- A steroid compound derivative having, its preparation process and its use in the preparation of Eplerenone
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The invention relates to a canrenone derivative steroid compound, a preparation method and an application in the medicine field, and particularly relates to 7alpha-nitro methyl-11alpha,17beta-dihydroxy-3-oxo-17alpha-pregna-4-ene-21-carboxylic acid-gamma-lactone (a compound shown in formula 2), a preparation method and an application in eplerenone preparation. The key steps of the invention are that nitromethane is used as a nucleophilic reagent; the alpha-nitro methyl group is introduced to the C-7 position stereoselectively so as to further construct a carboxylic acid methyl ester structure with a C-7alpha position configuration of eplerenone; the method of the invention has the characteristics of short steps, mild conditions, and low cost.
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- A diastereoselective synthesis of 7α-nitromethyl steroid derivative and its use for an efficient synthesis of eplerenone
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A novel and efficient method of stereoselectively introducing α-nitromethyl group to C-7 position of 11α-hydroxyl canrenone 4 was described. In addition, this method was successfully applied in a total synthesis of Eplerenone 8. The route was characteristic of simple operation, moderate reaction conditions with 5 steps and 55% total yield, at the same time, without any expensive or toxic reagent in use.
- Zhang, Bin,Chen, Hongli,Tang, Huanyu,Feng, Huijin,Li, Yuanchao
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p. 1086 - 1091
(2012/11/13)
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- A chemobiological synthesis of eplerenone
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This paper will describe an approach to the synthesis of eplerenone, which is being marketed for the treatment of hypertension. The synthesis begins with DHEA available from wild yams and uses a combination of microbiological and chemical transformations to build eplerenone. Georg Thieme Verlag Stuttgart.
- Wuts, Peter G. M.,Anderson, Andrew M.,Ashford, Scott W.,Goble, Michael P.,White, Michael J.,Beck, Doris,Gilbert, Ivan,Hrab
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p. 418 - 422
(2008/09/17)
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- PROCESS FOR PREPARING 7α-ALKOXYCARBONYL SUBSTITUTED STEROIDS
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Processes are described for the conversion of a steroid substrate having a 4,7-carbonyl bridge to a structure comprising a 7α-alkoxycarbonyl substituent by reaction of the substrate with an alkoxy group source, preferably in the presence of a base. Several optional process modifications are described. The reaction may be conducted at a temperature greater than about 70°C, with substantially shorter residence times than are required at lower temperatures. A saponification target may be incorporated into the reaction medium to consume free hydroxide compounds. The product 7α-alkoxycarbonyl compound may be recovered by crystallization, residual steroid values may be recovered from the crystallization mother liquor by extraction, and the extract may be processed to produce a repulp solution wherein the steroids may be re-equilibrated to produce additional 7α-alkoxycarbonyl substituted steroid product. Alternatively, the repulp solution may be recycled to a primary reactor wherein 4,7-carbonyl bridge substrate is converted to 7α-alkoxycarbonyl product. The process is particularly useful in the preparation of eplerenone, wherein a diketone intermediate comprising a 4,7-carbonyl bridge is reacted with an alkali metal methoxide to yield an 11α-hydroxy-7α-methoxycarbonyl compound (hydroxyester), the 11α-hydroxy group is converted to a leaving group which is then abstracted to produce a Δ-9,11 enester, and the enester is epoxidized to eplerenone. Also disclosed is an epoxidation reaction conducted at relatively low hydrogen peroxide to enester substrate ratio.
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Page/Page column 68-69
(2008/06/13)
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- Processes for preparing C-7 substituted steroids
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This invention relates to processes for the preparation of novel 7-carboxy substituted steroid compounds of Formula I,
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Page/Page column 4-6; 11-12
(2008/06/13)
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- Processes for preparation of 3-keto-7alpha-alkoxycarbonyl-delta-4,5- steroids and intermediates useful therein
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Multiple novel reaction schemes, novel process steps and novel intermediates are provided for the synthesis of epoxymexrenone and other compounds of Formula I wherein:-A-A- represents the group -CHR4-CHR5- or -CR4=CR5- R3, R4 and R5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano, varyloxy;R1 represents an alpha-oriented lower alkoxycarbonyl or hydroxyalkyl radical;-B-B- represents the group -CHR6-CHR7- or an alpha- or beta- oriented group: where R6 and R7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy; andR8 and R9 are independently selected from the group consisting of hydrogen, hydroxy, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy, or R8 and R9 together comprise a carbocyclic or heterocyclic ring structure, or R8 or R9 together with R6 or R7 comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring.
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