合成路线:1) The condensation of N,N'-di(benzyloxycarbonyl)actinamine (I) with the L-glucose nitrosodimer (II) in DMF gives the oxime adduct (III),which is cyclized by means of aqueous HCl yielding the hemiketal triacetate (IV).The treatment of (IV) with anhydrous KHCO3 in acetonitrile affords the enone acetate (V),which is deacetylated with K2HPO4 in methanol to give N,N'-di(benzyloxycarbonyl)dehydrospectinomycin (VI).The hydrogenation of (VI) with H2 over Pd/BaSO4 in pyridine - isopropanol yields free spectinomycin (VII),which is protected again with benzyloxycarbonyl chloride as usual to give N,N'-di(benzyloxycarbonyl)spectinomycin (VIII).The formylation of (VIII) with formic acid - acetic anhydride gives the 2,6-di-O-formyl derivative (IX),which by treatment with acetic anhydride and dimethylaminopyridine (DMAP) is converted into the enol acetate (X).The reaction of (X) with dibromodimethylhydantoin (DBMH) in refluxing CCl4 under visible light illumination affords the unsaturated ketone (XI),which is treated with dimethylformamide dimethyl acetal in hot DMF,yielding the dimethylaminovinylene compound (XII).
合成路线:Reduction of (XII) with sodium cyanoborohydride in methanolic HCl gives the 2-dimethylaminoethyl compound (XIII),which is treated with m-chloroperbenzoic acid in ethylacetate - Skellysolve B to afford the vinyl derivative (XIV).The reaction of (XIV) with ethylmagnesium bromide and CuBr2 in THF affords the protected propyl-dehydrospectinomycin (XV),which is hydrogenated with lithium tri-sec-butyl borohydride in THF to afford the propyl-spectinomycin (XVI).Finally,this compound is deprotected by hydrogenation with H2 over Pd/C in methanol.2) The silylation of the dimethylaminovinylene compound (XII) with trimethylsilylchloride and hexamethyldisilazane in THF gives the silylated compound (XVII),which is treated with ethylmagnesium bromide to yield the 1-butenyl derivative (XVIII).The elimination of the silyl groups of (XVIII) with HF in acetonitrile affords N,N'-di(benzyloxycarbonyl)tetradehydrotrospectomycin (XIX),which is then hydrogenated with H2 over Pd/BaSO4 as before.
参考文献标题:The synthesis of trospectomycin (6'-n-propylspectinomycin,U-63,366F)
文献作者:Cain,G.A.; White,D.R.
参考来源:Tetrahedron Lett 1989,30(12),1469-72
合成路线:1) The condensation of N,N'-di(benzyloxycarbonyl)actinamine (I) with the L-glucose nitrosodimer (II) in DMF gives the oxime adduct (III),which is cyclized by means of aqueous HCl yielding the hemiketal triacetate (IV).The treatment of (IV) with anhydrous KHCO3 in acetonitrile affords the enone acetate (V),which is deacetylated with K2HPO4 in methanol to give N,N'-di(benzyloxycarbonyl)dehydrospectinomycin (VI).The hydrogenation of (VI) with H2 over Pd/BaSO4 in pyridine - isopropanol yields free spectinomycin (VII),which is protected again with benzyloxycarbonyl chloride as usual to give N,N'-di(benzyloxycarbonyl)spectinomycin (VIII).The formylation of (VIII) with formic acid - acetic anhydride gives the 2,6-di-O-formyl derivative (IX),which by treatment with acetic anhydride and dimethylaminopyridine (DMAP) is converted into the enol acetate (X).The reaction of (X) with dibromodimethylhydantoin (DBMH) in refluxing CCl4 under visible light illumination affords the unsaturated ketone (XI),which is treated with dimethylformamide dimethyl acetal in hot DMF,yielding the dimethylaminovinylene compound (XII).
合成路线:Reduction of (XII) with sodium cyanoborohydride in methanolic HCl gives the 2-dimethylaminoethyl compound (XIII),which is treated with m-chloroperbenzoic acid in ethylacetate - Skellysolve B to afford the vinyl derivative (XIV).The reaction of (XIV) with ethylmagnesium bromide and CuBr2 in THF affords the protected propyl-dehydrospectinomycin (XV),which is hydrogenated with lithium tri-sec-butyl borohydride in THF to afford the propyl-spectinomycin (XVI).Finally,this compound is deprotected by hydrogenation with H2 over Pd/C in methanol.2) The silylation of the dimethylaminovinylene compound (XII) with trimethylsilylchloride and hexamethyldisilazane in THF gives the silylated compound (XVII),which is treated with ethylmagnesium bromide to yield the 1-butenyl derivative (XVIII).The elimination of the silyl groups of (XVIII) with HF in acetonitrile affords N,N'-di(benzyloxycarbonyl)tetradehydrotrospectomycin (XIX),which is then hydrogenated with H2 over Pd/BaSO4 as before.
参考文献标题:Trospectomycin Sulfate
文献作者:Castar,J.; Patoia,L.
