The solid-state and solution-state reassigned structures of tagitinin A, a 3,10-epoxy-germacrolide from Tithonia diversifolia, and the interconversion of 3,10-epoxy-germacrolide conformational families via a ring-atom flip mechanism

Abstract

Tagitinina A(2), uma 3,10-epoxi-germacrolida-6,7-trans-lactona conhecida e isolada de Tithonia diversifolia foi estudada através de difração de raios-X de monocristal. Verificou-se que a mesma apresenta a configuração relativa 1 ,4 ,6 ,7 ,8 que difere da orientação 1 em C(1) proposta originalmente na literatura e que foi determinada pelo método de Horeau. Análise do espectro de 1 H-RMN de 2 em solução de d6-acetona mostra que a molécula mantém a conformação twist-chair-boat (TCB) observada cristalograficamente para o anel de 9 membros. As conformações twist-chairboat/skew-chair-boat do tipo 3 para anéis de 9 membros saturados e insaturados dentro das 3,10-epoxi-germacrolídas podem ser convertidas à conformação skew-chair-chair (SCC) através de mecanismo de inversão de C(9) do anel. Como resultado dessa mudança conformacional, a orientação de C(1) e de C(8) da unidade oxicarbonila são transformados de diequatorial para diaxial. A estereoquímica relatada para lactonas do tipo 3,10-epoxi-germacrolida e resultados de modelagem utilizando-se DFT B3LYP/6-31g(d) indicam que os átomos C(1) tetraédricos estabilizam conformações TCB/SCB do tipo 3 enquanto que aqueles com geometria trigonal estabilizam a conformação SCC.Tagitinin A (2), a known 3,10-epoxy-germacrolide-6,7-trans-lactone isolated from Tithonia diversifolia, was investigated by single crystal X-ray diffraction analysis. It was found to have a 1 ,4 ,6 ,7 ,8 relative configuration which differed at C(1) from the 1 -orientation originally reported in the literature which was determined by Horeau's Rule. Analysis of the 1H NMR spectrum of 2 shows the molecule to maintain its crystallographically observed twist-chair-boat (TCB) ninemembered ring conformation in acetone-d6 solution. The twist-chair-boat/skew-chair-boat type 3 conformations of saturated/unsaturated nine-membered rings within 3,10-epoxy-germacrolides can be interconverted to the skew-chair-chair (SCC) conformation by means of a C(9) ring atom flip mechanism. As a result of this conformational change, the orientation of the C(1) atom and the C(8)-oxycarbonyl moiety are transformed from diequatorial to diaxial. The reported stereochemistry of 3,10-epoxy-germacrolide lactone structures, and the DFT B3LYP/6-31g(d) modeling findings in this work indicate that tetrahedral C(1) atoms stabilize the TCB/SCB type 3 conformations, while their trigonal counterparts stabilize the SCC conformation.

Insecticidal activity of Tithonia diversifolia and Vernonia amygdalina

“…(Figure 1). The NMR data were broadly in agreement with published data for tagitinin A in acetone-d 6 (Glaser et al 2005), and in CDCl 3 (García et al 2006). In acetone-d 6 no evidence of isomerisation could be observed based on a additional 1D proton spectra after the acquisition of all the other spectra (1D 13 C and 2D).…”

Absolute Configuration of Clemateol

“…The aqueous residue was extracted with dichloromethane (3 × 15 mL) and the organic layer was dried with anhydrous sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography column using a 15% ethyl acetate solution in hexane as eluent, yielding 2 as a colorless oil (713 mg, 89% 3 , C-1'), 22.6 (CH 3 , C-1), 22.9 (CH 3 , C-5"), 24.6 (CH 3 , C-5'), 40.3 (C, C-5), 60.5 (CH, C-2), 64.6 (CH, C-3), 74.9 (CH, C-4), 112.9 (CH 2 , C-7), 144.0 (CH, C-6).…”

“…The organic solution was washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated. The crude material was purified by flash chromatography column using as eluent a solution of 10% ethyl acetate in hexane to render ketone 7 as oil (92 mg, 55% 3 , C-5"), 22.6 (CH 3 , C-5'), 23.6 (CH 3 , C-1'), 24.1 (CH 3 , C-1), 49.8 (C, C-5), 61.3 (CH, C-2), 63.2 (CH, C-3), 115.1 (CH 2 , C-7), 141.3 (CH, C-6), 206.1 (C, C-4).…”

“…As in the case of R L and R S in clemateol, little stereo-differentiation between the large and small substituent may complicate the analysis and compromise the result (Figure 1). 3 In order to validate the method previously used or even to correct the absolute configuration proposed earlier, the absolute configuration of C-3 and C-4 of clemateol was unequivocally established on the basis of detailed nuclear magnetic resonance (NMR) spectroscopic data and resonance scattering effects in its single crystal X-ray diffraction analysis. Initially, the relative configuration of C-3 and C-4 was determined by analysis of the H-H coupling constant H-3 and H-4 in the 3,4-acetonide (4) obtained from its diol-derivative (3).…”

“…3 In order to validate the method previously used or even to correct the absolute configuration proposed earlier, the absolute configuration of C-3 and C-4 of clemateol was unequivocally established on the basis of detailed nuclear magnetic resonance (NMR) spectroscopic data and resonance scattering effects in its single crystal X-ray diffraction analysis. Initially, the relative configuration of C-3 and C-4 was determined by analysis of the H-H coupling constant H-3 and H-4 in the 3,4-acetonide (4) obtained from its diol-derivative (3). Subsequently, the absolute configuration of C-4 was determined by the method of Mosher, 4 using the Dd RS values of the (R and S)-MPA-esters, of clemateol derivatives 5 and 6.…”