Xanthones from Halenia corniculata. 3. Preparation of Standard 1-Hydroxy-2,3,4,5-tetramethoxyxanthone

Abstract

1-Hydroxy-2,3,4,5-tetramethoxyxanthone, which is used as a standard for quantitative determination of the total content of γ-pyrones, was isolated from the aerial part of Halenia corniculata L. Cornaz., an available raw material in Russia. A method for preparing standard 1-hydroxy-2,3,4,5-tetramethoxyxanthone was developed.We previously proposed a method for quantitative determination of the total content of γ-pyrones in the aerial part of Halenia corniculata L. Cornaz. [1]. The standard sample in this method was 1-hydroxy-2,3,4,5-tetramethoxyxanthone (1), which is the dominant component of the xanthones in the aerial part of H. corniculata. Several methods for preparing 1 are known: from roots and the aerial part of Swertia bimaculata Hf. & T. in 0.003% yield [2]; from roots of Frasera caroliniensis Walt., in 0.07% yield [3]; and from roots and the aerial part of H. asclepidea (HBK) Don, H. elliptica D. Don, and H. campanulata in yields of 0.10, 0.12, and 0.13%, respectively [4-6].Drawbacks of these methods are the unavailability of the raw material, the low yields (0.003-0.13% per mass of absolute dry raw material), and the duration and labor-intensiveness of the process.The goal of the present work was to develop a method for preparing standard 1 from the aerial part of H. corniculata growing in Russia.Several methods for preparing 1 were studied during the course of the work. Method 1 produced 1 in 0.04% yield. Methods 2-4 under the same conditions but using different eluents for column chromatography also isolated 1 in yields of 0.25, 0.12, and 0.04%, respectively. Method 5 involves simultaneous extraction of raw material and hydrolysis by HCl (2%). The resulting product (0.02% yield) was contaminated with oleanolic acid, which interferes with the separation and preparation of 1 as a pure compound.Method 2 gave the highest yield of 1 from the aerial part of H. corniculata and was used to produce three batches of 1. The content of 1 as determined by HPLC was 95.31-96.87% (Fig. 1). The compounds were identified using TLC, melting points, and UV and PMR spectroscopies. The physicochemical properties of the final product were analogous to those of chemically pure 1.

Concise approach to 1,4-dioxygenated xanthones via novel application of the Moore rearrangement

“…8b The 1 H NMR spectral data of 1 are in close accord with those reported for the isolated natural product, but there are some significant differences in the 13 C NMR data. 14 A xanthone that has been referred to as dulcisxanthone C was reported to have the structure of 46 ; 15 however, the 1 H and 13 C NMR spectral data reported for dulcisxanthone C do not match those for synthetic 46 , the structure of which was verified by single crystal x-ray crystallography. 16 Comparison of the 1 H and 13 C NMR spectral data of dulcisxanthone C actually correspond well to those obtained for synthetic 1 .…”

General and Expedient Synthesis of 1,4-Dioxygenated Xanthones

“…The present synthesis of 5 in seven steps and in 22% overall yield represents a significant improvement over the prior art . Although the 1 H NMR spectral data for synthetic 5 are consistent with those found in the literature, , there are some notable differences in the 13 C NMR data that have been reported for 5 . A compound that was named dulcisxanthone C and assigned the structure 22 has been isolated, but the spectral data for synthetic 22 , the structure of which was also verified by X-ray crystallography, do not match those reported .…”