公开(公告)号：US5101022A

公开(公告)日：1992-03-31

申请号：US650060

申请日：1991-02-04

申请人： Hamao Umezawa ,  Sumio Umezawa ,  Tsutomu Tsuchiya ,  Tomio Takeuchi ,  Akihiro Tanaka ,  Shuichi Sakamoto

发明人： Hamao Umezawa ,  Sumio Umezawa ,  Tsutomu Tsuchiya ,  Tomio Takeuchi ,  Akihiro Tanaka ,  Shuichi Sakamoto

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

CPC分类号： C07H17/08 ,  Y02P20/55

摘要： Mycaminosyl tylonolide derivatives represented by the following general formula ##STR1## (wherein R.sup.1 denotes hydroxyl group, a lower alkanoyloxy group, benzoyloxy group, azido group, or amino group which may optionally be substituted with a lower alkyl or a lower alkanoyl radical; R.sup.2 stands for hydrogen atom or hydroxyl group; R.sup.3 expresses hydrogen atom or formyl group; and means a double bond or a radical represented by ##STR2## and salts thereof.

公开(公告)号：US5034517A

公开(公告)日：1991-07-23

申请号：US488871

申请日：1990-03-06

申请人： Hamao Umezawa ,  Sumio Umezawa ,  Tsutomu Tsuchiya ,  Tomio Takeuchi ,  Yasushi Takagi

发明人： Hamao Umezawa ,  Sumio Umezawa ,  Tsutomu Tsuchiya ,  Tomio Takeuchi ,  Yasushi Takagi

IPC分类号： A61K31/70 ,  A61K31/7024 ,  A61K31/7028 ,  A61K31/7034 ,  A61K31/704 ,  A61P31/04 ,  C07H1/00 ,  C07H5/02 ,  C07H13/04 ,  C07H13/06 ,  C07H15/04 ,  C07H15/252

CPC分类号： C07H5/02 ,  C07H13/04 ,  C07H15/04 ,  Y02P20/55

摘要： 2,6-Dideoxy-2-fluoro-L-talopyranose and 1-substituted derivatives thereof, including methyl 2,6-dideoxy-2-fluoro-L-talopyranoside and 3,4-di-O-protected-2,6-dideoxy-2-fluoro-L-talopyranosyl halides, are now provided and these new compounds are useful as intermediates for use in the synthesis of new compounds having antitumor activity, especially 7-O-(2,6-dideoxy-2-fluoro-.alpha.-L-talopyranosyl) daunomycinone or -adriamycinone. 2,6-Dideoxy-2-fluoro-L-talopyranose shows antibacterial activity. 2,6-Dideoxy-fluoro-L-talopyranose and the 1-substituted derivatives thereof may be produced by a multi-stage process starting from L-fucose.

摘要翻译： 2,6-二脱氧-2-氟-L-吡喃葡萄糖及其1-取代衍生物，包括2,6-二脱氧-2-氟-L-吡喃葡萄糖苷和3,4-二-O-保护的2,6-二 现在提供二脱氧-2-氟-L-吡喃葡萄糖基卤化物，这些新化合物可用作合成具有抗肿瘤活性的新化合物的中间体，特别是7-O-（2,6-二脱氧-2-氟 - α-L-吡喃葡萄糖基）道诺霉素或阿霉素酮。 2,6-二脱氧-2-氟-L-吡喃葡萄糖显示出抗菌活性。 2,6-二脱氧 - 氟-L-吡喃葡萄糖及其1-取代衍生物可以通过从L-岩藻糖开始的多阶段方法制备。

