- Stereocontrolled functionalization of the diene system of compactin
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A facile regio- and stereo selective γ-functionlization of the 1,3-diene system of compactin via the key dienone 3 is described.
- Senanayake, Chris H.,Bill, Timothy J.,DiMichele, Lisa M.,Chen, Cheng Y.,Larsen, Robert D.,Verhoeven, Thomas R.,Reider, Paul J.
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- Bioprospecting lovastatin production from a novel producer Cunninghamella blakesleeana
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Beside anti-cholesterol activity, lovastatin garners worldwide attention for therapeutical application against various diseases especially cancer. A total of 36 filamentous fungi from soil samples were isolated and screened for lovastatin production by yeast growth bioassay method. C9 strain (later identified as Cunninghamella blakesleeana) was screened as potential strain of lovastatin production. Further confirmation of the compound was made using TLC, HPTLC and HPLC in which similar Rf value, densitogram peak and chromatogram peak against the standard lovastatin were observed, respectively. The purified lovastatin subjected for IR analysis showed a lactone ring peak at 1763.63?cm?1 similar to standard lovastatin. Further structural analysis including NMR and LC–MS of the purified lovastatin reassures the molecular formula and molecular weight similar to standard. In quantitative terms, C. blakesleeana, Aspergillus terreus and Aspergillus flavus produced 1.4?mg?g?1 DWS, 0.83?mg?g?1 DWS and 0.3?mg?g?1 DWS of lovastatin, respectively, (p 50: 145.9?μg?mL?1 (140?μL), and the percentage of inhibition is maximum at 199.5?μg/mL which is statistically significant (p 0.0001).
- Balraj, Janani,Jairaman, Karunyadevi,Kalieswaran, Vidhya,Jayaraman, Angayarkanni
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- Drug or Supplement Combination with Conjugated Linoleic Acid for Fat Loss in Mammals
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Food, feed or drug combinations with conjugated linoleic acid are described that cause enhanced fat loss in mammals more efficiently than any of the individual components of the combination. Food, feed, or drugs that activate AMP activated protein kinase, agonists of nuclear receptors that bind RXR in adipocytes, or statin inhibitors were found to be more effective for fat loss when combined with conjugated linoleic acid.
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- PROCESS FOR THE PURIFICATION OF LOVASTATIN
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The invention relates to a process for the preparation of lovastatin. More particularly, it relates to the preparation of lovastatin substantially free of dihydrolovastatin. The invention also relates to pharmaceutical compositions that include the lovastatin substantially free of dihydrolovastatin and use of said compositions for treating hypercholesterolemia.
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Page/Page column 5-8
(2008/06/13)
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- AN IMPROVED METHOD FOR MANUFACTURE OF 4-HYDROXY PYRAN-2-ONE DERIVATIVES
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A process for preparation of 4-hydroxy-pyran-2-one derivative of formula (I), wherein R is (a), and wherein R1 and R2 are methyl and R3 is hydrogen or methyl, comprising the steps of, heating a compound of formula (II), wherein R is as defined before, and R4 is hydrogen, NH4+ or an alkali metal, in a solvent mixture consisting of an aromatic hydrocarbon and a ketone in an inert atmosphere at a temperature of between 60°C to 92°C in the absence or presence of orthophosphoric acid or its alkali dihydrogen salts or alkali hydrogen salts of a dibasic acid, followed by optional neutralization of the reaction mixture with an organic base and obtaining compound of formula (I) in high purity and substantially free of impurities through a step of isolation and crystallization. The process leads to formation of derivatives of formula (I) in high purity with dimmer impurity (III) less than 0.1% and anhydro impurity (IV) below 0.15%.
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Page/Page column 27; 28
(2008/06/13)
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- LACTONIZATION PROCESS
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The instant invention discloses a process for preparation of compound of formula (II) comprising treatment of compound of formula (I) with sulphuric acid, wherein the sulphuric acid is added in one portion, at less than 0.8 equivalents of compound of formula (I); at a temperature less than -150 C; for a time less than 1 hour; in a water miscible solvent, preferably acetonitrile, where G = unsubstituted or substituted alkyl, aryl or hetero aryl and X = H or metal or amine.
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Page/Page column 9-10
(2008/06/13)
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- A METHOD FOR THE MANUFACTURE OF LOVASTATIN
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A method for the manufacture of Lovastatin of formula (I) is disclosed. The method comprises of: A. lactonisation of Mevinolinic acid (II) and isolation of impure Lovastatin (I), B. purification of impure Lovastatin (I), C. optionally, repurification of pure Lovastatin (I) from a mixture of alumina and a water miscible solvent.
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Page/Page column 17-18
(2008/06/13)
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- FED BATCH SOLID STATE FERMENTATION FOR THE PRODUCTION OF HMG-COA REDUCTASE INHIBITORS
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The present invention provides a novel method for producing compound of formula (I), its acid form or any salt form, where R1 is H or CH3, by solid state fermentation using fed-batch technique by culturing microorganisms capable of producing the compound of formula (I).
