公开(公告)号：US3741955A

公开(公告)日：1973-06-26

申请号：US3741955D

申请日：1971-04-06

Applicant: HOECHST AG

Inventor： FRITSCH W ,  HAEDE W ,  RADSCHEIT K ,  STACHE U ,  LINDNER E

IPC: A61K31/70 ,  C07J71/00 ,  C07C173/00

CPC classification number: A61K31/70 ,  C07J71/00

Abstract: CARDIOACTIVE 3B - HYDROXY-14,15B-OXIDO-14B-BUFA-4,20, 22-TRIENOLIDE-3B-(A-L-RHAMNOPYRANOSIDE). METHOD OF MAKING THIS COMPOUND BY ACYLATING AND DEHYDRATING PROSCILLARDIN, FORMING A HALOHYDRIN FROM THE RESULTING $14-OLEFIN, DEHYDROGALOGENATING TO FORM THE 14,15B-EPOXIDE, AND HYDROLYZING TO FORM THE FREE LRHAMNOPYRANOSIDE.

公开(公告)号：US3732210A

公开(公告)日：1973-05-08

申请号：US3732210D

申请日：1971-01-26

Applicant: HOECHST AG

Inventor： STACHE U ,  FRITSCH W ,  HAEDE W ,  RADSCHEIT K

IPC: C07D20060101 ,  C07J5/00 ,  C07J71/00 ,  C07C173/00

CPC classification number: C07J17/00

Abstract: A PROCESS FOR THE MANUFACTURE OF PREGNANE-20-ONE3B,5B,14B,21-TETROL, USEFUL AS A STARTING MATERIAL FOR PHARMACEUTICALLY VALUABLE COMPOUNDS OF THE PREGNANE SERIES, BY CONVERTING $414-PREGNADIENE-3,20-DIONE-21-OL TO THE CORRESPONDING 3,20-BIS-ALKYLENE-DIOXY-$5,14-PREGNADIENE21-OL WIT ETHYLENE GLYCOL OR NEOPENTYL GLYCOL, ACYLATING TO FORM THE 21-ACYLATE AND THEN PARTIALLY DE-KETALIZING THE ACYLATE TO PRODUCE 20-ALKYLENE-DIOXY-$4,14-PREGNADIENE-3ONE-21-ACYLATE, REDUCING THE 3-KETO GROUP WITH AN ORGANOMETALLIC REDUCING AGENT, WHEREBY THE 21-ACYLATE GROUP MAY ALSO BE CONVERTED BY THE REDUCING AGENT TO THE 21-OL, ACYLATING THE 20-ALKYLENE-DIOXY-$4,14-PREGNADIENE-3,21-DIOL OR -3-OL-21-ACYLATE TO FORM 20-ALKYLENE-DIOXY-$4,14PREGNADIENE-3,21-DIACYLTE, TREATING THIS WITH HYPOBROMOUS ACID TO FORM 5A,15A-DIBROMO-20-ALKYLENE-DIOXY-PREGNANE-3B,5B,14B,21-TETROL-3,21-DIACYLATE AND DEBROMINATING WITH A BASE TO FORM 20-ALKYLENE-DIOXY-4B(5B), 14B(15BDIOXIDO-PREGNANE-3B,21-DIOL OR THE CORRESPONDING -3,21-DIACYLATE, AND REDUCING TO 20-ALKYLENE-DIOXY-PREGNANE-3B, 5B,14B,21-TETROL WITH AN ORGANOMETALLIC REDUCING AGENT. THE 20-ALKYLENE-DIOXY GROUP IS HYDROLYZED TO FORM THE DESIRED PREGNANE 20-ONE-3B,5B,14B,21-TETROL, WHICH MAY BE FURTHER REATED WITH DIHYDROPYRANE TO FORM THE CORRESPONDING -3B,21-DITETRAHYDROPYRANYL ETHER.

公开(公告)号：US3725393A

公开(公告)日：1973-04-03

申请号：US3725393D

申请日：1971-10-18

Applicant: HOECHST AG

Inventor： STACHE U ,  FRITSCH W ,  HAEDE W ,  RADSCHEIT K ,  LINDNER E

IPC: A61K20060101 ,  C07D20060101 ,  C07J19/00 ,  C07C173/02

CPC classification number: C07J75/00

Abstract: 3-N-alkyl-amino-cardenolides of the general formula

Abstract translation: 其中R 1表示氢或β-羟基的通式的3-N-烷基 - 氨基 - 己烯酸烯; R 2和R 3各自表示氢或羟基，或者R 2和R 3一起代表另外的C-C键或α或β-氧代基; R4，R5，R6和R7各自表示氢或可被酯化的羟基 - R6的OH-基团也可以醚化 - ; R8代表氢或羟基; 并且R 9表示可以含有一个或多个OH-基团的碳原子数1〜6的烷基或芳脂肪族基团，及其与无机酸或有机酸的盐。 这些化合物具有有价值的药理学性质，特别是正或负性肌力作用，并且在脂质中具有显着改善的溶解性。