公开(公告)号：US4661474A

公开(公告)日：1987-04-28

申请号：US807485

申请日：1985-12-10

申请人： Hamao Umezawa ,  Sumio Umezawa ,  Tsutomu Tsuchiya ,  Yoshiaki Takahashi

发明人： Hamao Umezawa ,  Sumio Umezawa ,  Tsutomu Tsuchiya ,  Yoshiaki Takahashi

IPC分类号： C07H15/236 ,  A61K31/71 ,  C07H15/234

CPC分类号： C07H15/234 ,  Y02P20/55

摘要： New compounds, 2',3'-dideoxy-2'-fluorokanamycin A and 1-N-(.alpha.-hydroxy-.omega.-aminoalkanoyl) derivatives thereof, particularly 1-N-(DL- or L-3-amino-2-hydroxypropionyl)- and 1-N-(L-4-amino-2-hydroxybutyryl)-2',3'-dideoxy-2'-fluorokanamycins A are now provided, which are each useful as antibacterial agent. 2',3'-Dideoxy-2'-fluorokanamycin A is prepared by a process comprising condensing a 6-azido-4-O-protected-2,3,6-trideoxy-2-fluoro-.alpha.-D-ribo-hexopyranosyl bromide with the 4-hydroxyl group of a 6-O-(2',4',6'-tri-O-protected-3'-N-protected-3'-amino-3'-deoxy-.alpha.-D-glucopyranosyl)-1,3-bis-N-protected-2-deoxystreptamine, reducing the resulting condensation product to convert its azido group into an amino group, and removing the remaining amino-protecting and hydroxyl-protecting groups from the reduction product.

摘要翻译： 新化合物2'，3'-二脱氧-2'-氟卡那霉素A及其1-N-（α-羟基-ω-氨基烷酰基）衍生物，特别是1-N-（DL-或L-3-氨基-2- 羟基丙酰基） - 和1-N-（L-4-氨基-2-羟基丁酰基）-2'，3'-二脱氧-2'-氟吗啉霉素A，其各自可用作抗菌剂。 2'，3'-二脱氧-2'-氟卡那霉素A通过以下方法制备，该方法包括将6-叠氮基-4-O-保护的2,3,6-三脱氧-2-氟-α-D-吡喃六氟肉豆蔻基 溴化物与6-O-（2'，4'，6'-三-O-保护的3'-N-保护的-3'-氨基-3'-脱氧-α-D- D-吡喃葡萄糖基）-1,3-双-N-保护的2-脱氧链霉胺，将所得缩合产物还原，将其叠氮基转化为氨基，并从还原产物中除去剩余的氨基保护基和羟基保护基团。

公开(公告)号：US4473557A

公开(公告)日：1984-09-25

申请号：US475269

申请日：1983-03-09

申请人： Hamao Umezawa ,  Sumio Umezawa ,  Tsutomu Tsuchiya ,  Takayuki Usui

发明人： Hamao Umezawa ,  Sumio Umezawa ,  Tsutomu Tsuchiya ,  Takayuki Usui

IPC分类号： A61K31/70 ,  A61K31/7028 ,  A61K31/7034 ,  A61K31/7036 ,  A61P31/04 ,  C07H15/238 ,  A61K31/71 ,  C07H15/22

CPC分类号： C07H15/238 ,  Y02P20/55

摘要： A new semi-synthetic antibiotic, 3"-deoxystreptomycin is now provided, which is useful as an antibacterial agent and is produced from 3"-deoxydihydrostreptomycin by a process comprising oxidizing the 3'-hydroxymethyl group of 2,5,6,4",6"-penta-O-acetyl-2"-N-benzyloxycarbonyl-3"-deoxydihydrostreptomycin as prepared by skilled introduction of amino-protecting group and hydroxyl-protecting group of appropriately selected natures into 3"-deoxydihydrostreptomycin, and then removing the protective groups from the oxidation product, 2,5,6,4",6"-penta-O-acetyl-2"-N-benzyloxycarbonyl-3"-deoxystreptomycin.

摘要翻译： 现在提供一种新的半合成抗生素3'-脱氧链霉素，其可用作抗菌剂并且由3'-脱氧双氢链霉素通过包括氧化2,5,6的3'-羟甲基的方法制备， 4“，6” - 五-O-乙酰基-2“ - N-苄氧羰基-3” - 脱氧二氢嘧啶霉素，由熟练引入氨基保护基和适当选择的性质的羟基保护基制成3' 脱氧链霉素，然后从氧化产物2,5,6,4'，6“ - 五-O-乙酰基-2”-N-苄氧羰基-3“ - 脱氧链霉素中除去保护基团。

公开(公告)号：US4008362A

公开(公告)日：1977-02-15

申请号：US390217

申请日：1973-08-21

申请人： Eiichi Akita ,  Tsutomu Tsuchiya ,  Shinichi Kondo ,  Shuntaro Yasuda ,  Sumio Umezawa ,  Hamao Umezawa

