyrifolia Nees & Mart. ex Nees resulted in the isolation of flavonoids, an ester of the 4-O-E-caffeoylquinic acid, an aromatic sesquiterpene besides furofuran lignans. This is the first chemical study on the leaves of Ocotea elegans and O. corymbosa as well as the first report of non-volatile compounds from Persea pyrifolia. Universidade Estadual Paulista Júlio de Mesquita Filho Instituto de Química Departamento de Química Orgânica Instituto Nacional de Pesquisas da Amazônia Divisão de Química de Produtos Naturais Departamento de Produtos Naturais Centro de Biotecnologia da Amazônia Universidade Estadual Paulista Júlio de Mesquita Filho Instituto de Química Departamento de Química Orgânica

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:57:49Z No. of bitstreams: 1 S0102-695X2011000300008.pdf: 910644 bytes, checksum: 192e0d04ab09adec67218e861f8a07a8 (MD5) Made available in DSpace on 2013-08-22T18:57:49Z (GMT). No. of bitstreams: 1 S0102-695X2011000300008.pdf: 910644 bytes, checksum: 192e0d04ab09adec67218e861f8a07a8 (MD5) Previous issue date: 2011-06-01 Made available in DSpace on 2013-09-30T19:52:54Z (GMT). No. of bitstreams: 2 S0102-695X2011000300008.pdf: 910644 bytes, checksum: 192e0d04ab09adec67218e861f8a07a8 (MD5) S0102-695X2011000300008.pdf.txt: 21094 bytes, checksum: 086dfc0f288f4d5d32d92111ef5d698d (MD5) Previous issue date: 2011-06-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:20:57Z No. of bitstreams: 2 S0102-695X2011000300008.pdf: 910644 bytes, checksum: 192e0d04ab09adec67218e861f8a07a8 (MD5) S0102-695X2011000300008.pdf.txt: 21094 bytes, checksum: 086dfc0f288f4d5d32d92111ef5d698d (MD5) Made available in DSpace on 2014-05-20T14:20:57Z (GMT). No. of bitstreams: 2 S0102-695X2011000300008.pdf: 910644 bytes, checksum: 192e0d04ab09adec67218e861f8a07a8 (MD5) S0102-695X2011000300008.pdf.txt: 21094 bytes, checksum: 086dfc0f288f4d5d32d92111ef5d698d (MD5) Previous issue date: 2011-06-01 Anidro do Brasil Extracoes Ltda (Botucatu, SP, Brazil) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Myrcia uniflora Barb. Rodr., Myrtaceae, popularly known as pedra-hume-caá in Brazil, is sold as dry extracts in capsules or as tinctures for the treatment of diabetes mellitus. Previous phytochemical studies on this species described the occurrence of the flavonoids mearnsitrin and myricitrin. In the present study, the chromatographic profiles of M. uniflora leaves and commercial extracts were determined using HPLC-PAD. Myricitrin was used as an external standard in the development and validation of the HPLC method. The proposed method is simple, rapid and reliable and can be successfully applied in industry for standardization of herbs and phytomedicines commercialised in Brazil as pedra-hume-caá. Universidade Estadual Paulista Instituto de Química Departamento de Química Orgânica Anidro do Brasil Extrações Ltda Universidade Estadual Paulista Instituto de Química Departamento de Química Orgânica CNPq: 500185/2006-9

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:57:49Z No. of bitstreams: 1 S0102-695X2010000500021.pdf: 2582101 bytes, checksum: 307e10b1cec799783e4a488586faafe6 (MD5) Made available in DSpace on 2013-08-22T18:57:49Z (GMT). No. of bitstreams: 1 S0102-695X2010000500021.pdf: 2582101 bytes, checksum: 307e10b1cec799783e4a488586faafe6 (MD5) Previous issue date: 2010-11-01 Made available in DSpace on 2013-09-30T19:52:53Z (GMT). No. of bitstreams: 2 S0102-695X2010000500021.pdf: 2582101 bytes, checksum: 307e10b1cec799783e4a488586faafe6 (MD5) S0102-695X2010000500021.pdf.txt: 30063 bytes, checksum: 2040e1187b63cfbff7a75f521119ec6c (MD5) Previous issue date: 2010-11-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:20:56Z No. of bitstreams: 2 S0102-695X2010000500021.pdf: 2582101 bytes, checksum: 307e10b1cec799783e4a488586faafe6 (MD5) S0102-695X2010000500021.pdf.txt: 30063 bytes, checksum: 2040e1187b63cfbff7a75f521119ec6c (MD5) Made available in DSpace on 2014-05-20T14:20:56Z (GMT). No. of bitstreams: 2 S0102-695X2010000500021.pdf: 2582101 bytes, checksum: 307e10b1cec799783e4a488586faafe6 (MD5) S0102-695X2010000500021.pdf.txt: 30063 bytes, checksum: 2040e1187b63cfbff7a75f521119ec6c (MD5) Previous issue date: 2010-11-01 Anidro do Brasil Extracoes Ltda (Botucatu-SP, Brazil) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Ptychopetalum olacoides Benth., Olacaceae, popularmente conhecida como marapuama, muirapuama ou miriantã, é uma espécie nativa da região da Amazônia do Brasil. Extratos das cascas da planta são tradicionalmente usados por suas propriedades estimulantes e afrodisíacas, e frequentemente comercializados como constituinte de uma grande variedade de formulações fitoterápicas. O fracionamento por coluna cromatográfica aberta seguida por CLAE-UV/PAD das cascas do caule de três extratos comerciais de P. olacoides permitiram o isolamento de três substâncias comuns em todos os extratos analisados. Os compostos foram identificados por RMN como ácido vanílico, ácido protocatecuíco e teobromina. O ácido vanílico foi utilizado como marcador fitoquímico para P. olacoides e empregado como padrão externo no desenvolvimento e validação de um método de análise qualitativo e quantitativo rápido por CLAE. O valor da recuperação do método desenvolvido foi de 99,02% e os valores de LOD e LOQ foram 0,033 e 0,11 mg.L-1; respectivamente. O método descrito poderá ser empregado para a padronização de plantas, extratos ou fitoterápicos comercializados como marapuama. Ptychopetalum olacoides Benth., Olacaceae, popularly known as marapuama or muirapuama or miriantã, is a species native to the Amazonian region of Brazil. Extracts of the bark of the plant have been used traditionally for its stimulating and aphrodisiac properties and currently commercialised by the herbal industry as constituents in a wide range of phytomedicines. Fractionation by open column chromatography followed by preparative HPLC-UV/PAD of the stem bark and of three commercial extracts of P. olacoides allowed the isolation of three components that were common to all extracts analysed, and these were identified by NMR to be vanillic acid, protocatechuic acid and theobromine. Vanillic acid, which has been proposed as a phytochemical marker for P. olacoides, was employed as an external standard in the development and validation of a rapid qualitative and quantitative HPLC assay for the analyte. The recoveries values of the developed method were 99.02% and the LOD and LOQ values were 0.033 and 0.11 mg.L-1, respectively. The described method may be applied to the standardisation of herbs, extracts or phytomedicines commercialised as marapuama. Universidade Estadual Paulista Instituto de Química Anidro do Brasil Extrações Ltda Universidade Estadual Paulista Instituto de Química CNPq: 500185/2006-9