129145-37-5Relevant articles and documents
Development of a common fully stereocontrolled access to the medicinally important and promising prostacyclin analogues iloprost, 3-oxa-iloprost and cicaprost
Gais, Hans-Joachim,Kramp, Guido Johannes,Wolters, Dennis,Reddy, Leleti Rajender
, p. 5610 - 5617 (2006)
We describe new fully stereo-controlled syntheses of the prostacyclin analogues iloprost (2), the most active component of the drugs Ilomedin and Ventavis, and 3-oxa-iloprost (3), a derivative that is expected to have a significantly higher metabolic stability than 2 perhaps allowing an oral application. The syntheses are based on the same strategy and chiral bicyclic building block as used in the synthesis of cicaprost (4), the third most potent analogue that exhibits, besides prostacyclin-like activities, antimetastatic activities. Reaction of the enantiopure C6-C13 bicyclic aldehyde 17 with Cl 3CCOOH/Cl3CCOONa afforded trichlorocarbinol 24 which was converted via mesylate 25 to the C6-C14 bicyclic alkyne 9. The palladium-catalysed hydrostannylation of alkyne 9 gave with high regio- and stereoselectivity the alkenylstannane 26, Sn/Li exchange of which afforded the E-configured alkenyllithium derivative 8. Coupling of the C6-C14 building block 8 with the enantiopure C15-C20 building block, the N-methoxyamide 7, gave the C6-C20 bicyclic ketone 6 in high yield without epimerisation at C16. The configuration at C15 of iloprost (2) and 3-oxailoprost (3) was established through a highly diastereoselective reduction of ketone 6 with catecholborane and the chiral oxazaborolidine 28 which furnished alcohol (15S)-29. The highly stereoselective conversions of alcohol (15S)-29 to iloprost (2) and 3-oxa-iloprost (3), which include as key stereoselective steps an olefination with a chiral phosphonoacetate and a copper-mediated allylic alkylation, have already been described.
Conversion of Torgov's synthesis of estrone into a highly enantioselective and efficient process
Yeung, Ying-Yeung,Chein, Rong-Jie,Corey
, p. 10346 - 10347 (2007)
A very direct and efficient conversion of the achiral Torgov diketone into the natural form of O-methyl estrone is described. Copyright
Highly enantioselective oxazaborolidine-catalyzed reduction of 1,3-dicarbonyl compounds: Role of the additive diethylaniline
Chein,Yeung,Corey
supporting information; experimental part, p. 1611 - 1614 (2009/09/07)
The oxazaborolidine-catalyzed reduction of 2,2-disubstituted cycloalkan-1,3-diones or hindered 2,2-disubstituted cyclic ketones using catecholborane as reductant proceeds with greater enantioselectivity when N,N-diethylaniline is added. It has now been sh
EP4 receptor agonist, compositions and methods thereof
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Page/Page column 17, (2010/02/14)
This invention relates to potent selective agonists of the EP4 subtype of prostaglandin E2 receptors, their use or a formulation thereof in the treatment of glaucoma and other conditions, which are related to elevated intraocular pressure in the eye of a patient. This invention further relates to the use of the compounds of this invention for mediating the bone modeling and remodeling processes of the osteoblasts and osteoclasts.
Fully stereocontrolled total syntheses of the prostacyclin analogues 16S-iloprost and 16S-3-oxa-iloprost by a common route, using alkenylcopper-azoalkene conjugate addition, asymmetric olefination, and allylic alkylation
Kramp, Guido J.,Kim, Mikhail,Gais, Hans-Joachim,Vermeeren, Cornelia
, p. 17910 - 17920 (2007/10/03)
In this article we describe fully stereocontrolled total syntheses of 16S-iloprost (16S-2), the most active component of the drugs Ilomedin and Ventavis, and of 16S-3-oxa-iloprost (16S-3), a close analogue of 16S-2 having the potential for a high oral act
EP4 receptor agonist, compositions and methods thereof
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Page/Page column 16, (2010/02/08)
This invention relates to potent selective agonists of the EP4 subtype of prostaglandin E2 receptors, their use or a formulation thereof in the treatment of glaucoma and other conditions, which are related to elevated intraocular pressure in the eye of a patient. This invention further relates to the use of the compounds of this invention for mediating the bone modeling and remodeling processes of the osteoblasts and osteoclasts.
