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WO1994019366A1 - Synthese chimique de la squalamine - Google Patents

Synthese chimique de la squalamine Download PDF

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Publication number
WO1994019366A1
WO1994019366A1 PCT/US1994/001822 US9401822W WO9419366A1 WO 1994019366 A1 WO1994019366 A1 WO 1994019366A1 US 9401822 W US9401822 W US 9401822W WO 9419366 A1 WO9419366 A1 WO 9419366A1
Authority
WO
WIPO (PCT)
Prior art keywords
hydroxy
cholestane
ether
group
compound
Prior art date
Application number
PCT/US1994/001822
Other languages
English (en)
Other versions
WO1994019366B1 (fr
Inventor
Robert M. Moriarty
Liang Guo
Sudersan M. Tuladhar
Original Assignee
Magainin Pharmaceuticals Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Magainin Pharmaceuticals Inc. filed Critical Magainin Pharmaceuticals Inc.
Priority to AU63928/94A priority Critical patent/AU6392894A/en
Publication of WO1994019366A1 publication Critical patent/WO1994019366A1/fr
Publication of WO1994019366B1 publication Critical patent/WO1994019366B1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
    • C07J13/007—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 17 (20)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J21/005—Ketals
    • C07J21/006—Ketals at position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
    • C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
    • C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
    • C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
    • C07J7/002—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa not substituted in position 16
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton

Definitions

  • Sgualamlne is a novel aminosterol recently isolated from the dogfish shark / Sgualus acanthias (K. Moore, et al., Proc. Nat. Acad. Sci. USA £0:1354-1358,1993. This water soluble steroid exhibits potent bactericidal activity against both Gram-positive and Gram-negative bacteria.
  • sgualamlne is fungicidal and exhibits lytic activity against protozoa. The molecule was initially recovered as a natural product through extraction of several tissues of the Dogfish shark, including stomach, liver, gallbladder, and spleen. Its structure was determined by fast atom bombardment mass spectroscopy and NMR.
  • Figure 2 illustrates the synthesis of 3-oxo-7 ⁇ -hydroxy-24 £tert-butyldimethylsiloxy-5 ⁇ -cholestane (compound 13) from chenodeoxycholic acid described in Example 2.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)

Abstract

L'invention se rapporte à des procédés de préparation ou synthèse chimique de la squalamine, un antibiotique stérolique. On effectue de préférence la préparation en modifiant la position 3 d'une fonction alcool-5α-cholestane protégée par un 3-oxo-7α-hydroxy-24z-éther avec une fraction spermidino afin de former une fonction -5α-cholestane protégée par un 3β-spermidino-7α-hydroxy-24z-éther; en déprotégeant la position 24 de la fonction -5α-cholestane protégée par un 3β-spermidino-7α-hydroxy-24z-éther pour obtenir l'hydroxyle libre; et en sulfatant la position 24 du 3β-spermidino-7α, 24-dihydroxy-5α-cholestane.
PCT/US1994/001822 1993-02-26 1994-02-24 Synthese chimique de la squalamine WO1994019366A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU63928/94A AU6392894A (en) 1993-02-26 1994-02-24 Chemical synthesis of squalamine

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2334793A 1993-02-26 1993-02-26
US08/023,347 1993-02-26

Publications (2)

Publication Number Publication Date
WO1994019366A1 true WO1994019366A1 (fr) 1994-09-01
WO1994019366B1 WO1994019366B1 (fr) 1994-10-27

Family

ID=21814560

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1994/001822 WO1994019366A1 (fr) 1993-02-26 1994-02-24 Synthese chimique de la squalamine

Country Status (2)

Country Link
AU (1) AU6392894A (fr)
WO (1) WO1994019366A1 (fr)

