10597-92-9Relevant articles and documents
Stereoselective Hydrogenation of Methacycline to Doxycycline Catalysed by Rhodium-Carborane Complexes
Pirotte, B.,Felekidis, A.,Fontaine, M.,Demonceau, A.,Noels, A. F.,et al.
, p. 1471 - 1474 (1993)
Doxycycline (2), a tetracycline antibiotic extensively used in chemotherapy, was obtained stereoselectively from the hydrogenation of methacycline (1), catalysed by novel rhodium-carborane complexes. Key words: stereoselective hydrogenation; rhodium; carborane; methacycline; doxycycline
Preparation method of doxycycline hydrochloride intermediate hydride
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Paragraph 0026; 0029; 0031; 0034, (2017/07/19)
The invention discloses a preparation method of a doxycycline hydrochloride intermediate hydride. The preparation method comprises adding dried oxytetracycline chloride into a dehydration pot containing HF, carrying out reaction dehydration, carrying out standing, evaporating and concentrating to remove HF, collecting the concentrated solution through methanol, neutralizing the methanol solution containing the concentrated solution through calcium hydroxide or calcium oxide powder, carrying out a hydrogenation reaction process on the neutralized methanol solution in the presence of a Pd/C catalyst and an inhibitor, filtering the reaction product, and carrying out a salt formation reaction process on the filtrate and a sulfonyl salicylate methanol solution to obtain the doxycycline hydrochloride intermediate hydride. The preparation method is free of p-toluenesulfonic acid, has simple processes, can be operated easily and greatly reduces a production cost.
Solid state chemistry of the antibiotic doxycycline: Structure of the neutral monohydrate and insights into its poor water solubility
Legendre, Alexandre O.,Silva, Laila R. R.,Silva, Douglas M.,Rosa, Iara M. L.,Azarias, Lilian C.,De Abreu, Polyana J.,De Araujo, Magali B.,Neves, Person P.,Torres, Claudia,Martins, Felipe T.,Doriguetto, Antonio C.
experimental part, p. 2532 - 2540 (2012/07/28)
The active pharmaceutical ingredient (API) doxycycline (DOX) is a broad-spectrum antibiotic mainly used in the treatment of respiratory and urinary tract infections and, like many drugs, its efficacy may be affected by the crystal form. Up to now, only the crystal structure of doxycycline hyclate (DOX·HYC) (generic name of brand names such as DORYX, PERIOSTAT, ATRIDOX, and VIBRAMYCIN) has been reported. This study presents the single-crystal X-ray diffractometry structural characterisation of another crystal form, doxycycline monohydrate (DOX·H2O) (generic name of brand names such as MONODOX and ORACEA). The DOX·H2O structure was compared with the known DOX·HYC one in terms of intra- and intermolecular geometries, and their melting temperature, water solubility and dissolution rate were measured. These data allowed us to establish relationships between solid state properties related to the pharmaceutical performance of the two DOX crystal variants and their supramolecular structures for the first time. Both hyclate and monohydrate forms crystallise the DOX molecules as zwitterions in which their dimethylamine groups are protonated and one of their hydroxyl groups is deprotonated. Whereas two conformers were observed in the DOX·HYC (i.e., the amine group is next to the enolate in one of them (T1) and beside the carbonyl in the other one (T2)), only one (T2) was found in DOX·H2O. Additionally, in the hyclate form, the presence of ethanol in the crystal lattice could be related to a rotation around the C-C bond of the amide group, directing the oxygen toward the amine group in one (T1) of the two conformers present in this solid state phase. Meanwhile, in the other crystallographically independent molecule (T2), the amide nitrogen is on the same side as the amine. However, only the conformer similar to T1 in DOX·HYC was observed in DOX·H2O. The crystal packing of DOX·H2O was stabilised by several intermolecular hydrogen bonds, with each drug entity interacting with another two DOX and three water molecules in such a way that a compact supramolecular network was formed. This structure was saturated in terms of hydrogen bonding, which could be related to its lower solubility and dissolution rate relative to DOX·HYC. The Royal Society of Chemistry 2012.
SYNTHESIS OF TETRACYCLINES AND ANALOGUES THEREOF
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Page/Page column 117-118, (2008/06/13)
The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The modular synthesis of tetracyclines and tetracycline analogs described provides an efficient and enantioselective route to a variety of tetracycline analogs and polycyclines previously inaccessible via earlier tetracycline syntheses and semi-synthetic methods. These analogs may be used as anti-microbial agents or anti-proliferative agents in the treatment of diseases of humans or other animals.
Preparation and characterization of 4-epidoxycycline
Kertscher,Habermann,Pohle,Tauchert,Hennig,Eger
, p. 287 - 296 (2007/10/03)
4-Epidoxycycline was prepared from commercial doxycycline. The isolation of 4-epidoxycycline was achieved by preparative column chromatography on silica gel. Structures were confirmed with thin layer chromatography and NMR spectroscopy. The antibacterial activity of 4-epidoxycycline in vitro was evaluated.
Ligand effects in the hydrogenation of methacycline to doxycycline and epi-doxycycline catalysed by rhodium complexes molecular structure of the key catalyst [closo-3,3-(η2,3-c7h7ch2)-3,1,2-rhc2b9h11]
Felekidis,Goblet-Stachow,Liegeois,Pirotte,Delarge,Demonceau,Fontaine,Noels,Chizhevsky,Zinevich,Bregadze,Dolgushin,Yanovsky,Struchkov
, p. 405 - 412 (2007/10/03)
The catalytic reduction of the exocyclic methylene group of methacycline (A) leads to the formation of two diastereoisomers, doxycycline (B, the α-epimer) and 6-epi-doxycycline (C, the β-epimer), with a selectivity which markedly depends on the nature of hydrocarbon and carborane ligands of closo-(π-cyclodienyl)rhodacarborane catalysts. Neutral norbornadienyl complexes with unsubstituted carborane ligands [closo-3,3-(η2,3-C7H7CH2)-3,1,2-RhC2B9H11] (1) and [closo-2,2-(η2,3-C7H7CH2)-2,1,7-RhC2B9H11] (7) are more active and afford higher selectivity in the formation of doxycycline than those having mono-or di-substituents at the carborane cage, [closo-3,3-(cyclodienyl)-1-R-2-R′-3,1,2-RhC2B9H9] (R = H, R′ = Me, PhCH2; R = R′ = Me; cyclodienyl = η2,3-C7H7CH2 or η-C10H13) as well as those from the closely related series of η5-cyclopentadienyl complexes [(η2,3-C7H7CH2)Rh(η5-C5Rn)]+PF-6 (Rn = H5, Me5, or H2-1,2,4-Ph3). Mechanistic aspects of the hydrogenation reaction of methacycline are sketched. The results of the X-ray diffraction study of the best catalyst 1 are reported.
