149934-19-0Relevant academic research and scientific papers
An improved process for the preparation of Tigecycline intermediate and process for the preparation of Tigecycline therefrom
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, (2022/02/15)
The present invention relates to a process for the preparation of Tigecycline intermediate i.e. 9-amino minocycline of formula-1(C). More particularly, the present invention relates to a process for the preparation of 9-amino minocycline of formula 1(C) and a process for the preparation of Tigecycline of formula 1 from 9-nitro minocycline of formula 1(B).
Synthetic method of minocycline and derivative of minocycline
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Paragraph 0022; 0023, (2019/09/13)
The invention relates to a synthetic method of minocycline and substituted minocycline, and especially synthesis of 9-amino minocycline. 9-amino minocycline is an important intermediate of tigecycline, and tigecycline is mostly used for control on multiple resistant bacteria. The raw materials are easily available; the synthetic route is short; reaction conditions are mild; the yield is high; thetechnology is simple; and the synthetic method is suitable for large scale production.
NITRATION OF TETRACYCLINES
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Page/Page column 27-28, (2010/11/03)
The invention in one embodiment is directed to a method of preparing a compound of formula (1), or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently chosen from hydrogen, (C1-C6)alkyl, and cycloalkyl, R is -NR3R4, where R3 and R4 are each independently chosen from hydrogen, and (C1-C4)alkyl; and n ranges from 1-4, comprising: (a) reacting a C1-C12 alkyl nitrate with a compound of formula (2), or a salt thereof, in the presence of an acid at a concentration greater than 70% weight of acid / weight of solution, the acid being selected from the group consisting of sulfuric acid, and R5-SO3H wherein R5 is C1-C4 alkyl optionally substituted with one or more halogen, or R5 is C6-C10 aryl optionally substituted with one or more C1-C4 alkyl or halogen, to produce a reaction mixture containing a compound of formula (3) or a salt thereof; (b) reducing the compound of formula (3) or a salt thereof to form a compound of formula (4) or a salt thereof; (c) acylating the compound of formula (4) to form a compound of formula (1), and (d) optionally forming a pharmaceutically acceptable salt of the compound of formula (1).
Minocycline-based europium(III) chelate complexes: Synthesis, luminescent properties, and labeling to streptavidin
Nishioka, Takuya,Yamamoto, Yuji,Hashino, Kimikazu,Matsumoto, Kazuko
experimental part, p. 2357 - 2374 (2010/03/30)
Two chelate ligands for europium(III) having minocycline (=(4S,4aS,5aR,12aS)-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10, 12,12a-tetrahydroxy-1,11-dioxonaphthacene-2-carboxamide; 5) as a VIS-light-absorbing group were synthesized as possible VIS-light-excitable stable Eu3+ complexes for protein labeling. The 9-amino derivative 7 of minocycline was treated with H6TTHA (= triethylenetetraminehexaacetic acid=3,6,9,12-tetrakis(carboxymethyl)-3,6,9,12- tetraazatetradecanedioic acid) or H5DTPA (= diethylenetriaminepentaacetic acid=N,N-bis{2-[bis(carboxymethyl)amino]ethyl} glycine) to link the polycarboxylic acids to minocycline. One of the Eu 3+ chelates, [Eu3+(minocycline-TTHA)] (13), is moderately luminescent in H2O by excitation at 395 nm, whereas [Eu 3+(minocycline-DTPA)] (9) was not luminescent by excitation at the same wavelength. The luminescence and the excitation spectra of [Eu 3+(minocycline-TTHA)] (13) showed that, different from other luminescent EuIII chelate complexes, the emission at 615 nm is caused via direct excitation of the Eu3+ ion, and the chelate ligand is not involved in the excitation of Eu3+. However, the ligand seems to act for the prevention of quenching of the Eu3+ emission by H2O. The fact that the excitation spectrum of [Eu3+(minocycline-TTHA)] is almost identical with the absorption spectrum of Eu3+ aqua ion supports such an excitation mechanism. The high stability of the complexes of [Eu3+(minocycline-DTPA)] (9) and [Eu3+(minocycline-TTHA)] (13) was confirmed by UV-absorption semi-quantitative titrations of H 4(minocycline-DTPA) (8) and H5(minocycline-TTHA) (12) with Eu 3+. The titrations suggested also that an 1:1 ligand Eu3+ complex is formed from 12, whereas an 1:2 complex was formed from 8 minocycline-DTPA. The H5(minocycline-TTHA) (12) was successfully conjugated to streptavidin (SA) (Scheme 5), and thus the applicability of the corresponding Eu3+ complex to label a protein was established.
TIGECYCLINE AND METHODS OF PREPARING INTERMEDIATES
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Page/Page column 11; 19, (2009/04/24)
Methods of preparing and purifying 9-nitrominocycline and 9-aminominocycline and salts thereof used in the process of making tigecycline, are disclosed. In one embodiment, the invention is directed to a method of preparing the compound of formula 1 or a pharmaceutically acceptable salt thereof, comprising: (a) reacting nitric acid with the compound of formula 2, or a salt thereof, to produce a reaction mixture comprising an intermediate; and (b) further reacting the intermediate to form the compound of formula 1, wherein the intermediate is isolated from the reaction mixture, the method further comprising sparging with an inert gas prior to step (a).
METHODS FOR REDUCING 7/9-NITROTETRACYCLINE DERIVATIVES
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Page/Page column 8, (2008/06/13)
The invention is directed to processes for the reduction of tetracycline intermediates having a NO2 group.
Synthesis and antibacterial activity of 9-substituted minocycline derivatives
Sum, Phaik-Eng,Ross, Adma T.,Petersen, Peter J.,Testa, Raymond T.
, p. 400 - 403 (2007/10/03)
A number of 9-acylamino and 9-sulfonylamino derivatives of minocycline have been synthesized for structure-activity relationship studies. These compounds showed activity against both tetracycline-susceptible and tetracycline-resistant strains. Many of the