发明人： Eiichi Akita ,  Tsutomu Tsuchiya ,  Shinichi Kondo ,  Shuntaro Yasuda ,  Sumio Umezawa ,  Hamao Umezawa

IPC分类号： A61K31/70 ,  A61K31/7028 ,  A61K31/7034 ,  A61K31/7036 ,  A61K31/704 ,  A61P31/04 ,  C07H15/224 ,  C07H15/23 ,  C07H15/244

CPC分类号： C07H15/224 ,  C07H15/23

摘要： An 1-N-((S)-.alpha.-substituted-.omega.-aminoacyl)-neamine or -ribostamycin of the formula ##STR1## wherein R is a hydrogen atom or .beta.-D-ribofuranosyl group of the formula ##STR2## and R.sub.3 is hydroxyl, amino-NH.sub.2 or acylamino group --NHR.sub.4 in which R.sub.4 is an acyl group, and n is a whole number of 1 to 4, may be produced by subjecting the corresponding O-((S)-.alpha.-substituted-.omega.-aminoacyl)-neamine or -ribostamycin of the formula ##STR3## or its hydroxyl-masked and maino-masked form, to the action of a basic medium to produce an acyl-migration product of the formula: ##STR4## and, optionally converting the amino-masking groups into hydrogen atoms and also the hydroxyl-masking group into hydroge atom in a known manner if said amino-masking groups and said hydroxyl-masking groups are present in the acyl-migration product. The 1-N-((S)-.alpha.-substituted-.omega.-aminoacyl)-neamine or -ribostamycin produced is characterized by its useful activity inhibitory to the growth of bacteria resistant to the parent substance neamine or ribostamycin.

摘要翻译： 式（1）的1-N - （（S）-α-取代的ω-氨基酰基） - 单胺或-ribostamycin，其中R为氢原子或式为“IMAGE”的β-D-呋喃核糖基，R3为 是其中R 4为酰基，n为整数1至4的羟基，氨基-NH 2或酰基氨基-NHR 4，其可以通过使相应的O - （（S）-α-取代的ω- 氨基酰基） - 奈米霉素或结晶霉素或其羟基掩蔽和主掩蔽形式，与碱性介质的作用产生下式的酰基迁移产物：和/或将 如果所述氨基掩蔽基团和所述羟基掩蔽基团存在于酰基迁移产物中，则以已知方式将氨基掩蔽基团转化成氢原子，并将羟基掩蔽基团转变成水解原子。 产生的1-N - （（S）-α-取代的ω-氨基酰基） - 单胺或 - 生物素 - 特异霉素的特征在于其对母体neamine或核糖霉素具有抗性的细菌的生长有抑制作用。

公开(公告)号：US4008218A

公开(公告)日：1977-02-15

申请号：US559771

申请日：1975-03-19

申请人： Eiichi Akita ,  Tsutomu Tsuchiya ,  Shinichi Kondo ,  Shuntaro Yasuda ,  Sumio Umezawa ,  Hamao Umezawa

发明人： Eiichi Akita ,  Tsutomu Tsuchiya ,  Shinichi Kondo ,  Shuntaro Yasuda ,  Sumio Umezawa ,  Hamao Umezawa

IPC分类号： C07H15/224 ,  C07H15/23 ,  C07G11/00

CPC分类号： C07H15/224 ,  C07H15/23

摘要： An 1-N-((S)-.alpha.-substituted-.omega.-aminoacyl)-neamine or -ribostamycin of the formula: ##STR1## wherein R is a hydrogen atom or .beta.-D-ribofuranosyl group of the formula ##STR2## and R.sub.3 is hydroxyl, amino-NH.sub.2 or acylamino group --NHR.sub.4 in which R.sub.4 is an acyl group, and n is a whole number of 1 to 4, may be produced by subjecting the corresponding O-((S)-.alpha.-substituted-.omega.-aminoacyl)-neamine or -ribostamycin of the formula ##STR3## or its hydroxyl-masked and amino-masked form, to the action of a basic medium to produce an acyl-migration product of the formula: ##STR4## and, optionally converting the amino-masking groups into hydrogen atoms and also the hydroxyl-masking group into hydrogen atom in a known manner if said amino-masking groups and said hydroxyl-masking groups are present in the acyl-migration product. The 1-N-((S)-.alpha.-substituted-.omega.-aminoacyl)-neamine or -ribostamycin produced is characterized by its useful activity inhibitory to the growth of bacteria resistant to the parent substance neamine or ribostamycin.