公开(公告)号：AT335078B

公开(公告)日：1977-02-25

申请号：AT583871

申请日：1971-07-06

Applicant: HOECHST AG

Inventor： STACHE U ,  RADSCHEIT K ,  FRITSCH W ,  HAEDE W

IPC: C07D20060101 ,  C07J19/00

Abstract: 1362383 Cardenolides; bufadienolides FARBWERKE HOECHST AG 7 July 1971 [7 July 1970] 31974/71 Heading C2U [Also in Division A5] The invention comprises (A) the compounds 3#,14 - dihydroxy - 5α,14# - bufa - 20,22 - dienolide (Ia); 3#-hydroxy-5α,14α-card-20(22)- enolide; 3# - hydroxy - 5α - bufa - 14,20,22- trienolide; and 3#-hydroxy-5α,14α-bufa-20,22- dienolide; and (B) a process for preparing compounds of formula (wherein R 1 is the lactone ring of a 20(22)- cardenolide or 20,22-bufadienolide; R 2 is CH 3 , CH 2 OH or CH 2 OCOCH 3 ; R 3 is H, OH or acyloxy; R 4 is H; or R 3 + R 4 is epoxy or an extra C-C bond; and R 5 and R 6 are each H, OH or acyloxy) which comprises reducing the corresponding 3-oxo-# 4 compounds (wherein R 2 is alternatively CHO and R 5 and R 6 are each alternatively oxo) with a reducing agent which is more powerful than NaBH 4 , in the presence of an organic nitrogen base at - 30‹ to + 60‹ C. Any oxo groups at positions 11, 12 and 19 are reduced concomitantly. Specified reducing agents are the borohydrides of Li, Mg, Ca, Sr, Ba, Zn and Al, the trimethoxy borohydrides of Na and Li, the aluminium hydrides of Na, Li and Mg, aluminium hydride, lithium trimethoxy aluminium hydride, diborane, pyridine-borane, ethane-1,2- diamine-borane and (3-methyl-2-butyl)borane. Compound Ia supra is alternatively prepared from 3# - hydroxy - 5α - bufa - 14,20,22 - trienolide (III) by the sequence : III # III 3- formate # 15α-bromo-(Ia)-3-formate # Ia 3-formate -# Ia. 3 - Oxo - 14α - bufa - 4,20,22 - trienolide is prepared from the corresponding # 5 -3#-ol by Oppenauer oxidation. Compounds I are said to be cardiotonic, and may be made up with carriers into pharmaceutical compositions for oral and parenteral administration.

公开(公告)号：SE387349B

公开(公告)日：1976-09-06

申请号：SE7314221

申请日：1973-10-19

Applicant: HOECHST AG

Inventor： STACHE U ,  RADSCHEIT K

IPC: C07J31/00 ,  C07D20060101 ,  C07J1/00 ,  C07J17/00 ,  C07J19/00 ,  C07J21/00

Abstract: The present invention relates to an improved process for the manufacture of beta -(3-oxo-7 alpha -thioacyl-17 beta -hydroxy-4-androsten-17 alpha -yl)-propionic acid gamma -lactones, in which a beta -(3-oxo-17 beta -hydroxy-4,6-androstadien-17 alpha -yl)-propionaldehyde dialkyl or alkylene acetal is reacted with a thiocarboxylic acid, in a mixture of water an an organic solvent miscible with water, to yield a beta -(3'-oxo-7' alpha -thioacyl-17 beta '-hydroxy-4'-androsten-17 alpha -yl)-propionaldehyde-dialkyl or alkylene acetal and in which this compound is oxidized in an acid solution to yield the corresponding gamma -lactone.

