The method of obtaining and bacteriochlorophyll

 

(57) Abstract:

The invention relates to the chemistry of biologically active compounds and is used in photodynamic therapy of cancer. Bacteriochlorophyll and extracted with dioxane and subsequent transfer of the pigment in petroleum ether. The target product is separated with decreasing content of dioxane in petroleum ether. Carry out cleaning of the target product by presidenial of bacteriochlorophyll and chlorinated hydrocarbons saturated hydrocarbons. The method allows to increase the yield of the target product and reduce its cost.

The invention relates to the chemistry of biologically active compounds and relates to improvements in method of producing bacteriochlorophyll a, which is used as feedstock for creating second generation sensitizers for photodynamic therapy of cancer.

Bacteriochlorophyll a is the complex molecule tetrahydropapaverine:

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Known only way to get bacteriochlorophyll a, based on the extraction of pigments methanol from biomass purple phototrophic bacteria of the genera Rhodopseudomonas viridis and Rhodospirillum rubrum, the evaporation of the extract under vacuum, followed ochistka method as follows:

1) large losses of bacteriochlorophyll a stages of evaporation and chromatographic purification due to intensive oxidation,

2) the high cost and complexity of high performance liquid chromatography

3) low productivity and output process bacteriochlorophyll a.

The aim of the invention is an improved method of producing bacteriochlorophyll a and increase its output.

This goal is achieved as follows.

The biomass of purple photosynthetic bacteria Rhodopseudomonas capsulata pour dioxane, stirred and centrifuged. The resulting solution was diluted with petroleum ether and shaken in a separating funnel. Formed two layers. The lower water-dioxane layer contains a water-soluble substances from the extract, the top - bacteriochlorophyll a, carotenoids, lipids, and other fat-soluble products. The light fraction is separated and diluted with two volumes of water. When shaken, the dioxane is redistributed from petroleum ether in water and bacteriochlorophyll a gradually begins to precipitate. The suspension is allowed to settle and then filtered. Received bacteriochlorophyll a raw, dissolved in chloroform (20 MT. The operation periselene repeat several times until, while spectral characteristics and TLC did not confirm the homogeneity of the compounds. The yield of the target product is from 1.2 to 1.5 g per 1 kg of biomass.

Distinctive features of the proposed method are:

1) the replacement of methanol in dioxane for the extraction of bacteriochlorophyll and biomass of purple bacteria,

2) deposition of bacteriochlorophyll that allows you to significantly speed up the purification of the target product,

3) non-chromatographic methods of purification, leading to significant oxidation of bacteriochlorophyll.

Example 1. 500 g frozen biomass Rhodopseudomonas capsulata (20% of air-dry weight) fill in 1.1 l of dioxane, stirred after thawing, centrifuged for 10 min with a speed of 3000 rpm, decanted and placed in a two-liter separating funnel together with 0.5 l of petroleum ether (so Kip. 70 - 90oC). The mixture is shaken and allowed to settle. The upper layer is separated and shaken with 1 l of water for the partial extraction of dioxane and petroleum ether gradually precipitation of bacteriochlorophyll. The aqueous layer was drained, and the hydrocarbon layer was filtered under vacuum. The precipitate was dried, dissolved in 20 m is s resultant deposition rates repeat twice.

Yield 0.60 g

Electronic spectrum in chloroform, max(the ratio of intensities) : 367, 581, 778 nm (1: 0.30: 0.95).

H1NMR, (CDCl3) memorial plaques: 9.4, 8.52, 8.38, 6.44, 4.21, 4.10, 3.86, 3.66, 3.44. 3.33, 2.5, 1.58, 1.41.

Example 2. 300 g of previously frozen biomass Rhodopseudomonas capsulata (18% air-dry weight) thawed, pour 0.7 l of dioxane, are thoroughly mixed, centrifuged, and decanted. Meal fill in 0.1 l of dioxane, centrifuged, and decanted. The extracts are combined and placed in a two-liter separating funnel together with 0.3 l of petroleum ether. The mixture is shaken and allowed to settle. The bottom layer is separated and the upper poured 1 liter of water and shake. After settling the aqueous layer was drained, and the hydrocarbon layer was filtered under vacuum. The precipitate was washed with petroleum ether (2 x 50 ml), dried, dissolved in 15 ml of chloroform and bacteriochlorophyll periostat 150 ml of petroleum ether. The precipitate of bacteriochlorophyll filtered off, washed with 100 ml of cold petroleum ether and dried in a vacuum desiccator under vacuum over paraffin.

Yield 0.41 g

Example 3. 660 g of previously frozen and thawed biomass Rhodopseudomonas capsulata (22% and.with.in.) fill in 1.2 l of dioxane, wellnow funnel together with 0.5 l of petroleum ether. The mixture is shaken and allowed to settle. The bottom fraction is separated and the upper fraction poured 1 liter of water and shake. After settling the aqueous layer was drained, and the hydrocarbon layer was filtered under vacuum. The precipitate is dried, dissolve in 50 ml of chloroform, the solution is gradually added to 300 ml of petroleum ether. The precipitation of bacteriochlorophyll filtered off and dried.

Yield 1.05 g

Example 4. The method is carried out as in example 1, the extraction of dioxane and pereosazhdeniya of chloroform spend hexane.

Yield 0.62 g

Literature:

1. Berger, G.; Kleo, J.; Andrianambinintsoa, S.; Neumann, J. M; Leonhard, M.// Preparation and purification of chlorophylls, bacteriochlorophylls and of their derivatives. // J. Liq. Chromatogr., 13(2), 333-44, 1990.5

The method of producing bacteriochlorophyll by destroying the cell walls of the biomass of purple bacteria, the extraction of natural pigment with an organic solvent and purification of the target product, characterized in that the extraction bacteriochlorophyll and are dioxane, followed by transfer of the pigment in petroleum ether and the separation of the target product with reduced levels of dioxane in petroleum ether, and purification of the target product is carried out by the resultant deposition rates of bacteriochlorophyll and chlorine

 

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