Novel route for clindamycin phosphate compounds

A technology of clindamycin phosphate and clindamycin, which is applied in organic compound/hydride/coordination complex catalysts, chemical/physical processes, sugar derivatives, etc., and can solve the problem that related substances do not meet the requirements of pharmacopoeia standards , high production costs, expensive and other issues

Inactive Publication Date: 2010-05-12
HAINAN LINGKANG PHARMA CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In the synthesis process of clindamycin phosphate reported in the literature, the 3 and 4 hydroxyl groups are usually protected by the method of forming arylene and propylene groups. However, because the arylene group is difficult to remove, it is not used in production Propylene protection has the advantages of easy operation, mild deprotection conditions, and low cost, and is widely used in production. However, because the latter is a reversible reaction, the reaction is incomplete and the related substances in the final product are too high and do not meet the Pharmacopoeia Standard requirements. At the same tim

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  • Novel route for clindamycin phosphate compounds
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  • Novel route for clindamycin phosphate compounds

Examples

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Embodiment 1

[0033] Embodiment 1 3, the synthesis of 4-oxo-isopropylidene clindamycin

[0034] The clindamycin of 100 grams (0.24mol) is joined in the acetone of 1500ml, then add 35 grams (0.26mol) zinc chloride powder, stir and react at room temperature for 12 hours, most of acetone is recovered by distillation under reduced pressure, then add 5 500ml of sodium bicarbonate solution and 500ml of ether, stirred, allowed to stand, layered, the organic phase was washed with 300ml of distilled water, then dried with anhydrous sodium sulfate, distilled under reduced pressure to obtain viscous, recrystallized with ethyl acetate , 99.2 g of the product was obtained, the yield was 89%, and the purity was 99.9%.

Embodiment 2

[0035] Example 2 Synthesis of 3,4-oxo-isopropylidene clindamycin phosphate

[0036] 50 grams (0.11mol) of 3,4-oxo-isopropylidene clindamycin was added to 300ml of carbon tetrachloride, nitrogen protection was introduced, and then N,N-diisopropylethylamine 100ml was added and N, N-dimethylaminopyridine 5 grams, the mixture was cooled to 0 ° C, slowly added dropwise 23 grams of phosphorus oxychloride, to maintain the reaction temperature is not more than 5 ° C, then reacted at 0 ° C for 1 hour, standing, The layers were separated, and the organic phase was washed with 200 ml of water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure at 50°C to obtain 54.5 g of the product, with a yield of 92% and a purity of 99.7%.

Embodiment 3

[0037] Example 3 Synthesis of Clindamycin Phosphate

[0038] Add 40 grams of 3,4-oxo-isopropylidene clindamycin phosphate into 200ml of acetic acid and 40ml of water, then heat to 85°C, react for 1.5 hours, then distill off most of the acetic acid under reduced pressure, and then add 100ml of water and 300ml of absolute ethanol were cooled to 5°C, stirred, and solids were precipitated, filtered, washed with ethanol, and dried at 60°C to obtain 33.3 g of the product, with a yield of 90%, a purity of 99.7%, and Mp: 209°C.

[0039] Elemental Analysis C 18 h 34 ClN2 o 8 PS molecular weight: 504.97

[0040] Theoretical value C: 42.8%, H: 6.8%, N: 5.5%, O: 25.4%, P: 6.1%, Cl: 7.0%, S: 6.4%;

[0041] Found values ​​C: 42.7%, H: 6.9%, N: 5.6%, O: 25.3%, P: 6.0%, Cl: 7.2%, S: 6.3%

[0042] 1 HNMR (CD 3 OD) δ7.2-7.45 (5H, m, Ph-H), 5.47 (1H, d, CONH), 5.11 (2H, m, ArCH 2 O), 4.1-4.8 (5H, m, 50CH - ), 3.89 (1H, m, R-CHCl), 3.76 (2H, m, 2NCH - ), 2.2-2.5 (3H, m, N-CH 3 ), 2.18 ...

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Abstract

The invention provides a novel route for clindamycin phosphate compounds. In particular, clindamycin serving as an initial reaction raw material undergoes hydroxyl protection, phosphorylation and hydrolysis reaction to obtain the clindamycin phosphate compounds. In the new route, a specific catalyst is used and phosphorus oxychloride is used as a phosphorylating agent, so that compared with the prior art, the new route has the advantages of greatly lowering consumption of phosphorus oxychloride, lowering production cost and being more suitable for industrialization.

Description

technical field [0001] The invention relates to a new route of clindamycin phosphate compound, which belongs to the field of drug synthesis. Background technique [0002] Clindarnycin, whose chemical name is 7(s)-chloro-7-deoxylincomycin, has the same antibacterial mechanism and antibacterial spectrum as lincomycin, but the antibacterial effect can be increased by 4-8 times. Its outstanding effect on Gram-positive bacteria, especially anaerobic bacteria, is a major feature of this product. Clindamycin is well absorbed after oral administration in the form of hydrochloride, and the food in the stomach and duodenum does not affect its absorption; the plasma half-life is 2-5h, and most of it has been metabolized in the body, only about 10% is excreted from the urine Excretion; the plasma half-life is slightly prolonged in patients with renal insufficiency, but there is no need to adjust the dose, and no allergy test is required before use. It is effective for bacteria resistan...

Claims

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Application Information

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IPC IPC(8): C07H15/16C07H1/02B01J31/02
Inventor 杨明贵
Owner HAINAN LINGKANG PHARMA CO LTD
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