3′,4-Di-O-methylcedrusin: synthesis, resolution and absolute configuration

Abstract

The title compound has been synthesised in racemic form by a biomimetic reaction sequence. The two enantiomers were resolved by column chromatography of one of the synthetic intermediates. On the basis of CD results a tentative absolute configuration for the synthetic enantiomers and natural 3',4-di-0methylcedrusin is proposed.Sungre de drug0 (dragon's blood), a blood-red latex produced by various South American Croton species, is widely used in local medicine for its wound-healing properties and as an anticancer agent . 3',4-Di-0-methylcedrusin or 3-[2-( 3,4-dimethoxyphenyl)-3-hydroxymethyl-7-methoxy-2,3-dihydro-1 -benzofuran-5-yl]propan-l-015 has been shown to be one of the active principles being a wound healing agent and an inhibitor of thymidine incorporation in endothelial cells. p 2 Results and discussionRacemic 5 has been synthesised as shown in Scheme 1. Near quantitative esterification of ferulic acid was achieved with a heterogeneous polymer catalyst to give methyl ferulate 1 the biomimetic 6,7 oxidative coupling of which, in the presence of silver oxide,8 to generate the dihydrobenzofuran skeleton is the crucial step in the reaction sequence. Compound 2, shown unequivocally by X-ray crystallography to have a transconfiguration,' upon attempted methylation with diazomethane or with dimethyl sulfate gave complex mixtures of unidentified compounds. With methyl iodide, however, it gave compound 3, although to avoid the formation of, for instance, C-methylated side products (the formation of a product with a molecular weight of 442 has been demonstrated by DCI-mass spectrometry) the reaction time has to be kept relatively short; this results in relatively low product yields. Hydrogenation of the double bond of 3 in the presence of Pd-C yields compound 4 almost quantitatively, although, prolonged reaction times or large amounts of catalyst have to be avoided, since they result in ring opening of the dihydrofuran ring. LiAlH, reduction of both ester functions of 4 gave 3',4-di-O-methylcedrusin 5.The structures of compounds 2 to 5 were established on the basis of 'H NMR-, 13C NMR-, COSY, and HETCOR-spectral evidence (Tables 1 and 2). Both natural 3',4-di-O-rnethylcedrusin and the racemic ' F1 m id 2: -I XI 9

Antioxidant and Anti-nitric Oxide Components from <i>Quercus glauca</i>

“…The absolute configuration of 2 was determined by analysis of its CD spectrum, where the CD curve with negative Cotton effects at λ max 241 and 293 nm was similar to that of (7R,8S)-4-O-methyldihydrodehydrodiconiferyl alcohol. 27) Consequently, the absolute stereochemistry of C-7 and C-8 were R and S, respectively and compound 2 was identified as (7R,8S)-dihydrodehydrodiconiferyl alcohol 4-β-D-xyloside.…”

Aromatic Constituents from the Heartwood of Santalum album L.

“…2). The absolute structures of many dihydrobenzo[b]furan-type neolignans have been assigned 21,[40][41][42][43] on the basis of the CD results of Achenbach et al 44) However, Antus et al 45) re- …”

Chemical Constituents in the Leaves of Vateria indica

“…Lemiere et al reported that the configurations at C-7 and C-8 of the dihydrobenzofuran skeleton can be distinguished in the range of 220-240 nm by CD spectroscopy. 18) We reported the CD evidence of (Ϫ)-e-viniferin and its oxidative derivative [(2R,3R)-3-(3,5-dihydroxyphenyl)-6-hydroxy-2-(4-hydroxyphenyl)-2,3-dihydrobenzofuran-4-carbaldehyde: 39] [negative Cotton effect at 236-237 nm].…”