9-Amino minocycline hydrochloride

Name: 9-Amino minocycline hydrochloride
SKU: ACM149934214
Rating: 5 (1 reviews)

CAS

149934-21-4

Catalog Number

ACM149934214

Category

Main Products

Molecular Weight

508.95

Molecular Formula

C23H28N4O7·HCl

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Specification

Synonyms

9-Amino Minocycline HCl

Appearance

Yellow powder

9-Aminominocycline Hydrochloride for the Mannich Reaction of Minocycline

Chiwunze, Tirivashe E., et al. South African Journal of Chemistry, 2016, 69, 72-78.

This paper reported a mild synthetic route for the synthesis of novel minocycline derivatives using a proline-catalyzed three-component Mannich reaction. The reaction was optimized using 9-aminominocycline, hydroxyacetone, and nitrobenzaldehyde in a one-pot reaction.
· Synthesis of Mannich products from hydroxyacetone
To a suspension of L-proline (4.2 mg, 0.3 mmol) in methanol (2.0 mL), 9-amino minocycline hydrochloride (60 mg, 1.1 mmol) was added. Then the aldehyde (1.0 mmol) and the ketone (1.0 mL) were added to this mixture, and stirred overnight. The reactions were then purified straight using semi-preparative reverse-phase HPLC.
· Evaluation of antimicrobial activity
In vitro antimicrobial activity of the Mannich adducts against Gram-negative and Gram-positive bacteria was assessed. The Mannich adducts were more active against Gram-positive bacteria than against Gram-negative bacteria.

9-Aminominocycline Hydrochloride for the Preparation of 9-Heteroaryl-Substituted Minocycline Analogues

Liu, Jiuyu, et al. SSRN, 2024, 29.

A series of novel 9-heteroaryl-substituted minocycline analogs were designed and synthesized, which showed good in vitro activity against Mycobacterium tuberculosis and Mycobacterium abscessus, were stable in water for more than 7 days, avoided TetX inactivation in Mycobacterium abscessus, and were non-cytotoxic in HepG2 mammalian cells.
General method for synthesis of 9-substituted minocyclines
To make 9-substituted minocyclines, 9-amino minocycline hydrochloride (1 equivalent), the corresponding acid (1.2-2.0 equivalents), and HATU (1.2-2.0 equivalents) were dissolved in DMF. Into this mixture was added DIPEA (4.0 equivalents). The reaction was stirred at room temperature from 2 hours to overnight, and tracked by UPLC. After the reaction, the solvent was evaporated in vacuum and the remaining residue was purified by reverse-phase column chromatography (0-40% acetonitrile/water).
Structure-activity relationship of 9-aryl-substituted minocycline analogues
Research revealed that a methylene linker is ideal between the amide and the terminal cyclic group; analogues lacking a linker or featuring an ethylene linker exhibited reduced potency and susceptibility to TetX modification. Adding a heterocyclic side chain at the 9-position along with a methylene spacer significantly enhanced antimycobacterial activity compared to benzene analogues. Adjusting the nitrogen position in the pyridine ring resulted in three analogues, all demonstrating consistent activity against both Mtb and Mab. Bioisosteric substitution of the pyridine ring with thiazole and pyrazole preserved antimycobacterial activity, with thiazole 2e identified as the most potent analogue against Mab.