摘要翻译： 具有下式的1-N - （（S）-α-取代的ω-氨基酰基） - 微量胺或 - 瑞波霉素：其中R是式“IMAGE”的氢原子或β-D-呋喃核糖基， R 3是羟基，氨基-NH 2或酰基氨基-NHR 4，其中R 4是酰基，n是整数1至4，可以通过使相应的O - （（S）-α-取代的-ω- - 氨基酰基） - 或者其羟基掩蔽和氨基掩蔽形式的微生物胺或β-内啡霉素或碱性培养基，以产生下式的酰基迁移产物： 如果所述氨基掩蔽基团和所述羟基掩蔽基团存在于酰基迁移产物中，则以已知的方式将氨基掩蔽基团转化成氢原子，并将羟基掩蔽基团转变为氢原子。 产生的1-N - （（S）-α-取代的ω-氨基酰基） - 单胺或 - 生物霉素的特征在于其对母体neamine或核糖霉素具有抗性的细菌的生长有抑制作用。

公开(公告)号：US4455419A

公开(公告)日：1984-06-19

申请号：US398838

申请日：1982-07-16

申请人： Hamao Umezawa ,  Sumio Umezawa ,  Yoshiharu Ishido ,  Shunzo Fukatsu

发明人： Hamao Umezawa ,  Sumio Umezawa ,  Yoshiharu Ishido ,  Shunzo Fukatsu

IPC分类号： C07H15/234 ,  A61K31/70 ,  A61K31/7028 ,  A61K31/7034 ,  A61K31/7036 ,  A61P31/04 ,  C07H15/236 ,  C07H15/22

CPC分类号： C07H15/234 ,  Y02P20/55

摘要： 2'-Modified kanamycins, including 2'-deoxykanamycin A, 2'-epikanamycin A and 2'-epikanamycin B, as new compounds are produced starting from kanamycin A by consecutive reaction steps. These new compounds are useful as antibacterial agent.

摘要翻译： 通过连续的反应步骤从卡那霉素A开始制备作为新化合物的2'-改性的卡那霉素，包括2'-脱氧卡那霉素A，2'-表阿卡那霉素A和2'-表卡霉素B。 这些新化合物可用作抗菌剂。

公开(公告)号：US4359572A

公开(公告)日：1982-11-16

申请号：US256131

申请日：1981-04-21

申请人： Hamao Umezawa ,  Sumio Umezawa ,  Shunzo Fukatsu ,  Toshio Yoneta

发明人： Hamao Umezawa ,  Sumio Umezawa ,  Shunzo Fukatsu ,  Toshio Yoneta

IPC分类号： C07H15/234 ,  C07H15/236 ,  A61K31/71 ,  C07H15/22

CPC分类号： C07H15/234 ,  Y02P20/55

摘要： 3'-Deoxykanamycin A useful as an antibacterial agent can be produced by a new process comprising reacting a 2',2"-di-O-acylated-3'-O-sulfonylated-tetra-N-protected derivative of kanamycin A with a base such as alkali metal alcoholate in a lower alkanol to effect 2',3'- and 3',4'-epoxidation and concurrently removal of the 2'- and 2"-acyl groups, reducing the resultant N-protected 2',3'-anhydro-3'-epi derivative and 3',4'-anhydro-3'-epi derivative of kanamycin A either with hydrogen in the presence of a known hydrogenation catalyst or with sodium borohydride to afford the corresponding N-protected 3'-deoxygenated derivative of kanamycin A and then removing the residual amino-protecting groups therefrom to give 3'-deoxykanamycin A.

摘要翻译： 可用作抗菌剂的3'-脱氧卡那霉素A可以通过新的方法制备，包括使卡那霉素A的2'，2“ - 二-O-酰化-3'-O-磺酰化四-N-保护的衍生物与 碱如碱金属醇化物在低级链烷醇中进行2'，3'和3'，4'-环氧化并同时去除2'-和2“ - 酰基，将所得N-保护的2 '，3'-脱水-3'-外延衍生物和卡那霉素A的3'，4'-脱氢-3'-epi衍生物，与已知氢化催化剂或硼氢化钠存在下的氢气反应，得到相应的N- 保护的卡那霉素A的3'-脱氧衍生物，然后从其中除去残留的氨基保护基，得到3'-脱氧卡那霉素A.

