RESUMO
Eribulin mesylate, one of the most synthetically challenging drugs to date, possesses 19 stereocentres in its structure and ascertaining the absolute stereochemistry at every stage of the 64-stage synthesis is crucial. In our quest to synthesize eribulin, we identified two critical building blocks of this molecule, namely 3,4:6,7-di-O-cyclohexylidene-D-glycero-α-L-talo-heptopyranose methanol monosolvate, C19H30O7·CH3OH, and (2R,3R,4R,5S)-5-allyl-2-[(S)-2,3-dihydroxypropyl]-4-[(phenylsulfonyl)methyl]tetrahydrofuran-3-ol, C17H24O6S, for which two-dimensional NMR (2D-NMR) data were not sufficient to prove the absolute configuration. To ensure structural integrity, single-crystal X-ray diffraction data were obtained to confirm the structures. This information provides useful insights into the structural framework of the large eribulin mesylate molecule.
Assuntos
Compostos Alílicos/química , Compostos Alílicos/classificação , Antineoplásicos/química , Cicloexenos/química , Furanos/química , Furanos/síntese química , Cetonas/síntese química , Monossacarídeos/química , Antineoplásicos/farmacologia , Cristalografia por Raios X , Furanos/farmacologia , Ligação de Hidrogênio , Cetonas/química , Cetonas/farmacologia , Espectroscopia de Ressonância Magnética , Difração de Raios XRESUMO
A toxicologic and dermatologic review of allyl alpha-ionone when used as a fragrance ingredient is presented.
Assuntos
Compostos Alílicos/toxicidade , Cicloexenos/toxicidade , Perfumes/toxicidade , Compostos Alílicos/classificação , Compostos Alílicos/farmacocinética , Animais , Qualidade de Produtos para o Consumidor , Cicloexenos/classificação , Cicloexenos/farmacocinética , Relação Dose-Resposta a Droga , Humanos , Testes de Mutagenicidade , Mutagênicos/classificação , Mutagênicos/farmacocinética , Mutagênicos/toxicidade , Perfumes/classificação , Perfumes/farmacocinética , Medição de Risco , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea , Testes de Irritação da Pele , Testes CutâneosRESUMO
The Raman spectra of several pairs of alkenyl methyl ethers of general structure R(1)R(2)C=CR(5)C(R(3)R(4))OCH3 and R(1)R(2)C(OCH3)C(R(5))=CR(3)R(4) (R(1), R(2), R(3), R(4), R(5) = H or C(n)H(2n+1), n = 1-3) are reported and discussed, with a view to establishing whether Raman spectroscopy offers a viable means of distinguishing between these isomeric unsaturated species. Key bands associated with the nu(sp2C-H) and nu(C=C) stretching modes are found to be particularly useful in this connection: R(1)R(2)C=CHCH2OCH3 and R(1)R(2)C(OCH3)CH=CH2 ethers (R(1), R(2) = CH3, C2H5) are easily distinguished on this basis. Differentiation of their lower homologues, R(1)CH=CHCH2OCH3 and R(1)CH(OCH3)CH=CH2 (R(1) = CH3, C2H5, C3H7), by similar means is also quite straightforward, even in cases where cis and trans isomers are possible. Pairs of isomeric ethers, such as CH3CH=C(CH3)CH2OCH3 and CH3CH(OCH3)C(CH3)=CH2, in which the structural differences are more subtle, may also be distinguished with care. Deductions based on bands ascribed to the stretching vibrations are usually confirmed by consideration of the signals associated with the corresponding delta(sp2C-H) deformation vibrations. Even C2H5CH=CHCH(C3H7)OCH3 and C3H7CH=CHCH(C2H5)OCH3 are found to have distinctive Raman spectra, but differentiation of these closely related isomers requires additional consideration of the low wavenumber region.
Assuntos
Compostos Alílicos/química , Éteres Metílicos/química , Compostos Alílicos/classificação , Isomerismo , Éteres Metílicos/classificação , Estrutura Molecular , Análise Espectral RamanRESUMO
THF solutions of the cationic chiral 1,3-diphenylallyl bidentate phosphine complexes [Pd(eta(3)-PhCHCHCHPh)(Duphos)](CF(3)SO(3)), Duphos = 1,2-Bis-((2R,5R)-2,5-dimethylphospholano)benzene), 2, and [Pd(eta(3)-PhCHCHCHPh)(P,S)]BF(4), 4, P,S = [8-((o-(diphenylphosphino)benzyl) thiomethyl]-(7,7'-dimethyl)-exo-norborneol, have been studied via pulsed gradient spin-echo (PGSE) diffusion, (1)H, (19)F HOESY and a variety of other multi-dimensional NMR methods. On the basis of the (1)H, (19)F HOESY data, the anions show a preference for a specific structural position with respect to the eta(3)-PhCHCHCHPh allyl ligand, i.e. the anion does not move evenly around the periphery of the cation. THF is shown to promote significant ion pairing, although neither 2 nor 4 shows 100% ion pairing.