WO2008091686A3 - SYNTHESIS OF 1α-FLUORO-25-HYDROXY-16-23E-DIENE-26,27-BISHOMO-20-EPI-CHOLECALCIFEROL - Google Patents

SYNTHESIS OF 1α-FLUORO-25-HYDROXY-16-23E-DIENE-26,27-BISHOMO-20-EPI-CHOLECALCIFEROL Download PDF

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Publication number
WO2008091686A3
WO2008091686A3 PCT/US2008/000970 US2008000970W WO2008091686A3 WO 2008091686 A3 WO2008091686 A3 WO 2008091686A3 US 2008000970 W US2008000970 W US 2008000970W WO 2008091686 A3 WO2008091686 A3 WO 2008091686A3
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WO
WIPO (PCT)
Prior art keywords
bishomo
cholecalciferol
epi
diene
fluoro
Prior art date
Application number
PCT/US2008/000970
Other languages
French (fr)
Other versions
WO2008091686A2 (en
Inventor
Hubert Maehr
Milan R Uskokovic
Original Assignee
Bioxell Spa
Hubert Maehr
Milan R Uskokovic
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 Bioxell Spa, Hubert Maehr, Milan R Uskokovic filed Critical Bioxell Spa
Priority to CA002676512A priority Critical patent/CA2676512A1/en
Publication of WO2008091686A2 publication Critical patent/WO2008091686A2/en
Publication of WO2008091686A3 publication Critical patent/WO2008091686A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C401/00—Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/48—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by oxidation reactions with formation of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/63—Esters of sulfonic acids
    • C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
    • C07C45/516—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of nitrogen-containing compounds to >C = O groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/29—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of oxygen-containing functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/293—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/297—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/013—Esters of alcohols having the esterified hydroxy group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/14—All rings being cycloaliphatic
    • C07C2602/24—All rings being cycloaliphatic the ring system containing nine carbon atoms, e.g. perhydroindane
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/14—All rings being cycloaliphatic
    • C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms
    • C07C2602/28—Hydrogenated naphthalenes

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention provides a method of producing 20-methyl vitamin D3 compounds of formula (I). The method includes hydroxylation, carbonyl reduction, fluoride substitution, epoxide deoxygenation, and Wittig-type couplings.
PCT/US2008/000970 2007-01-25 2008-01-25 SYNTHESIS OF 1α-FLUORO-25-HYDROXY-16-23E-DIENE-26,27-BISHOMO-20-EPI-CHOLECALCIFEROL WO2008091686A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA002676512A CA2676512A1 (en) 2007-01-25 2008-01-25 Synthesis of 1.alpha.-fluoro-25-hydroxy-16-23e-diene-26,27-bishomo-20-epi-cholecalciferol

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US89760907P 2007-01-25 2007-01-25
US60/897,609 2007-01-25

Publications (2)

Publication Number Publication Date
WO2008091686A2 WO2008091686A2 (en) 2008-07-31
WO2008091686A3 true WO2008091686A3 (en) 2008-10-09

Family

ID=39645084

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/000970 WO2008091686A2 (en) 2007-01-25 2008-01-25 SYNTHESIS OF 1α-FLUORO-25-HYDROXY-16-23E-DIENE-26,27-BISHOMO-20-EPI-CHOLECALCIFEROL

Country Status (3)

Country Link
CA (1) CA2676512A1 (en)
TW (1) TW200838544A (en)
WO (1) WO2008091686A2 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0808833A2 (en) * 1996-05-23 1997-11-26 F. Hoffmann-La Roche Ag Vitamin D3 analogs
WO1999003828A1 (en) * 1997-07-17 1999-01-28 F.Hoffmann-La Roche Ag Dihomo-seco-cholestanes with two unsaturated bones in the side chain
EP0957098A1 (en) * 1998-05-14 1999-11-17 F. Hoffmann-La Roche Ag Intermediates for the synthesis of 3-epi vitamin D3 metabolites and analogs
US20060111321A1 (en) * 2004-11-22 2006-05-25 Deluca Hector F 2-Methylene-19-nor-1alpha-hydroxy-17-ene-homopregnacalciferol and its uses

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0808833A2 (en) * 1996-05-23 1997-11-26 F. Hoffmann-La Roche Ag Vitamin D3 analogs
WO1999003828A1 (en) * 1997-07-17 1999-01-28 F.Hoffmann-La Roche Ag Dihomo-seco-cholestanes with two unsaturated bones in the side chain
EP0957098A1 (en) * 1998-05-14 1999-11-17 F. Hoffmann-La Roche Ag Intermediates for the synthesis of 3-epi vitamin D3 metabolites and analogs
US20060111321A1 (en) * 2004-11-22 2006-05-25 Deluca Hector F 2-Methylene-19-nor-1alpha-hydroxy-17-ene-homopregnacalciferol and its uses

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BLAEHR ET AL.: "Synthesis of Novel Hapten Derivatives of 1alpha,25-Dihydroxy-vitamin D3 and Its 20-Epi Analogue", J. ORG. CHEM., vol. 68, 2003, pages 1367 - 1375, XP008117906 *
FERRABOSCHI ET AL.: "Preparation of an A-ring building block for the total synthesis of 1alpha,25-dihydroxy vitamin D3 and structurally related congeners: lipase-catalyzed stereoselective esterification of a suitable epoxyalchol", TETRAHEDRON: ASYMMETRY, vol. 11, 2000, pages 2665 - 2668, XP004228717 *
KABAT ET AL.: "Efficient Synthesis of 1alpha-Fluoro A-Ring Phosphine Oxide, a Useful Building Block for Vitamin D Analogues, from (S)-Carvone via a Highly Selective Palladium-Catalyzed Isomerization of Dieneoxide to Dieneol", J. ORG. CHEM., vol. 66, 2001, pages 6141 - 6150, XP008118787 *

Also Published As

Publication number Publication date
TW200838544A (en) 2008-10-01
WO2008091686A2 (en) 2008-07-31
CA2676512A1 (en) 2008-07-31

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