药物Omadacycline（奥马环素）合成检索总结报告
一、Omadacycline（奥马环素）简介
Omadacycline（奥马环素）是由ParatekPharms公司研发，并于2024年10月在美国上市，主要用于由肺炎链球菌、金黄色葡萄球菌(甲氧西林敏感菌株)、流感嗜血杆菌、副流感嗜血杆菌、肺炎克雷伯菌、嗜肺军团菌、肺炎支原体和肺炎衣原体引起的社区获得性细菌性肺炎(CABP)成人患者的治疗。Omadacycline（奥马环素）作用机制是与细菌30S核糖体亚基结合并阻断其蛋白质合成。
Omadacycline（奥马环素）不良反应：恶心，呕吐，输液部位反应，丙氨酸氨基转移酶升高，门冬氨酸氨基转移酶升高，高血压，头痛，腹泻，失眠和便秘。
Omadacycline（奥马环素）分子结构式如下：
CAS:389139-89-3英文名称：Omadacycline中文名称：奥马环素
CAS：1075240-43-5英文名称：Omadacyclinetosylate中文名称：奥马环素对甲苯磺酸盐
二、Omadacycline（奥马环素）合成路线
1三、Omadacycline（奥马环素）合成路线一检索总结报告(一)Omadacycline（奥马环素）中间体2的合成方法一
合成方法合成方法一
实验步骤
Thecrude7-aminosancycline1wasdissolvedinmethanol.Tothissolution,formaldehydeand5%Pd/Cwereadded.Thereactionmixturewassubjectedtohydrogenationwithdeuteratedgas.Afterthecompletionofthereaction,thecrudematerialwasextractedbydichloromethaneatpH2andthenextractedatpH7.TheorganicextractsatpH7werecombinedandthesolventwasremoved.Theresidue2wasdissolvedin1NHClandpurifiedbyprep.HPLC(5g)
参考文献US2010/305072;(2010);(A1)English
(二)Omadacycline（奥马环素）中间体2的合成方法二
合成方法
实验步骤
1partbyweightof7-iodosancycline3,10partsbyweightofN,N-dimethylformamide,0.01partsbyweightofbistriphe-nylphosphinedichloride,Stiranddissolveat50°C,Add0.3
2参考文献
合成方法一
partsbyweightofdimethylaminetrimethyltinAnd0.5partsbyweightoftriethylamine,Thereactionisstirredfor6hours.Theendpointofthereactionis:thereactionliquidisdetectedbyHPLC.Thereactionwasterminatedwhenthecontentof7-iodostanninewaslessthan2%.Thereactionsolutionwaspassedthroughaseparationcolumncontaining20partsbyweightofamacroporousadsorptionresinin2hours,andthenelutedwith20partsbyweightofwaterand40partsbyweightofa20%aqueousmethanolsolutioninorder,10partsbyweight.Thefractionswereelutedwith80%methanol,andtheeluatecontainingthetargetfractionswascollected.TheeluatewasconcentratedunderreducedpressureandthepHofthereactionsolutionwasadjustedto1.0withconcentratedhydrochloricacid.Then,thereactionmixturewasdecoloredwithactivatedcarbonandthepHofthereactionliquidwasadjustedwithammonia.To3.8,freezecrystallization,filtercakeafterdrying,thatis,minocyclinehydrochloride.
CN106831479;(2017);(A)Chinese
(三)Omadacycline（奥马环素）中间体5的合成
合成方法
合成方法一
实验步骤
Chloroaceticanhydride(9.0g,53.01mmol),triazinane(5.0g,16.67mmol),anddichloromethane(10mL)werecombinedwithcoolinginanicebath.Thesolutionwasheatedat35oCfor20min,thencooledto20oC.Ina
separateflask,minocyclinehydrochloride2(5g,10mmol)wasslowlyaddedtotriflicacid(50mL)withcoolingwhilemaintainingat<35oC.TheacyliminiumprecursorsolutionwasslowlyaddedtominocyclineHCl/TfOHsolution
keepingat<40oC.Themixturewasheatedat35–40oCfor24h,thenquenchedinto10–15oCwater(200mL)over20minat<25oC.Tothismixturewasaddeddichloromethane(150mL)andadjustedtopH6.5with29%NH4OH(about50mL).Thelayerswereseparated,andtheaqueousphasewasextractedwithdichloromethane(3×25mL).The
combinedorganiclayerswereextractedwith15oC3NHCl(160mL).Thelayerswereseparatedandtheorganicphasewasre-extractedwith3NHCl(1×20mL,1×10mL).Thecombinedaqueouslayerswereassayedtocontain73–83%
3参考文献
TetrahedronLetters;vol.49;nb.42;(2008);p.6095–6100.
药物Omadacycline(奥马环素)合成检索总结报告