Asymmetric synthesis of complicated bicyclic and tricyclic polypropanoates via the double Diels-Alder addition of 2,2′-ethylidenebis[3,5-dimethylfuran]
Marchionni, Chiara,Vogel, Pierre
, p. 431 - 472 (2007/10/03)
A new, non-iterative method for the asymmetric synthesis of long-chain and polycyclic polypropanoate fragments starting from 2,2′-ethylidenebis[3,5-dimethylfuran] (2) has been developed. Diethyl (2E,5E)-4-oxohepra-2,5-dienoate (6) added to 2 to give a single meso-adduct 7 containing nine stereogenic centers. Its desymmetrization was realized by hydroboration with (+)-IpcBH2 (isopinocampheylborane), leading to diethyl (1S,2R,3S,4S,4aS,7R,8R,8aR,9aS,10R,10aR)-1,3,4,7,8,8a,9,9a-octahydro-3 -hydroxy-2,4,5,7,10-pentamethyl-9-oxo-2H-10H-2.4a:7.10a-diepoxyanthracene -1,8-dicarboxylate ((+)-8: 78% e.e.). Alternatively, 7 was converted to meso-(1R,2R,4R,4aR,5S,7S,8S,8aR,9aS,10s,10aS)-1,8-bis(acetoxymethyl) -1,8,8a,9a-tetrahydro-2,4,5,7,10-pentamethyl-2H-10H-2.4a:7.10a -diepoxyanthracene-3,6,9(4H,5H,7H)-trione (32) that was reduced enantioselectively by BH3 catalyzed by methyloxazaborolidine 19 derived from L-diphenylprolinol giving (1S,2S,4S,4aS,5S,6R,7R,8R,8aS,9aR,10R,10aS)-1,8-bis(acetoxymethyl) -1,8,8a,9a-tretrahydro-6-hydroxy-2,4,5,7,10-pentamethyl-2H,10H-2.4a:7.10a -diepoxyanthracene-3,9(4H,7H)-dione ((-)-33: 90% e.e.). Chemistry was explored to carry out chemoselective 7-oxabicyclo[2,2,1]heptanone oxa-ring openings and intra-ring C-C bond cleavage. Polycyclic polypropanoates such as (1R,2S,3R,4R,4aR,5S,6R,7S,8R,9R,10R,11S,12aR)-1-(ethoxycarbonyl) -1,3,4,7,9,10,11,12,12a-decahydro-3,11-dihydroxy-2,4,5,7,9-pentamethyl-12 -oxo-2H,5H-2,4a:6,9:6,11-triepoxybenzocyclodecene-10,8-carbolactone (51). (1S,2R,3R,4R,4aS,5S,7S,8R,9R,10R,12S,12aS)-1,10-bis(acetoxymethyl) tetradecahydro-8-(methoxymethoxy)-2,4,5,7,9-pentamethyl-3,9-bis ([2-(trimethylsilyl)ethoxy]methoxy)-6,11-epoxycyclodecene-4a,6,11,12-tetrol ((+)-83), and (1R,2R,3R,4aR,4bR,5S,6R,7R,8R,8aS,9S,10aR)-3,5-bis(acetoxymethyl) -4a,8a-dihydroxy-1-(methoxymethoxy)-2,6,8,9,10a-pentamethyl-2,7-bis ([2-(trimethysilsyl)ethoxy]methoxy)dodecahydrophenanthrene-4,10-dione (85) were obtained in few synthetic steps.
Chiral boron catalysts for reduction of ketones and process for their preparation
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, (2008/06/13)
The chiral catalyst of general structure 1, or its enantiomer STR1 is prepared by treating the corresponding N-carboxy anhydride of structure 2 STR2 with an aryl metal, especially a phenyl metal such as an aryl magnesium halide, aryl lithium, aryl zinc or
Preparation of some organo-bis(diisopropylamino)boranes and their application to the synthesis of oxazaborolidines
Chavant, P. Y.,Vaultier, M.
, p. 37 - 46 (2007/10/02)
The reactivity of ClB(NEt2)2 and ClB(NiPr2)2 towards organomagnesium or organolithium derivatives was studied.ClB(NiPr2)2 proved to be an excellent reagent for the preparation of pure boronic derivatives RB(NiPr2)2, which
Arylation process for preparation of chiral catalysts for ketone reduction
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, (2008/06/13)
The chiral catalyst of general structure 1, or its enantiomer STR1 is prepared by treating the corresponding N-carboxy anhydride of structure 2 STR2 with an aryl metal, especially a phenyl metal such as an aryl magnesium halide, aryl lithium, aryl zinc or