参考来源:Drugs Fut 1991,16(4),323
合成路线:1) The condensation of N,N'-di(benzyloxycarbonyl)actinamine (I) with the L-glucose nitrosodimer (II) in DMF gives the oxime adduct (III),which is cyclized by means of aqueous HCl yielding the hemiketal triacetate (IV).The treatment of (IV) with anhydrous KHCO3 in acetonitrile affords the enone acetate (V),which is deacetylated with K2HPO4 in methanol to give N,N'-di(benzyloxycarbonyl)dehydrospectinomycin (VI).The hydrogenation of (VI) with H2 over Pd/BaSO4 in pyridine - isopropanol yields free spectinomycin (VII),which is protected again with benzyloxycarbonyl chloride as usual to give N,N'-di(benzyloxycarbonyl)spectinomycin (VIII).The formylation of (VIII) with formic acid - acetic anhydride gives the 2,6-di-O-formyl derivative (IX),which by treatment with acetic anhydride and dimethylaminopyridine (DMAP) is converted into the enol acetate (X).The reaction of (X) with dibromodimethylhydantoin (DBMH) in refluxing CCl4 under visible light illumination affords the unsaturated ketone (XI),which is treated with dimethylformamide dimethyl acetal in hot DMF,yielding the dimethylaminovinylene compound (XII).
合成路线:Reduction of (XII) with sodium cyanoborohydride in methanolic HCl gives the 2-dimethylaminoethyl compound (XIII),which is treated with m-chloroperbenzoic acid in ethylacetate - Skellysolve B to afford the vinyl derivative (XIV).The reaction of (XIV) with ethylmagnesium bromide and CuBr2 in THF affords the protected propyl-dehydrospectinomycin (XV),which is hydrogenated with lithium tri-sec-butyl borohydride in THF to afford the propyl-spectinomycin (XVI).Finally,this compound is deprotected by hydrogenation with H2 over Pd/C in methanol.2) The silylation of the dimethylaminovinylene compound (XII) with trimethylsilylchloride and hexamethyldisilazane in THF gives the silylated compound (XVII),which is treated with ethylmagnesium bromide to yield the 1-butenyl derivative (XVIII).The elimination of the silyl groups of (XVIII) with HF in acetonitrile affords N,N'-di(benzyloxycarbonyl)tetradehydrotrospectomycin (XIX),which is then hydrogenated with H2 over Pd/BaSO4 as before.
参考文献标题:Synthesis and in vitro antibacterial properties of alkylspectinomycin analogs
文献作者:White,D.R.; Maring,C.J.; Cain,G.A.
参考来源:J Antibiot 1983,36(3),339-42
合成路线:A new synthesis of trospectomycin has been published: The protection of the amino groups of spectinomycin (I) with benzyl chloroformate gives compound (II),which is treated with trimethylsilylchloride to protect the hydroxyl groups yielding the fully protected compound (III).The reaction of (III) with tert-butyl hydroperoxide makes free the oxo group affording compound (IV),which is converted into the enol ester (V) with allyl chloroformate and LiHMDS.The trans-allylation of (V) in THF by means of Pd under Tsujii conditions gives the protected 3-butenyl derivative (VI),which is finally deprotected and simultaneously hydrogenated with H2 over Pd/Al2O3 in methanol-acetic acid.
参考文献标题:Oxidation and alkylation of spectinomycin derivatives: Synthesis of trospectomycin from spectinomycin
文献作者:Herrinton,P.M.; Hartley,W.M.; Klotz,K.L.
参考来源:J Org Chem 1993,58(3),678
合成路线:1) The condensation of N,N'-di(benzyloxycarbonyl)actinamine (I) with the L-glucose nitrosodimer (II) in DMF gives the oxime adduct (III),which is cyclized by means of aqueous HCl yielding the hemiketal triacetate (IV).The treatment of (IV) with anhydrous KHCO3 in acetonitrile affords the enone acetate (V),which is deacetylated with K2HPO4 in methanol to give N,N'-di(benzyloxycarbonyl)dehydrospectinomycin (VI).The hydrogenation of (VI) with H2 over Pd/BaSO4 in pyridine - isopropanol yields free spectinomycin (VII),which is protected again with benzyloxycarbonyl chloride as usual to give N,N'-di(benzyloxycarbonyl)spectinomycin (VIII).The formylation of (VIII) with formic acid - acetic anhydride gives the 2,6-di-O-formyl derivative (IX),which by treatment with acetic anhydride and dimethylaminopyridine (DMAP) is converted into the enol acetate (X).The reaction of (X) with dibromodimethylhydantoin (DBMH) in refluxing CCl4 under visible light illumination affords the unsaturated ketone (XI),which is treated with dimethylformamide dimethyl acetal in hot DMF,yielding the dimethylaminovinylene compound (XII).
合成路线:Reduction of (XII) with sodium cyanoborohydride in methanolic HCl gives the 2-dimethylaminoethyl compound (XIII),which is treated with m-chloroperbenzoic acid in ethylacetate - Skellysolve B to afford the vinyl derivative (XIV).The reaction of (XIV) with ethylmagnesium bromide and CuBr2 in THF affords the protected propyl-dehydrospectinomycin (XV),which is hydrogenated with lithium tri-sec-butyl borohydride in THF to afford the propyl-spectinomycin (XVI).Finally,this compound is deprotected by hydrogenation with H2 over Pd/C in methanol.2) The silylation of the dimethylaminovinylene compound (XII) with trimethylsilylchloride and hexamethyldisilazane in THF gives the silylated compound (XVII),which is treated with ethylmagnesium bromide to yield the 1-butenyl derivative (XVIII).The elimination of the silyl groups of (XVIII) with HF in acetonitrile affords N,N'-di(benzyloxycarbonyl)tetradehydrotrospectomycin (XIX),which is then hydrogenated with H2 over Pd/BaSO4 as before.
参考文献标题:The stereospecific synthesis of spectinomycin
文献作者:White,D.R.; Mizsak,S.A.; Birkenmeyer,R.D.; Thomas,R.C.; Wiley,V.H.
参考来源:Tetrahedron Lett 1979,302737-40
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