Estudos visando a elucidação estrutural do alcaloide parviestemoamida : sintese (+/-)-10-epi- parviestemoamida

AUTOR(ES)
DATA DE PUBLICAÇÃO

2005

RESUMO

(-)-Parvistemoamide, a member of the Stemona alkaloids was reported by Xu and coworkers in 1991 as a minor alkaloid fram the roots of Stemona parviflora. Extracts of the Stemonaceae species have been used in Chinese and Japanese folk medicine as insecticides, antihelmintics for domestic animaIs and drugs for the treatment of human respiratory diseases such as bronquitis, pertussis, and tuberculosis. During our literature search, we found that the structure of (-)-parvistemoamide has been represented either as 1 or 2 (Figure 1) and we decided to unambiguously estabIish its structure by total synthesis. The strategy employed by us features the Michael addition af 3-methyl-2-silyloxydiene 20, prepared in 99% yield from commercially available 3-methyl-2(5H)-furanone (21), to acrylonitrile to afford 3,5-disubstituted d-butyrolactone (±)-18 in 91% yield. Treatment of a,b-unsaturated lactone (±)-18 with nitroester 19 in DBU (0.1 equiv)/CH3CN/rt afforded (±)-49 in 60% yield as an equimolar mixture of diastereoisomers at C9a. Compound (±)-17 was directly obtained as a single diastereomer by reaction of (±)-18 with nitroester 19 in the presence of 2 equiv. of DBU under reflux by a novel tandem Michael-Nef reaction or under oxidative conditions (KMnO4/SiO2) from (±)-49. The stereochemical assignment of (±)-49 was determined after its conversion to ketone (±)-17. The successfull completion of the synthesis of the parvistemoamide skeleton was achieved by one-pot hydrogenation of the cyano and ketone moieties in (±)-17 using PtO2/HOAc, followed by aIkaline work-up, to afford a diastereomeric mixture in C9a of (±)-10-epi-1 and (±)-2 (ratio 5:1) (Scheme 1). The relative configuration of the major product was established as (±)-10-epi-1 by nOe experiments. Comparison of the H-NMR data for (±)-10-epi-1 with those for the natural product (-)-parvistemoamide reveals good agreement except for the C-NMR data of the methyl group at C10 (which appeared 3.1 ppm upfield in (±)-10-epi-1) and for the carbonyl groups. ln summary, we have so far accomplished an efficient and diastereoselective construction of (±)-10-epi-1 parvistemoamide [(±)-10-epi-1] using three Michael reactions as key steps. The three stereocenters contained in the lactone ring could be simultaneously obtained total diastereoselectivity from (±)-18. Synthetic (±)-10-epi-1 was obtained in 5 steps and 8% overall yield via (±)-49 and in 4 steps and 11 % overall yield directly from (±)-18.

ASSUNTO(S)

stemona alcaloides sintese estereosseletiva parviestemoamida

ACESSO AO ARTIGO

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