合成路线:Halogenation of allylamine (I) with either bromine or sulfuryl chloride produced the corresponding (halomethyl)aziridines (II).Subsequent treatment of (II) with n-butyllithium at -78 C yielded 1-azabicyclobutane (III).Opening of the bicyclic system of (III) with formic acid followed by acid hydrolysis provided 3-hydroxyazetidine (IV).This was condensed with 2-(methylsulfanyl)thiazoline (V) to give thiazolinylazetidine (VI).Alternatively,3-hydroxyazetidine (IV) was condensed with 2-chloroethyl isothiocyanate (VII) to give the intermediate thiourea (VIII),which cyclized to the thiazoline (VI).Conversion of the hydroxyl group of (VI) into the thioacetate (IX) was carried out by either coupling with thioacetic acid under Mitsunobu conditions or by conversion to mesylate (X) followed by displacement with potassium thioacetate.The required thiol (XI) was then obtained from (IX) by basic hydrolysis of the thioacetate ester.
合成路线:Condensation of (phosphoryloxy)carbapenem (XVI) with 3-mercapto-1-(1,3-thiazolin-2-yl)azetidine (XI) gave thioether (XVII).The p-nitrobenzyl ester group of (XVII) was then deprotected with Zn powder to afford the target carboxylic acid.
合成路线:Halogenation of allylamine (I) with either bromine or sulfuryl chloride produced the corresponding (halomethyl)aziridines (II).Subsequent treatment of (II) with n-butyllithium at -78 C yielded 1-azabicyclobutane (III).Opening of the bicyclic system of (III) with formic acid followed by acid hydrolysis provided 3-hydroxyazetidine (IV).This was condensed with 2-(methylsulfanyl)thiazoline (V) to give thiazolinylazetidine (VI).Alternatively,3-hydroxyazetidine (IV) was condensed with 2-chloroethyl isothiocyanate (VII) to give the intermediate thiourea (VIII),which cyclized to the thiazoline (VI).Conversion of the hydroxyl group of (VI) into the thioacetate (IX) was carried out by either coupling with thioacetic acid under Mitsunobu conditions or by conversion to mesylate (X) followed by displacement with potassium thioacetate.The required thiol (XI) was then obtained from (IX) by basic hydrolysis of the thioacetate ester.
合成路线:Condensation of (phosphoryloxy)carbapenem (XVI) with 3-mercapto-1-(1,3-thiazolin-2-yl)azetidine (XI) gave thioether (XVII).The p-nitrobenzyl ester group of (XVII) was then deprotected with Zn powder to afford carboxylic acid.Finally,treatment of (XVIII) with either iodo or chloromethyl pivalate (XIX) produced the target compound.
参考文献标题:Carbapenem-3-carboxylic acid ester derivs.
文献作者:Abe,T.; Kumagai,T.(Lederle (Japan),Ltd.)
参考来源:EP 0808315; JP 1999504039; US 5886172; WO 9721712
合成路线:Halogenation of allylamine (I) with either bromine or sulfuryl chloride produced the corresponding (halomethyl)aziridines (II).Subsequent treatment of (II) with n-butyllithium at -78 C yielded 1-azabicyclobutane (III).Opening of the bicyclic system of (III) with formic acid followed by acid hydrolysis provided 3-hydroxyazetidine (IV).This was condensed with 2-(methylsulfanyl)thiazoline (V) to give thiazolinylazetidine (VI).Alternatively,3-hydroxyazetidine (IV) was condensed with 2-chloroethyl isothiocyanate (VII) to give the intermediate thiourea (VIII),which cyclized to the thiazoline (VI).Conversion of the hydroxyl group of (VI) into the thioacetate (IX) was carried out by either coupling with thioacetic acid under Mitsunobu conditions or by conversion to mesylate (X) followed by displacement with potassium thioacetate.The required thiol (XI) was then obtained from (IX) by basic hydrolysis of the thioacetate ester.
合成路线:Condensation of (phosphoryloxy)carbapenem (XVI) with 3-mercapto-1-(1,3-thiazolin-2-yl)azetidine (XI) gave thioether (XVII).The p-nitrobenzyl ester group of (XVII) was then deprotected with Zn powder to afford the target carboxylic acid.
合成路线:Halogenation of allylamine (I) with either bromine or sulfuryl chloride produced the corresponding (halomethyl)aziridines (II).Subsequent treatment of (II) with n-butyllithium at -78 C yielded 1-azabicyclobutane (III).Opening of the bicyclic system of (III) with formic acid followed by acid hydrolysis provided 3-hydroxyazetidine (IV).This was condensed with 2-(methylsulfanyl)thiazoline (V) to give thiazolinylazetidine (VI).Alternatively,3-hydroxyazetidine (IV) was condensed with 2-chloroethyl isothiocyanate (VII) to give the intermediate thiourea (VIII),which cyclized to the thiazoline (VI).Conversion of the hydroxyl group of (VI) into the thioacetate (IX) was carried out by either coupling with thioacetic acid under Mitsunobu conditions or by conversion to mesylate (X) followed by displacement with potassium thioacetate.The required thiol (XI) was then obtained from (IX) by basic hydrolysis of the thioacetate ester.
合成路线:Condensation of (phosphoryloxy)carbapenem (XVI) with 3-mercapto-1-(1,3-thiazolin-2-yl)azetidine (XI) gave thioether (XVII).The p-nitrobenzyl ester group of (XVII) was then deprotected with Zn powder to afford carboxylic acid.Finally,treatment of (XVIII) with either iodo or chloromethyl pivalate (XIX) produced the target compound.
参考文献标题:L-084,a new oral carbapenem: Synthesis and structure-activity relationships of C2-substituted 1beta-methylcarbapenems
文献作者:Satoh,C.; Mihira,A.; Yamamoto,S.; Hayashi,K.; Kitamura,M.; Tamai,S.; Abe,T.; Kumagai,T.; Hikida,M.
参考来源:38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998,San Diego) 1998,Abst F-64
产品链接: CAS No. 161715-21-5››