ChemicalBook CAS DataBase List Minocycline

Minocycline synthesis

5synthesis methods

Product Name:Minocycline
CAS Number:10118-90-8
Molecular formula:C23H27N3O7
Molecular Weight:457.48

Minocycline, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12 a-octahydro- 3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacencarboxamide (32.3.17), is synthesized from 6-dimethyl-tetracycline (32.3.11), which is synthesized as a result of the vital activity of S. aureofaciens, in which the mechanism of transferring methyl groups is disrupted, or from a common strain of the same microorganisms, but with the addition of compounds such as ethionin, D-norleucine or D-methionine to the medium for developing this actinomycete, which are antimetabolytes of methionine, the primary donor of methyl groups in microbiological synthesis of tetracycline molecules. Hydrogenolysis of the aforementioned 6-demethyltetracycline (32.3.11) with hydrogen using a palladium on carbon catalyst gives 4-dimethylamino-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo- 2-napthacencarboxamide (32.3.12), which is nitrated at position 9 by potassium nitrate in aqueous hydrofluoric acid, which forms the nitro compound (32.3.13). This is reduced to the corresponding amino derivative (32.3.14) by hydrogen over platinum dioxide. The resulting aminophenyl compound (32.3.14) is then nitrated with nitric acid in the presence of sulfuric acid to make 7-nitro-9-amino-4-naphthacencarboxamide (32.3.15).
This undergoes diazotization when reacted with butylnitrate in sulfuric acid, and the resulting diazo derivative (32.3.16) is reduced with hydrogen using a palladium on carbon catalyst. During this, the product is deazotized, while the nitro group is simultaneously reduced to an amino group, which undergoes exhaustive methylation by formaldehyde into minocycline (32.3.17).

Tigecycline Metabolite M6 (9-AniMoMinocycline)

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Yield:10118-90-8 85%

Reaction Conditions:

with nitrous acid isobutyl ester in N,N-dimethyl-formamide at 70; for 0.75 h;

Steps:

5 Example 5: Synthesis of minocycline
9-aminominocycline (15.0 mmol) was dissolved in 30 ml of N,N-dimethylformamide in a 500 ml three-necked flask. After heating to 66 ° C, isobutyl nitrite (5.94 g, 15.2 mmol) solution in 100 ml of N,N-dimethylformamide, about 15 minutes, then stir the reaction at 70 ° C for half an hour, cool, pour into 1.5 liters of water, extract with ethyl acetate, extract The extract was washed with 1N aqueous HCl and brine, dried and evaporated. The yield was 85%.

References:

Li Wei;Yang Anya;Yang Shangjin CN110156624, 2019, A Location in patent:Paragraph 0024; 0025

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13614-98-7 Synthesis