公开(公告)号：KR1020000012858A

公开(公告)日：2000-03-06

申请号：KR1019980031401

申请日：1998-08-01

Applicant: 한국과학기술원

Inventor： 김용해 ,  김수기 ,  박일성

IPC: C07K7/50

CPC classification number: A61K38/08 ,  C07K7/50 ,  C07K7/54

Abstract: PURPOSE: The echinomycin derivative is provided to improve the dissolving property to a polar solvent, to reduce the cell poisonous function to normal cells. CONSTITUTION: The synthesis in a form of chloride to maximize the polarity of Echinomycin chloride indicated in a structural formula(1) has the steps of: synthesizing the chloride of Echinomycin using Trialkyloxonium tetrafluoroborate or Meerwein salt or using AgClO4 and methyl iodine. In the chemical formula (1), X represents halogen, sulfate, perchlorate which are possible to synthesize sulfonate salt, in the chemical formula (2), n or m represents the number of oxygen from 0 to 2.

Abstract translation: 目的：提供棘黄霉素衍生物，以改善极性溶剂的溶解性，降低细胞对正常细胞的毒性。 构成：以结构式（1）表示的使氯化青霉素的极性最大化的氯化物合成方法具有以下步骤：使用三烷基氧鎓四氟硼酸盐或米氏盐酸盐或使用AgClO 4和甲基碘合成青霉素的氯化物。 在化学式（1）中，X表示可以合成磺酸盐的卤素，硫酸盐，高氯酸盐，在化学式（2）中，n或m表示0至2的氧数。

公开(公告)号：KR100068203B1

公开(公告)日：1993-12-02

申请号：KR1019910003947

申请日：1991-03-12

Applicant: 한국과학기술원

Inventor： 김용해 ,  임병욱 ,  김권

IPC: C07D251/56

公开(公告)号：KR1019920002565A

公开(公告)日：1992-02-28

申请号：KR1019900011009

申请日：1990-07-19

Applicant: 한국과학기술연구원 ,  한국과학기술원

Inventor： 김용해 ,  이춘호

IPC: C07D277/28 ,  C07D277/58

Abstract: 내용 없음.

公开(公告)号：KR1019910009328B1

公开(公告)日：1991-11-11

申请号：KR1019890020246

申请日：1989-12-29

Applicant: 한국과학기술원

Inventor： 김용해 ,  이춘호

IPC: C07D487/04 ,  C07D473/40

Abstract: A process for preparing 2-furylpurine of formula (I) comprises (a) reacting a purine cpd. of formula (II) with a silylating agent (pref. hexamethyl silazane) to obtain trimethylsilyl cpd., and (b) reacting the obtd. cpd. with 2- acetoxy tetrahydrofurane of formula (III) in an organic solvent (pref. acetonitrile) in the presence of cesium chloride. In the formulas, X = H, NH2 or SH; Y = NH2, Cl, SMe or OH; pref. when X = H, Y = NH2, Cl, SMe or OH; when X = NH2, Y = NH2 or OH; when X = SH, Y = NH2. Cpds. (I) have a antitumor activity.

Abstract translation: 制备式（I）的2-呋喃嘌呤的方法包括（a）使嘌呤cpd反应。 式（II）与甲硅烷基化剂（优选六甲基硅氮烷）反应，得到三甲基甲硅烷基cpd，和（b）使该物质反应。 CPD。 与式（III）的2-乙酰氧基四氢呋喃在有机溶剂（优选乙腈）中）在氯化铯存在下反应。 在式中，X = H，NH2或SH; Y = NH 2，Cl，SMe或OH; 优先。 当X = H时，Y = NH 2，Cl，SMe或OH; 当X = NH 2，Y = NH 2或OH时; 当X = SH时，Y = NH 2。 CPDS。 （I）具有抗肿瘤活性。

