";s:4:"text";s:9018:" Its spectrum of activity includes a range of aerobic and anaerobic gram-positive and gram-negative microorganisms, and like other macrolides, clarithromycin is highly active against atypical pathogens such as M. pneumoniae.
Azithromycin pharmacokinetics permit a five-day, single daily dose regimen for respiratory tract and soft tissue infections, and a single 1 g dose of azithromycin effectively treats C trachomatis genital infections; these more convenient dosing schedules improve patient compliance. Unable to load your collection due to an error
Superior pharmacodynamic properties separate the new macrolides from the prototype, erythromycin. Data synthesis: Erythromycin, the first macrolide discovered, is metabolized by the cytochrome P450 enzyme system. 1992 Jul;44(1):117-64. doi: 10.2165/00003495-199244010-00009.Millán-Oñate J, Millan W, Mendoza LA, Sánchez CG, Fernandez-Suarez H, Bonilla-Aldana DK, Rodríguez-Morales AJ.Ann Clin Microbiol Antimicrob.
2015 Nov 12;10:29-37. doi: 10.4137/ACI.S31857. Clarithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms, resulting in inhibition of protein synthesis. This site needs JavaScript to work properly. It inhibits bacterial protein synthesis by binding to the bacterial 50S ribosomal subunit.
Drugs. ; Can also be strong acid weak base salt, general formula X Br, X be the weak base positively charged ion, for example ammonium, iron ion, zine ion etc.Catalyst levels is 0.01ï½0.4 molar equivalent of erythromycin oxime; Silanization catalyzed reaction temperature is 0ï½40 â; The silanization catalyzed reaction time is 1ï½10 hour.2, in the above-mentioned hydrobromate catalyzer, preferred pyridine hydrobromide.In the strong acid weak base salt catalyst, preferred brometo de amonio.3, preferred 0.18ï½0.4 molar equivalent of catalyst levels.4, silanization catalyzed reaction temperature is preferred 20ï½30 â.5, preferred 2ï½3h of silanization catalyzed reaction time.The present invention uses an acidic catalyst catalysis Silanization reaction, accelerates Silanization reaction speed, and the reaction times shortens dramatically, and is shortened in the 3h by 8ï½10h of former technology; And reduced the usage quantity of the two silazane of hexamethyl; Process stabilizing, molar yield is brought up to more than 90% by 80% of former technology; Reduce by product, the impurity of silanization is not reduced in 1% by 10% of former technology, and the reaction conditions gentleness is easy to control; Aftertreatment is easy, and the three wastes are few; Production cost is low, is more suitable for suitability for industrialized production.Clearer in order to set forth, preparation process is not added catalyzer among the embodiment one, and embodiment two to embodiment nine has the interpolation catalyzer, forms contrast.Step 1: in 500 milliliters of four-hole reaction flasks of agitator, thermometer are housed, add 20.0 gram (0.0267mol) erythromycin A-9 oximes, the 200ml methylene dichloride, stirring adds 5.6 gram (0.0487mol) pyridine hydrochlorides and 5.3 gram (0.0616mol) 2-ethoxy propylenes down, and 20-25 â was reacted 15 minutes.Step 2: connect step 1, add the two silazane of 5.7 gram (0.0354mol) hexamethyl, 20ï½30 â were reacted 3 hours down.After reaction finishes, add 60 ml waters and stop, transfer pH to 9ï½10 with 20% sodium hydroxide solution again, wash with 60 milliliters of saturated brines, 60 ml waters successively, the underpressure distillation condensing crystal gets 26.6 and restrains, content 75.8%, wherein silanization content 11.6% not.Acetone refining gets elaboration 21.2 grams, content 92.6%, and molar yield reaches 81.1%.Step 2: connect step 1, add 5.7 and restrain the two silazane of (0.0354mol) hexamethyl, react adding 0.8 gram (0.005mol) pyridine hydrobromide after 5 minutes, 20ï½30 â were reacted 2 hours down.After reaction finishes, add 60 ml waters and stop, transfer PH to 9ï½10 with sodium hydroxide solution again, successively with 60 milliliters of saturated brines, the washing of 60 ml waters, the underpressure distillation condensing crystal gets 28.9 grams again, and main content is 86.3%, and silanization impurity is not 0.7%.Acetone refining gets elaboration 24.9 grams, content 96.0%, and molar yield reaches 95.5%.Step 2: connect step 1, add 5.7 and restrain the two silazane of (0.0354mol) hexamethyl, react