公开(公告)号：SE386188B

公开(公告)日：1976-08-02

申请号：SE7313472

申请日：1973-10-03

Applicant: HOECHST AG

Inventor： STACHE U ,  RADSCHEIT K

IPC: C07D20060101 ,  C07J31/00 ,  C07J19/00 ,  C07J21/00

Abstract: The present invention relates to an improved process for the manufacture of beta -(3-oxo-7 alpha -thioacyl-17 beta -hydroxy-4-androstene-17 alpha -yl)-propionic acid gamma -lactones in which a beta -(3-oxo-17 beta -hydroxy-4,6-androstadiene-17 gamma -yl)-propionaldehyde cyclohemiacetal alkyl glycoside is reacted with a thiocarboxylic acid in a mixture of water and an organic solvent miscible with water to yield a 3-(3'-oxo-7 alpha '-thioacyl-17 beta '-hydroxy-4'-androstene-17 alpha '-yl)-propionaldehyde cyclohemiacetal alkyl glycoside and in which the compound thus obtained is oxidized in an acid solution, the alkyl glycoside radical in the cyclohemiacetal group being split off, to yield the corresponding gamma -lactone; the invention further relates to new intermediates useful in this process and having the formula IN WHICH R1 stands for the methyl group or a hydrogen atom and R2 and R3 each for an alkyl group having 1 to 5 carbon atoms.

公开(公告)号：DK131865C

公开(公告)日：1976-02-16

申请号：DK539973

申请日：1973-10-04

Applicant: HOECHST AG

Inventor： STACHE U ,  RADSCHEIT K

IPC: C07D20060101 ,  C07J31/00 ,  C07J19/00 ,  C07J21/00

Abstract: The present invention relates to an improved process for the manufacture of beta -(3-oxo-7 alpha -thioacyl-17 beta -hydroxy-4-androstene-17 alpha -yl)-propionic acid gamma -lactones in which a beta -(3-oxo-17 beta -hydroxy-4,6-androstadiene-17 gamma -yl)-propionaldehyde cyclohemiacetal alkyl glycoside is reacted with a thiocarboxylic acid in a mixture of water and an organic solvent miscible with water to yield a 3-(3'-oxo-7 alpha '-thioacyl-17 beta '-hydroxy-4'-androstene-17 alpha '-yl)-propionaldehyde cyclohemiacetal alkyl glycoside and in which the compound thus obtained is oxidized in an acid solution, the alkyl glycoside radical in the cyclohemiacetal group being split off, to yield the corresponding gamma -lactone; the invention further relates to new intermediates useful in this process and having the formula IN WHICH R1 stands for the methyl group or a hydrogen atom and R2 and R3 each for an alkyl group having 1 to 5 carbon atoms.

公开(公告)号：CH572069A5

公开(公告)日：1976-01-30

申请号：CH1559971

申请日：1971-10-26

Applicant: HOECHST AG

Inventor： STACHE U ,  FRITSCH W ,  HAIDE W ,  RADSCHEIT K ,  LINDNER

IPC: A61K20060101 ,  A61K31/585 ,  C07C20060101 ,  C07D20060101 ,  C07J17/00 ,  C07J41/00

公开(公告)号：NO132432C

公开(公告)日：1975-11-19

申请号：NO157269

申请日：1969-04-17

Applicant: HOECHST AG

Inventor： KOHL H ,  FRITSCH W ,  HAEDE W ,  RADSCHEIT K ,  STACHE U

IPC: B01J25/02 ,  C07J19/00

Abstract: 1275421 Cardioactive medicines FARBWERKE HOECHST AG 28 April 1969 [27 April 1968] 21595/69 Heading A5B [Also in Division C2] Pharmaceutical compositions comprise a carrier and a cardioactive steroid of formula: wherein R is the broken line indicates an optional 4, 5- double bond, and Y is oxo or a hydrogen atom with an α- or #-(hydroxy or C 1-6 acyloxy) group which may be α-oriented in the 4, 5 #-dihydro compounds only. Routes of administration are not specified. Reference has been directed by the Comptroller to Specification 1,184,238.

公开(公告)号：DK131788B

公开(公告)日：1975-09-01

申请号：DK569373

申请日：1973-10-19

Applicant: HOECHST AG

Inventor： STACHE U ,  RADSCHEIT K

IPC: C07J31/00 ,  C07D20060101 ,  C07J1/00 ,  C07J17/00 ,  C07J19/00 ,  C07J21/00

Abstract: The present invention relates to an improved process for the manufacture of beta -(3-oxo-7 alpha -thioacyl-17 beta -hydroxy-4-androsten-17 alpha -yl)-propionic acid gamma -lactones, in which a beta -(3-oxo-17 beta -hydroxy-4,6-androstadien-17 alpha -yl)-propionaldehyde dialkyl or alkylene acetal is reacted with a thiocarboxylic acid, in a mixture of water an an organic solvent miscible with water, to yield a beta -(3'-oxo-7' alpha -thioacyl-17 beta '-hydroxy-4'-androsten-17 alpha -yl)-propionaldehyde-dialkyl or alkylene acetal and in which this compound is oxidized in an acid solution to yield the corresponding gamma -lactone.