公开(公告)号：US06211348B1

公开(公告)日：2001-04-03

申请号：US09393322

申请日：1999-09-10

申请人： Amalija Narandja ,  Nevenka Lopotar ,  Zoran Mandić

发明人： Amalija Narandja ,  Nevenka Lopotar ,  Zoran Mandić

IPC分类号： C07H1708

CPC分类号： C07H17/08

摘要： The present invention relates to 12,13-dihydroxy derivatives of tylosin, new semisynthetic compounds of the macrolide class, and to a process for their preparation. According to the present invention by the oxidation of 13-hydroxy derivative a 12,13-dihydroxy compound is obtained, which can be subsequently subjected to a series of reactions such as oximation, reduction (catalytic, electrochemical) or hydrolysis yielding corresponding dihydro or tetrahydro 12,13-dihydroxy derivatives.

摘要翻译： 本发明涉及泰乐菌素的12,13-二羟基衍生物，大环内酯类的新的半合成化合物及其制备方法。 根据本发明，通过氧化13-羟基衍生物，得到12,13-二羟基化合物，其随后可进行一系列反应，如肟化，还原（催化，电化学）或水解，产生相应的二氢或四氢 12,13-二羟基衍生物。

公开(公告)号：US5688924A

公开(公告)日：1997-11-18

申请号：US696178

申请日：1996-08-13

申请人： Amalija Narandja ,  Nevenka Lopotar

发明人： Amalija Narandja ,  Nevenka Lopotar

IPC分类号： A61K31/70 ,  A61K31/7042 ,  A61K31/7048 ,  A61P31/04 ,  B01J23/42 ,  B01J23/44 ,  C07B61/00 ,  C07H17/08 ,  C07D313/00 ,  C07H5/06

CPC分类号： C07H17/08

摘要： The invention relates to derivatives of 12,13-epoxy-tylosin, the novel seynthetic antibiotics from tylosin group and the methods of their preparation. According to this invention hydrogenation followed by oximation of 12,13-epoxy-tylosin derivatives yields the following tylosin derivatives: 10,11-dihydro-12,13-epoxy, respectively 10,11-dihydro-12,13-epoxy oxime. Direct oximation of 12,13-epoxy tylosin derivative gives 12,13-epoxy oxime derivatives of tylosin.

摘要翻译： 本发明涉及12,13-环氧 - 泰乐菌素衍生物，泰乐菌素组合的新型半合成抗生素及其制备方法。 根据本发明，12,13-环氧 - 泰乐菌素衍生物的氢化反应产生以下泰乐菌素衍生物：10,11-二氢-12,13-环氧基，分别为10,11-二氢-12,13-环氧肟。 12,13-环氧泰乐菌素衍生物的直接肟化得到泰乐菌素的12,13-环氧肟衍生物。

公开(公告)号：US06504035B1

公开(公告)日：2003-01-07

申请号：US09959692

申请日：2002-01-28

申请人： Amalija Narandja ,  Nevenka Lopotar ,  Marko Djerek ,  Dra{haeck over (z)}en Pavlović

发明人： Amalija Narandja ,  Nevenka Lopotar ,  Marko Djerek ,  Dra{haeck over (z)}en Pavlović

IPC分类号： C07D32100

CPC分类号： C07H17/08

摘要： The present invention relates to derivatives of 3-deoxy desmycosin of the formula I, wherein, starting from triply protected desmycosin, there are performed an oxidation at C-3 in the first step and then, optionally, a hydrogenation of double bonds and an epoxidation followed by a reductive opening of the oxirane ring. The present invention also relates to derivatives of 3-deoxy-desmycosin of the formula II, wherein in the first step triacetyl desmycosin is hydrogenated and then, via an intermediate mesylate, it is converted to a 2,3-didehydro derivative; or 2,3-didehydro-desmycosin is subjected to epoxidation reactions followed by a reductive opening of the oxirane ring.