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040728A3 (fr) * 1995-06-07 1997-03-27 Magainin Pharma Composes d'aminosterol utiles comme inhibiteurs de l'echangeur sodium/proton (nhe), methodes et compositions pharmaceutiques utilisant ces inhibiteurs, et procedes d'evaluation de l'efficacite inhibitrice du nhe desdits composes
US5693769A (en) * 1991-12-13 1997-12-02 Transcell Technologies, Inc. Glycosylated steroid derivatives for transport across biological membranes and process for making and using same
US5721226A (en) * 1993-03-10 1998-02-24 Magainin Pharmaceuticals Inc. Method for inhibiting angiogenesis using squalamine and squalamine steroid derivatives
US5763430A (en) * 1995-06-07 1998-06-09 Magainin Pharmaceuticals Inc. Method of treating a viral infection by administering a steroid compound
US5792635A (en) * 1995-06-07 1998-08-11 Magainin Pharmaceuticals, Inc. Method of inhibiting the sodium/proton exchanger NHE3 and method of inhibiting growth by administering squalamine
US5795870A (en) * 1991-12-13 1998-08-18 Trustees Of Princeton University Compositions and methods for cell transformation
US5795885A (en) * 1995-06-07 1998-08-18 Magainin Pharmaceuticals Inc. Method of inhibiting profileration of cells by administering an aminosterol compound
US5840936A (en) * 1995-06-07 1998-11-24 Magainin Pharmaceuticals Inc. Aminosterol compounds useful as inhibitors of the sodium/proton exchanger (NHE)
US5840740A (en) * 1995-06-07 1998-11-24 Magainin Pharmaceuticals Inc. Aminosterol compounds and a method of treating infection using the aminosterol compounds
US5847172A (en) * 1995-06-07 1998-12-08 Magainin Pharmaceuticals Inc. Certain aminosterol compounds and pharmaceutical compositions including these compounds
US5856535A (en) * 1994-08-18 1999-01-05 Magainin Pharmaceuticals, Inc. Aminosterol ester compounds
US5874597A (en) * 1995-06-07 1999-02-23 Magainin Pharmaceuticals, Inc. Certain aminosterol compounds and pharmaceutical compositions including these compounds
US5994336A (en) * 1995-06-07 1999-11-30 Magainin Pharmaceuticals Inc. Method of inhibiting proliferation of cells by administering an aminosterol compound
US6143738A (en) * 1995-06-07 2000-11-07 Magainin Pharmaceuticals, Inc. Therapeutic uses for an aminosterol compound
US6147060A (en) * 1996-04-26 2000-11-14 Magainin Pharmaceuticals Treatment of carcinomas using squalamine in combination with other anti-cancer agents
JP2001505207A (ja) * 1996-12-06 2001-04-17 マガイニン ファーマシューティカルズ インコーポレーテッド アミノステロール、ビタミンｄ類似体および他の化合物の製造に有用な２４−ヒドロキシル化された化合物の立体選択的合成
US6596712B2 (en) 1996-04-26 2003-07-22 Genaera Corporation Treatment of carcinomas using squalamine in combination with other anti-cancer agents or modalities
EP1325928A4 (fr) * 2000-09-08 2004-04-21 Kuraray Co Procode de preparation de derives de pregnane
US6933383B2 (en) 2000-04-12 2005-08-23 Genaera Corporation Regioselective and stereoselective oxidation of fused ring systems useful for the preparation of aminosterols
US7153988B2 (en) 2001-09-04 2006-12-26 Kuraray Co., Ltd. 7α-hydroxy-pregn-4-en-3-one-20-carbaldehyde, process for producing the same, and process for producing 7α, 21-dihydroxy-20-methyl-pregn-4-en-3-one from the same
WO2008110941A3 (fr) * 2007-03-14 2009-05-22 Univ Aix Marseille Ii Nouveau procédé de synthèse d'un précurseur de squalamine et/ou de trodusquemine
JP2015514781A (ja) * 2012-04-20 2015-05-21 オーエイチアール・ファーマシューティカル・インコーポレイテッドＯｈｒ Ｐｈａｒｍａｃｅｕｔｉｃａｌ，Ｉｎｃ． Ｐｔｐ１ｂ関連疾患の処置のためのアミノステロイド化合物
US10131688B2 (en) 2014-11-19 2018-11-20 NZP UK Limited 5.beta.-6-alkyl-7-hydroxy-3-one steroids as intermediates for the production of steroidal FXR modulators
US10301350B2 (en) 2014-11-19 2019-05-28 NZP UK Limited 6-alkyl-7-hydroxy-4-en-3-one steroids as intermediates for the production of steroidal FXR modulators
US10538550B2 (en) 2014-11-19 2020-01-21 NZP UK Limited 6.alpha.-alkyl-3,7-dione steroids as intermediates for the production of steroidal FXR modulators
US10597423B2 (en) 2014-11-19 2020-03-24 NZP UK Limited 6.alpha.-alkyl-6,7-dione steroids as intermediates for the production of steroidal FXR modulators
US10968250B2 (en) 2016-05-18 2021-04-06 NZP UK Limited Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid
CN116283604A (zh) * 2022-12-25 2023-06-23 苏州永健生物医药有限公司 一种亚精胺的制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993018773A1 (fr) * 1992-03-18 1993-09-30 The Children's Hospital Of Philadelphia Nouvel antibiotique d'aminosterol