adding 0.04 gram (0.00027mol) pyridine hydrobromide after 5 minutes, 20ï½30 â were reacted 10 hours down.After reaction finishes, add 60 ml waters and stop, transfer PH to 9ï½10 with sodium hydroxide solution again, successively with 60 milliliters of saturated brines, the washing of 60 ml waters, the underpressure distillation condensing crystal gets 27.7 grams again, and main content is 84.3%, and silanization impurity is not 2.9%.Acetone refining gets elaboration 23.6 grams, content 95.4%, and molar yield reaches 90.4%.Step 2: connect step 1, add 5.7 and restrain the two silazane of (0.0354mol) hexamethyl, react adding 1.7 gram (0.011mol) pyridine hydrobromides after 5 minutes, 20ï½30 â were reacted 1 hour down.After reaction finishes, add 60 ml waters and stop, transfer PH to 9ï½10 with sodium hydroxide solution again, successively with 60 milliliters of saturated brines, the washing of 60 ml waters, the underpressure distillation condensing crystal gets 27.2 grams again, and main content is 87.4%, and silanization impurity is not 0.1%.Acetone refining gets elaboration 24.4 grams, content 95.1%, and molar yield reaches 93.8%.Step 2: connect step 1, add 5.7 and restrain the two silazane of (0.0354mol) hexamethyl, react adding 1.7 gram (0.011mol) pyridine hydrobromides after 5 minutes, 0ï½10 â was reacted 5 hours down.After reaction finishes, add 60 ml waters and stop, transfer PH to 9ï½10 with sodium hydroxide solution again, successively with 60 milliliters of saturated brines, the washing of 60 ml waters, the underpressure distillation condensing crystal gets 27.9 grams again, and main content is 86.1%, and silanization impurity is not 1.2%.Acetone refining gets elaboration 24.3 grams, content 95.5%, and molar yield reaches 93.5%.Step 2: connect step 1, add 5.7 and restrain the two silazane of (0.0354mol) hexamethyl, react adding 0.8 gram (0.005mol) pyridine hydrobromide after 5 minutes, 30ï½40 â were reacted 2 hours down.After reaction finishes, add 60 ml waters and stop, transfer PH to 9ï½10 with sodium hydroxide solution again, successively with 60 milliliters of saturated brines, the washing of 60 ml waters, the underpressure distillation condensing crystal gets 27.0 grams again, and main content is 86.5%, and silanization impurity is not 0.1%.Acetone refining gets elaboration 23.8 grams, content 94.6%, and molar yield reaches 91.5%.Step 2: connect step 1, add 5.7 and restrain the two silazane of (0.0354mol) hexamethyl, react adding 0.6 gram (0.0061mol) brometo de amonio after 5 minutes, 20ï½30 â were reacted 6 hours down.After reaction finishes, add 60 ml waters and stop, transfer PH to 9ï½10 with sodium hydroxide solution again, successively with 60 milliliters of saturated brines, the washing of 60 ml waters, the underpressure distillation condensing crystal gets 27.2 grams again, and content is 83.0%, and the silanization foreign matter content is not 4.2%:.Acetone refining gets elaboration 23.3 grams, content 93.6%, and molar yield reaches 89.6%.Step 2: connect step 1, add 5.7 and restrain the two silazane of (0.0354mol) hexamethyl, react adding 1.0 gram (0.009mol) brometo de amonios after 5 minutes, 20ï½30 â were reacted 3 hours down.After reaction finishes, add 60 ml waters and stop, transfer PH to 9ï½10 with sodium hydroxide solution again, successively with 60 milliliters of saturated brines, the washing of 60 ml waters, the underpressure distillation condensing crystal gets 26.8 grams again, and content is 85.9%, and the silanization foreign matter content is not: 1.6%.Acetone refining gets elaboration 23.7 grams, content 94.2%, and molar yield reaches 90.6%.Step 2: connect step 1, add 5.7 and restrain the two silazane of (0.0354mol) hexamethyl, react adding 1.0 gram (0.009mol) brometo de amonios after 5 minutes, 30ï½40 â were reacted 3 hours down.After reaction finishes, add 60 ml waters and stop, transfer PH to 9ï½10 with sodium hydroxide solution again, successively with 60 milliliters of saturated brines, the washing of 60 ml waters, the underpressure distillation condensing crystal gets 26.3 grams again, and content is 86.3%, and the silanization foreign matter content is not: 1.2%.Acetone refining gets elaboration 23.4 grams, content 93.9%, and molar yield reaches 90.0%.The invention mainly discloses a method of silanization reaction during synthesizing clarithromycin.