摘要翻译： 本发明涉及式I的3-脱氧去糖霉素衍生物，其中，从三重保护的脱沙霉素开始，在第一步中在C-3进行氧化，然后任选地进行双键氢化和环氧化 随后是环氧乙烷环的还原开口。 本发明还涉及式II的3-脱氧 - 去霉霉素的衍生物，其中在第一步中，将三乙酰基脱沙霉素氢化，然后经由甲磺酸中间体转化为2,3-二脱水衍生物; 或2,3-二脱氢脱硫霉素进行环氧化反应，然后进行环氧乙烷环的还原开口。

公开(公告)号：US5962661A

公开(公告)日：1999-10-05

申请号：US114514

申请日：1998-07-14

申请人： Nevenka Lopotar ,  Amalija Narandja ,  Zoran Mandic

发明人： Nevenka Lopotar ,  Amalija Narandja ,  Zoran Mandic

IPC分类号： C07H17/08 ,  A61K31/70 ,  C07H15/04 ,  C07H17/00 ,  C07H15/00

CPC分类号： C07H15/04 ,  C07H17/00

摘要： Seco compounds from a class of tylosins represented by the formula I whereinR stands for H or CH.sub.3,R.sup.1 stands for H, CH.sub.3, C.sub.1 -C.sub.3 acyl or aryl sulfonyl,R.sup.2 stands for H and R.sup.3 stands for NH.sub.2 or OH, or R.sup.2 and R.sup.3 together stand for .dbd.O or .dbd.NOH,R.sup.4 stands for H or C.sub.1 -C.sub.3 acyl,and the line - - - stands for a double or a single bond,and to a process for their preparation are provided.Oximation of 4'-demicarosyl-8a-aza-8a-homorelymycin causes breaking of the lactam to obtain a seco compound. The seco compound can be subjected to reductive N-alkylation or to conversion of the hydroxyimino group into a keto group and then optionally to N- or N,O-acylation, a catalytical hydrogenation of the double bond or a reduction of the ketone or a reduction of the hydroxyimino group into an amino group.

摘要翻译： 由式I表示的一类泰乐菌素的Seco化合物，其中R代表H或CH3，R1代表H，CH3，C1-C3酰基或芳基磺酰基，R2代表H，R3代表NH2或OH或R2和 R3一起代表= O或= NOH，R4代表H或C1-C3酰基，线 - - 代表双键或单键，并提供其制备方法。 4'-二去甲酰基-8a-氮杂-8a-茂霉霉素的肟化引起内酰胺的破坏以获得seco化合物。 可以对仲式化合物进行还原N-烷基化或将羟基亚氨基转化为酮基，然后任选地进行N-或N，O-酰化，双键的催化氢化或酮的还原或 将羟基亚氨基还原成氨基。

公开(公告)号：US5922684A

公开(公告)日：1999-07-13

申请号：US959306

申请日：1997-10-28

申请人： Amalija Narandja ,  Nevenka Lopotar

发明人： Amalija Narandja ,  Nevenka Lopotar

IPC分类号： A61K31/70 ,  A61K31/7042 ,  A61K31/7048 ,  A61P31/04 ,  C07H17/08 ,  A61K71/31

CPC分类号： C07H17/08

摘要： The invention relates to 13-hydroxy-tylosine derivatives, novel semisynthetic antibiotics from the class of macrolides, and to a process for the preparation thereof. According to the present invention by a reductive opening of the oxirane ring of tylosine 13-hydroxy compounds are obtained, which are then subjected to a hydrogenation of the double bond and then 13-hydroxy dihydro or tetrahydro compounds are subjected to an oximation reaction or 13-hydroxy oximes are subjected to the hydrogenation of the double bond.