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993018773A1 (fr) * 1992-03-18 1993-09-30 The Children's Hospital Of Philadelphia Nouvel antibiotique d'aminosterol

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
J. P. GUTHRIE: "A water soluble dimeric steroid with catalytic properties. Rate enhancements from hydrophobic binding", CANADIAN JOURNAL OF CHEMISTRY, vol. 64, no. 12, December 1986 (1986-12-01), OTTAWA CA, pages 2456 - 2469 *
K. S. MOORE ET AL: "Squalamine: an aminosterol antibiotic from the shark", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES USA, vol. 90, no. 4, 15 February 1993 (1993-02-15), WASHINGTON DC, USA, pages 1354 - 1358 *
M. DAVIS ET AL: "Steroid amines. Part IV. 3,17-Diaminoandrostane derivatives", JOURNAL OF THE CHEMICAL SOCIETY, no. 11, 1967, LETCHWORTH GB, pages 1045 - 1052 *

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5795870A (en) * 1991-12-13 1998-08-18 Trustees Of Princeton University Compositions and methods for cell transformation
US5693769A (en) * 1991-12-13 1997-12-02 Transcell Technologies, Inc. Glycosylated steroid derivatives for transport across biological membranes and process for making and using same
US5721226A (en) * 1993-03-10 1998-02-24 Magainin Pharmaceuticals Inc. Method for inhibiting angiogenesis using squalamine and squalamine steroid derivatives
US5733899A (en) * 1993-03-10 1998-03-31 Magainin Pharmaceuticals Inc. Method for treating infection using steroid based pharmaceutical compositions
US5856535A (en) * 1994-08-18 1999-01-05 Magainin Pharmaceuticals, Inc. Aminosterol ester compounds
US5840936A (en) * 1995-06-07 1998-11-24 Magainin Pharmaceuticals Inc. Aminosterol compounds useful as inhibitors of the sodium/proton exchanger (NHE)
US5792635A (en) * 1995-06-07 1998-08-11 Magainin Pharmaceuticals, Inc. Method of inhibiting the sodium/proton exchanger NHE3 and method of inhibiting growth by administering squalamine
US5795885A (en) * 1995-06-07 1998-08-18 Magainin Pharmaceuticals Inc. Method of inhibiting profileration of cells by administering an aminosterol compound
WO1996040728A3 (fr) * 1995-06-07 1997-03-27 Magainin Pharma Composes d'aminosterol utiles comme inhibiteurs de l'echangeur sodium/proton (nhe), methodes et compositions pharmaceutiques utilisant ces inhibiteurs, et procedes d'evaluation de l'efficacite inhibitrice du nhe desdits composes
US5840740A (en) * 1995-06-07 1998-11-24 Magainin Pharmaceuticals Inc. Aminosterol compounds and a method of treating infection using the aminosterol compounds
US5847172A (en) * 1995-06-07 1998-12-08 Magainin Pharmaceuticals Inc. Certain aminosterol compounds and pharmaceutical compositions including these compounds
US5763430A (en) * 1995-06-07 1998-06-09 Magainin Pharmaceuticals Inc. Method of treating a viral infection by administering a steroid compound
US5874597A (en) * 1995-06-07 1999-02-23 Magainin Pharmaceuticals, Inc. Certain aminosterol compounds and pharmaceutical compositions including these compounds
US5994336A (en) * 1995-06-07 1999-11-30 Magainin Pharmaceuticals Inc. Method of inhibiting proliferation of cells by administering an aminosterol compound
US6143738A (en) * 1995-06-07 2000-11-07 Magainin Pharmaceuticals, Inc. Therapeutic uses for an aminosterol compound