公开(公告)号：KR100041414B1

公开(公告)日：1991-04-26

申请号：KR1019880013575

申请日：1988-10-18

Applicant: 한국과학기술원

Inventor： 김용해 ,  김중영

IPC: C07D473/02

公开(公告)号：KR100039652B1

公开(公告)日：1991-02-07

申请号：KR1019880013576

申请日：1988-10-18

Applicant: 한국과학기술원

Inventor： 김용해 ,  김중영 ,  이춘호

IPC: C07D239/32

公开(公告)号：KR100039460B1

公开(公告)日：1991-01-30

申请号：KR1019880003073

申请日：1988-03-22

Applicant: 한국과학기술원

Inventor： 김용해 ,  김중영

IPC: C07D473/02 ,  C07D473/18

公开(公告)号：KR100372759B1

公开(公告)日：2003-02-19

申请号：KR1020000050328

申请日：2000-08-29

Applicant: 한국과학기술원

Inventor： 김용해 ,  김삼민 ,  변일석

IPC: C07F7/18

Abstract: PURPOSE: Provided are a novel (2S,3aS,7aS)-2-(t-butyldiphenylsilyloxymethyl)octahydroindoline of the formula(1) and a process for preparing (2R,3R)-2,3-dialkyltartaric acid by pinacol coupling using it as a chiral ligand, thereby producing (2R,3R)-2,3-dialkyltartaric acid in high chemical and optical yields. CONSTITUTION: (2S,3aS,7aS)-2-(t-butyldiphenylsilyloxymethyl)octahydroindoline is represented by the formula(1), wherein R is methyl or phenyl, and prepared by the steps of: converting (S)-indoline-2-carbonic acid into (S)-indoline-2-carbonic acid ethyl ester using thionyl chloride and ethanol; reducing it by using platinum oxide to obtain (2S,3aS,7aS)-octahydroindole-2-carbonic acid ethyl ester; reducing it by using lithium aluminum hydride; reacting it with chloro t-butyldiphenylsilane acid in the presence of imidazole to obtain (2S,3aS,7aS)-2-(t-butyldiphenylsilyloxymethyl)octahydroindoline. (2R,3R)-2,3-dialkyltartaric acid is prepared by the steps of: reacting 2-keto carbonic acid with (2S,3aS,7aS)-2-(t-butyldiphenylsilyloxymethyl)octahydroindoline(I) in the presence of dicyclohexylcarbodiimide(DDC) to obtain 2-ketoamide(II); pinacol coupling the 2-ketoamide(II) in the presence of hexamethylphosphoamide(HMP) to obtain dialkyltartaric acid derivative; and hydrolyzing the derivative to manufacture (2R,3R)-2,3-dialkyltartaric acid(III).

Abstract translation: 用途：提供了式（1）的新型（2S，3aS，7aS）-2-（叔丁基二苯基甲硅烷氧基甲基）八氢吲哚啉和使用其的频哪醇偶联制备（2R，3R）-2,3-二烷基酒石酸的方法 作为手性配体，由此以高化学和光学产率生产（2R，3R）-2,3-二烷基酒石酸。 结构式（1）表示：（2S，3aS，7aS）-2-（叔丁基二苯基甲硅烷氧基甲基）八氢二氢吲哚，其中R为甲基或苯基，并通过以下步骤制备：将（S） - 二氢吲哚-2- 使用亚硫酰氯和乙醇将碳酸转化成（S） - 二氢吲哚-2-碳酸乙酯; 通过使用氧化铂将其还原以获得（2S，3aS，7aS） - 八氢吲哚-2-碳酸乙酯; 用氢化铝锂还原它; 使其与咪唑存在下的氯叔丁基二苯基硅烷酸反应，得到（2S，3aS，7aS）-2-（叔丁基二苯基甲硅烷基氧基甲基）八氢二氢吲哚。 通过以下步骤制备（2R，3R）-2,3-二烷基酒石酸：在二环己基碳二亚胺存在下使2-酮基碳酸与（2S，3aS，7aS）-2-（叔丁基二苯基甲硅烷氧基甲基）八氢二氢吲哚（I） （DDC）以获得2-酮酰胺（II）; 频哪醇在六甲基磷酰胺（HMP）存在下偶联2-酮酰胺（II）以获得二烷基酒石酸衍生物; 并水解该衍生物以制造（2R，3R）-2,3-二烷基酒石酸（III）。