公开(公告)号：US4195170A

公开(公告)日：1980-03-25

申请号：US880401

申请日：1978-02-23

申请人： Hamao Umezawa ,  Sumio Umezawa ,  Shigeo Seki ,  Shunzo Fukatsu ,  Shuntaro Yasuda

发明人： Hamao Umezawa ,  Sumio Umezawa ,  Shigeo Seki ,  Shunzo Fukatsu ,  Shuntaro Yasuda

IPC分类号： C07H15/236 ,  C07H15/22

CPC分类号： C07H15/234 ,  Y02P20/55

摘要： New routes are provided for the synthesis of 3',4'-dideoxykanamycin B which is effective in inhibiting kanamycin-resistant organisms from kanamycin B through new intermediate, of which a fundamental process comprises a new reaction of a 3',4'-epoxy derivative of amino- and hydroxyl-protected kanamycin B with a xanthate to form a corresponding 3',4'-dideoxy-3'-eno derivative followed by removal of the amino- and hydroxyl-protecting groups thereof and by hydrogenation of the resulting 3',4'-dideoxy-3'-eno-kanamycin B. A 3',4'-episulfide derivative corresponding to the 3',4'-epoxy derivative which is formed as second product in the reaction of 3',4'-epoxy derivative with xanthate is also used as intermediate for the preparation of 3',4'-dideoxykanamycin B.

摘要翻译： 提供了用于合成3'，4'-双脱氧卡那霉素B的新途径，其通过新的中间体有效抑制卡那霉素B的卡那霉素抗性生物，其中基本方法包括3'，4'-环氧基 氨基和羟基保护的卡那霉素B与黄原酸酯的衍生物形成相应的3'，4'-二脱氧-3'-烯衍生物，然后除去其氨基和羟基保护基团，并通过氢化得到的3 '，4'-二脱氧-3'-烯 - 卡那霉素B.对应于3'，4'-环氧衍生物的3'，4'-环硫化物衍生物，其在3'，4' 含有黄原酸酯的环氧衍生物也用作制备3'，4'-双脱氧卡那霉素B的中间体。

公开(公告)号：US4147861A

公开(公告)日：1979-04-03

申请号：US865470

申请日：1977-12-29

申请人： Hamao Umezawa ,  Kenji Maeda ,  Shinichi Kondo ,  Sumio Umezawa

发明人： Hamao Umezawa ,  Kenji Maeda ,  Shinichi Kondo ,  Sumio Umezawa

IPC分类号： C07H15/236 ,  C07H15/22

CPC分类号： C07H15/234

摘要： A number of 1N-(.alpha.-hydroxy-.omega.-aminoalkanoyl)-6'N-methyl-3',4'-dideoxykanamycin B derivatives have been found to possess excellent antibacterial activity against most kanamycin susceptible and resistant organisms. In particular, 1N-(DL-isoseryl)-6'N-methyl-3',4'-dideoxykanamycin B, 1N-(L-isoseryl)-6'-N-methyl-3',4'-dideoxykanamycin B, 1N-(L-4-amino-2-hydroxybutyryl)-6'N-methyl-3',4'-dideoxykanamycin B and 1N-(L-5-amino-2-hydroxyvaleryl)-6'N-methyl-3',4'-dideoxykanamycin B, or an acid addition salt thereof possess these highly desirable attributes.

摘要翻译： 已经发现许多1N-（α-羟基 - ω-氨基烷酰基）-6'N-甲基-3'，4'-双脱氧卡那霉素B衍生物对大多数卡那霉素敏感和抗性生物具有优异的抗菌活性。 特别是1N-（DL-异丝氨酰基）-6'N-甲基-3'，4'-二脱氧卡那霉素B，1N-（L-异丝氨酰基）-6'-N-甲基-3'，4'-二脱氧卡那霉素B， 1N-（L-4-氨基-2-羟基丁酰基）-6'N-甲基-3'，4'-二脱氧卡那霉素B和1N-（L-5-氨基-2-羟基戊酰基）-6'N-甲基-3 '，4'-双脱氧卡那霉素B或其酸加成盐具有这些非常理想的特性。