EP1420027A3 (fr) * 1995-06-07 2012-01-04 Genaera Corporation Composés d'aminostérol utiles comme inhibiteurs de l'échangeur sodium/proton (nhe), méthodes et compositions pharmaceutiques utilisant ces inhibiteurs, et procédés d'évaluation de l'efficacité inhibitrice du nhe desdits composés
US6596712B2 (en) 1996-04-26 2003-07-22 Genaera Corporation Treatment of carcinomas using squalamine in combination with other anti-cancer agents or modalities
US6147060A (en) * 1996-04-26 2000-11-14 Magainin Pharmaceuticals Treatment of carcinomas using squalamine in combination with other anti-cancer agents
US6262283B1 (en) 1996-12-06 2001-07-17 Magainin Pharmaceuticals Inc. Stereoselective synthesis of 24-hydroxylated compounds useful for the preparation of aminosterols, vitamin D analogs, and other compounds
JP2001505207A (ja) * 1996-12-06 2001-04-17 マガイニン ファーマシューティカルズ インコーポレーテッド アミノステロール、ビタミンｄ類似体および他の化合物の製造に有用な２４−ヒドロキシル化された化合物の立体選択的合成
US6610866B2 (en) 1996-12-06 2003-08-26 Magainin Pharmaceuticals, Inc. Stereoselective synthesis of 24-hydroxylated compounds useful for the preparation of aminosterols, vitamin D analogs, and other compounds
JP2009138000A (ja) * 1996-12-06 2009-06-25 Genaera Corp アミノステロール、ビタミンｄ類似体および他の化合物の製造に有用な２４−ヒドロキシル化された化合物の立体選択的合成
US6933383B2 (en) 2000-04-12 2005-08-23 Genaera Corporation Regioselective and stereoselective oxidation of fused ring systems useful for the preparation of aminosterols
US7728157B2 (en) 2000-04-12 2010-06-01 Ohr Pharmaceutical Inc. Regioselective and stereoselective oxidation of fused ring systems useful for the preparation of aminosterols
EP1325928A4 (fr) * 2000-09-08 2004-04-21 Kuraray Co Procode de preparation de derives de pregnane
US7153988B2 (en) 2001-09-04 2006-12-26 Kuraray Co., Ltd. 7α-hydroxy-pregn-4-en-3-one-20-carbaldehyde, process for producing the same, and process for producing 7α, 21-dihydroxy-20-methyl-pregn-4-en-3-one from the same
WO2008110941A3 (fr) * 2007-03-14 2009-05-22 Univ Aix Marseille Ii Nouveau procédé de synthèse d'un précurseur de squalamine et/ou de trodusquemine
JP2015514781A (ja) * 2012-04-20 2015-05-21 オーエイチアール・ファーマシューティカル・インコーポレイテッドＯｈｒ Ｐｈａｒｍａｃｅｕｔｉｃａｌ，Ｉｎｃ． Ｐｔｐ１ｂ関連疾患の処置のためのアミノステロイド化合物
US10556923B2 (en) 2012-04-20 2020-02-11 Ohr Pharmaceutical Inc. Aminosteroids for the treatment of a PTP1B associated disease
US11434257B2 (en) 2012-04-20 2022-09-06 Depymed Inc. Aminosteroids for the treatment of a PTP1B associated disease
US10131688B2 (en) 2014-11-19 2018-11-20 NZP UK Limited 5.beta.-6-alkyl-7-hydroxy-3-one steroids as intermediates for the production of steroidal FXR modulators
US10301350B2 (en) 2014-11-19 2019-05-28 NZP UK Limited 6-alkyl-7-hydroxy-4-en-3-one steroids as intermediates for the production of steroidal FXR modulators
US10538550B2 (en) 2014-11-19 2020-01-21 NZP UK Limited 6.alpha.-alkyl-3,7-dione steroids as intermediates for the production of steroidal FXR modulators
US10597423B2 (en) 2014-11-19 2020-03-24 NZP UK Limited 6.alpha.-alkyl-6,7-dione steroids as intermediates for the production of steroidal FXR modulators
US10968250B2 (en) 2016-05-18 2021-04-06 NZP UK Limited Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid
US11479577B2 (en) 2016-05-18 2022-10-25 NZP UK Limited Intermediates for the synthesis of bile acid derivatives, in particular of obeticholic acid
CN116283604A (zh) * 2022-12-25 2023-06-23 苏州永健生物医药有限公司 一种亚精胺的制备方法

Also Published As

Publication number Publication date
AU6392894A (en) 1994-09-14

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