摘要翻译： 本发明涉及13-羟基 - 泰乐菌素衍生物，大环内酯类的新型半合成抗生素及其制备方法。 根据本发明，得到泰乐菌素13-羟基化合物的环氧乙烷环的还原开口，然后进行双键氢化，然后使13-羟基二氢或四氢化合物进行肟化反应或13 - 羟基肟进行双键的氢化。

公开(公告)号：US5023240A

公开(公告)日：1991-06-11

申请号：US180940

申请日：1988-04-13

申请人： Amalija Narandja ,  Bozidar Suskovic ,  Slobodan Djokic ,  Nevenka Lopotar

发明人： Amalija Narandja ,  Bozidar Suskovic ,  Slobodan Djokic ,  Nevenka Lopotar

IPC分类号： A01N43/04 ,  A01P1/00 ,  A61K31/70 ,  A61K31/7042 ,  A61K31/7048 ,  A61P31/04 ,  C07H17/08

CPC分类号： C07H17/08

摘要： Derivatives of tylosin and 10,11,12,13-tetrahydro tylosin of the general formula ##STR1## wherein R stands for CHO, CH.sub.2 OH, CH.dbd.NOH or CH(OCH.sub.3).sub.2,R.sup.1 stands for H,R.sup.2 stands for OH orR.sup.1 +R.sup.2 stand for .dbd.O or .dbd.NOH,R.sup.3 stands for a mycarosyl group or a hydrogen atom, and stands for a single or a double bond;methods for the manufacture thereof; their use as antimicrobial agents and processes for the preparation of the latter.

公开(公告)号：US6077944A

公开(公告)日：2000-06-20

申请号：US38901

申请日：1998-03-12

申请人： Gorjana Lazarevski ,  Gabrijela Kobrehel ,  Amalija Narandja ,  Zrinka Banic-Tomisic

发明人： Gorjana Lazarevski ,  Gabrijela Kobrehel ,  Amalija Narandja ,  Zrinka Banic-Tomisic

IPC分类号： C07H17/08 ,  A61K31/70 ,  A61K31/7048 ,  C07H15/04 ,  C07H15/26 ,  C07H1/00 ,  C07H15/00

CPC分类号： C07H15/04 ,  C07H15/26

摘要： The invention relates to novel secomacrolides from the class of erythromycin A, potential intermediates for preparation of novel macrolide antibiotics general formula ##STR1## and its pharmaceuticaly acceptable addition salts with inorganic or organic acids, wherein R.sub.1 represents hydrogen, C.sub.1 -C.sub.4 alkanoyl group, arylcarbonyl group and together with R.sub.2 and carbon atoms to which they are bound, cyclic carbonyl or thiocarbonyl group, R.sub.2 represents hydrogen or together with R.sub.1 and carbon atoms to which they are bound, cyclic carbonyl or thiocarbonyl group, R.sub.3 represents hydrogen, C.sub.1 -C.sub.4 alkanoyl or arylcarbonyl group,Z is hydrogen or L-cladinosyl group represented by formula (i) ##STR2## wherein R.sub.4 represents hydrogen or C.sub.1 -C.sub.4 alkanoyl group, W is hydrogen or D-desosaminyl group represented by formula (ii) ##STR3## wherein R.sub.5 represents hydrogen or C.sub.1 -C.sub.4 alkanoyl or arylcarbonyl group,X and Y together represent a lactone, or X is CH.sub.2 OR.sub.6, wherein R.sub.6 represents hydrogen or C.sub.1 -C.sub.4 alkanoyl group and Y is hydroxyl group.

摘要翻译： 本发明涉及来自红霉素A类的新型次氯氰菊酯，用于制备新型大环内酯类抗生素通用型的潜在中间体及其与无机或有机酸的药学上可接受的加成盐，其中R1表示氢，C1-C4烷酰基，芳基羰基和一起 R 2和它们所连接的碳原子，环状羰基或硫代羰基，R 2表示氢或与它们所连接的R 1和碳原子一起，环状羰基或硫代羰基，R 3表示氢，C 1 -C 4烷酰基或芳基羰基 Z为氢或由式（ⅰ）表示的L-克拉糖糖基，其中R 4表示氢或C 1 -C 4烷酰基，W为氢或式（ⅱ）表示的D-脱氨基甲酰基，其中R 5表示氢或C 1 -C 4烷酰基或 芳基羰基，X和Y一起表示内酯，或X是CH 2 OR 6，其中R 6表示氢或C 1 -C 4烷酰基，Y是羟基。