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Page 11 - 12
(2008/06/13)
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- Treatment of type 1 diabetes with PDE5 inhibitors
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The use of a PDE5 inhibitor without substantial PDE2 inhibiting activity, or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of Type 1 Diabetes. A method of treating Type 1 Diabetes in an individual suffering from Type 1 Diabetes, which method comprises administering to said individual an effective amount of a PDE5 inhibitor without substantial PDE2 inhibiting activity, or a pharmaceutically acceptable salt thereof.
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- Method for producing pharmaceutical dosage forms
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The invention relates to a method for producing a granulate while using spray-dried D-mannitol and to the production of pharmaceutical dosage forms comprised of granulates of this type. The invention additionally relates to granulates obtained by using this method and to pharmaceutical dosage forms, which contain statins, especially cerivastatin, and which can be produced from said granulates.
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- Highly purified simvastatin compositions
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The present invention relates to a process to prepare semi synthetic statins, to intermediates formed during said process and to highly purified simvastatin produced by the process.
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- Process for the production of semi synthetic statins via novel intermediates
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A process has been provided to produce semi synthetic statins, as for instance simvastatin with a high yield, for another statin, preferably a naturally occurring statin, as for instance lovastatin. Also a number of novel intermediate compounds, prepared during said process, has been provided.
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- Total synthesis of both (+)-compactin and (+)-mevinolin. A general strategy based on the use of a special titanium reagent for dicarbonyl coupling
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A strategy is described for stereocontrolled synthesis of hypocholesterolemic compounds, (+)-compactin and (+)-mevinolin, by an approach (Scheme II) based on 6, 7, 4-pentenal (9a), and (R)-3-methyl-4-pentenal (9b). The Evans asymmetric Diels-Alder technique was used (Scheme III) to prepare 13, which was converted into the cis ester 17. Chain extension, iodolactonization, and elimination of HI then gave optically pure 6. The homochiral epoxide 24, made (Scheme IV) from (S)-malic acid, was converted into 25 and then, by iodocarbonation, hydrolysis, and ketalization, into the iodo ketal 7. Evans asymmetric alkylation was used (Scheme V) to prepare 9b. Ozonolysis, ketalization, and reduction (LiAlH4) of 28 gave 31, which was transformed by Swern oxidation, Wittig methylenation, and acid hydrolysis into 9b. An optically pure intermediate (8), common to both syntheses, was assembled (Scheme VI) by alkylation of 6 with 7, reduction to a mixture of lactols, allylic oxidation, and decarbonylation. Aldol condensation (Scheme VII) of 8 with 4-pentenal, triethylsilylation, and ozonolysis gave the enone aldehydes 39, epimeric at C-1. A modified McMurry reaction requiring an excess of a reagent prepared from C8K and TiCl3 (2:1 molar ratio) in DME, produced the ethers 40, which were converted into (+)-compactin by appropriate modification of the oxygen functionality. The strategy is general and was applied with minor modifications (Scheme VIII) to the synthesis of (+)-mevinolin.
- Clive,Murthy,Wee,Prasad,Da Silva,Majewski,Anderson,Evans,Haugen,Heerze,Barrie
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p. 3018 - 3028
(2007/10/02)
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- Remote Diastereoselection in the Asymmetric Total Synthesis of Mevinolin
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The asymmetric total synthesis of mevinolin (1a) is described.The key diastereoselective processes used to parlay the lone stereogenic center of asymmetrically produced (S)-pulegone (2a) to mevinolin include orthoester-Claisen rearrangement of 2d to 3a, stereoselective iodolactonization of 3e to 4, Eschenmoser-Claisen rearrangement of 6 to 7a, stereoselective intramolecular ene reaction of 7b to 8, and a highly diastereoselective cyclocondesation of aldehyde 10 with Danishefsky's diene.The cyclocondensation reaction was found to be quite sensitive to the reactionconditions in which the use of TiCl4 produced a 90:10 mixture of 11/12 while MgBr2 gave a 22:78 mixture
- Wovkulich, P. M.,Tang, P. C.,Chadha, N. K.,Batcho, A. D.,Barrish, J. C.,Uskokovic, M. R.
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p. 2596 - 2599
(2007/10/02)
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- 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Inhibitors. 4. Side Chain Ester Derivatives of Mevinolin
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Modification of the 2(S)-methylbutyryl moiety of mevinolin led to a series of side chain ester derivatives.A systematic exploration of the structure-activity relationships showed that the introduction of an additional aliphatic group on the carbon α to the carbonyl group increased potency.This obsrevation led to the synthesis of compound 16, which has about 2.5 times the intrinsic inhibitory activity of mevinolin.
- Hoffman, W. F.,Alberts, A. W.,Anderson, P. S.,Chen, J. S.,Smith, R. L.,Willard, A. K.
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p. 849 - 852
(2007/10/02)
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- Process for 4a'(R),5'-dihydromevinolin
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Mevinolin is converted to its 4a',5'-dihydro derivative by a route involving protection of the 3',4'-double bond followed by reduction of the 4a',5'-double bond followed by deprotection of the 3',4'-positions.
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