公开(公告)号：KR100372758B1

公开(公告)日：2003-02-19

申请号：KR1020000050327

申请日：2000-08-29

Applicant: 한국과학기술원

Inventor： 김용해 ,  김삼민 ,  변일석

IPC: C07F7/18

Abstract: PURPOSE: Provided are a novel (S)-2-t-butyldiphenylsilyloxymethylindoline of the formula(1) and a process for preparing (2S,3S)-2,3-dialkyltartaric acid by pinacol coupling using it as a chiral ligand, thereby producing (2S,3S)-2,3-dialkyltartaric acid in high chemical and optical yields. CONSTITUTION: (S)-2-t-butyldiphenylsilyloxymethylindoline is represented by the formula(1), wherein R is methyl or phenyl, and prepared by the steps of: reducing (S)-indoline-2-carbonic acid into lithium aluminum hydride; reacting it with chloro t-butyldiphenylsilane compound in the presence of imidazole to obtain (S)-2-t-butyldiphenylsilyloxymethylindoline. (2S,3S)-2,3-dialkyltartaric acid is prepared by the steps of: reacting 2-keto carbonic acid with (S)-2-t-butyldiphenylsilyloxymethylindoline(I) in the presence of dicyclohexylcarbodiimide(DDC) to obtain 2-ketoamide(II); pinacol coupling the 2-ketoamide(II) in the presence of hexamethylphosphoamide(HMP) to obtain dialkyltartaric acid derivative; and hydrolyzing the derivative to manufacture (2S,3S)-2,3-dialkyltartaric acid(III).

Abstract translation: 用途：提供了式（1）的新型（S）-2-叔丁基二苯基甲硅烷氧基甲基二氢吲哚和使用频哪醇偶合制备（2S，3S）-2,3-二烷基酒石酸作为手性配体，从而制备 （2S，3S）-2,3-二烷基酒石酸，其化学和光学产率高。 结构式：（S）-2-叔丁基二苯基甲硅烷氧基甲基二氢吲哚由式（1）表示，其中R为甲基或苯基，并通过以下步骤制备：将（S） - 二氢吲哚-2-碳酸还原成氢化铝锂; 使其与氯叔丁基二苯基硅烷化合物在咪唑存在下反应，得到（S）-2-叔丁基二苯基甲硅烷氧基甲基二氢吲哚。 （DDC）存在下使2-酮基碳酸与（S）-2-叔丁基二苯基甲硅烷氧基甲基二氢吲哚（I）反应，制得2-（2S，3S）-2,3-二烷基酒石酸， 酮酰胺（II）; 频哪醇在六甲基磷酰胺（HMP）存在下偶联2-酮酰胺（II）以获得二烷基酒石酸衍生物; 并水解衍生物以制备（2S，3S）-2,3-二烷基酒石酸（III）。

公开(公告)号：KR100295269B1

公开(公告)日：2001-11-15

申请号：KR1019980031401

申请日：1998-08-01

Applicant: 한국과학기술원

Inventor： 김용해 ,  김수기 ,  박일성

IPC: C07K7/50

Abstract: 본 발명은 항암제로 알려져 있는 이치노마이신을 이용한 신규한 이치노마이신 유도체의 합성에 관한 것이다. 이치노마이신은 현재 임상실험 2단계(Phase II)에 있는 물질로서 정상세포에 대한 세포독성이 강하고 극성용매에 대한 용해도가 낮아 항암제로 사용하기에는 많은 문제점이 있다.
본 발명에 의해 합성된 이치노마이신의 황산화 유도체 및 술포니움 유도체는 극성기의 도입 및 염화물 형태로 유도체화 하였기 때문에 극성 용매에 대한 용해도 향상 및 정상 세포에 대한 세포독성 등을 감소시켜 문제점을 해결하였다. 본 발명의 화합물을 합성한 후 순수 분리 및 정제하여 항암력을 측정하였던 바 황원소의 산화반응을 통해 합성한 술폭사이드, 디술폭사이드, 술폰 등은 항암력이 크게 개선되지 못하였으며 술폭사이드에서만 약간 독성이 감소하는 결과를 얻었다. 그러나 황원소의 술포니움염 합성 반응을 통해 얻은 화합물은 항암력이 유지되면서 정상세포에 대한 세포 독성능이 100배 이상 감소된 결과를 얻을 수 있었다.