- Asymmetric synthesis of arylpropionic acids and aryloxy acids by using lactamides as chiral auxiliaries
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Two different dynamic kinetic resolution methods have been applied for the asymmetric synthesis of pharmaceutical arylpropionic acids and aryloxy acids by using amides of (S)-lactic acid as chiral auxiliaries. For arylpropionic acids the esterification mediated by dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP) proceeds with good asymmetric induction, while for aryloxyacetic acids the keystep is a diastereoselective substitution reaction in the presence of triethylamine and n-hexylammonium iodide as additives. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Ammazzalorso, Alessandra,Amoroso, Rosa,Bettoni, Giancarlo,De Filippis, Barbara,Fantacuzzi, Marialuigia,Giampietro, Letizia,Maccallini, Cristina,Tricca, Maria L.
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Read Online
- Stereoselective synthesis of 2-aryloxy acids from lactamide derived esters of racemic α-halo carboxylic acids
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Pyrrolidine derived (S)-lactamide auxiliaries mediate a highly stereoselective coupling reaction between racemic α-haloacids and aryloxides. These amide auxiliaries exhibit enhanced rates of reaction as well as increased degrees of diastereoselection over
- Devine, Paul N.,Dolling, Ulf -H.,Heid Jr., Richard M.,Tschaen, David M.
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Read Online
- Toward Chromanes by de Novo Construction of the Benzene Ring
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The work describes three principal Diels-Alder cycloaddition approaches toward chromanes that are designed for the de novo construction of the benzene ring. This study specifically focuses on the potential exploitation in the total synthesis of chromane-bearing natural products such as cebulactam A.
- Geist, Egor,Berneaud-K?tz, Helge,Baikstis, Tomas,Dr?ger, Gerald,Kirschning, Andreas
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supporting information
p. 8930 - 8933
(2019/11/14)
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- Efficient Stereoselective Synthesis of a Key Chiral Aldehyde Intermediate in the Synthesis of Picolinamide Fungicides
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A highly stereoselective and efficient synthesis of (4S,5S,6S)-6-(benzyloxy)-5-phenoxy-4-propoxyheptanal, a key intermediate for syntheses of picolinamide fungicides, is described in this report. The synthesis features a scalable allylpropyl ether preparation, an efficient synthesis of the C1-C3 anti,syn-(S,S,S) stereotriad via a highly diastereoselective allylboration, and Cu-catalyzed phenylation of a sterically hindered secondary alcohol with BiPh3(OAc)2 followed by highly regioselective hydroformylation with the formation of a linear aldehyde. Excellent overall route efficiency was achieved (six steps and 39% yield) starting from readily available and inexpensive (S)-ethyl lactate.
- Li, Fangzheng,Good, Steffen,Tulchinsky, Michael L.,Whiteker, Gregory T.
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p. 2253 - 2260
(2019/10/16)
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- A PROCESS FOR THE MANUFACTURE OF POSACONAZOLE
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The present invention discloses an improved process for the manufacture of Posaconazole, an anti-fungal agent belonging to the category of substituted Tetrahydrofuran Triazole compound. The present invention further describes preparation of formula A and formula B, the key intermediates in the preparation of Posaconazole. The invention also discloses novel intermediates that are useful in the synthesis of Posaconazole.
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Page/Page column 12; 14; 15
(2019/05/10)
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- Preparation method of posaconazole intermediate
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The invention discloses a preparation method of a key intermediate POB for preparing posaconazole. Firstly, BP004b04 and oxalic acid are salified to obtain POE; secondly, the POE reacts with di-tert-butyl dicarbonate in the presence of a base to obtain POP, and the POP is recrystallized; thirdly, the POP and POK react with each other in the presence of a base to obtain POR, and POS is obtained after a tert-butyl carbonate protecting group of the POR is removed; finally, the POS is subjected to ring closure to obtain the POB. By means of the method, in the obtained POB, the content of diastereomers is smaller than or equal to 0.01%, and the total yield of the entire route is high.
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Paragraph 0039; 0040; 0041; 0042; 0062; 0064-0066
(2019/06/30)
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- Preparation method of high-purity posaconazole
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The invention discloses a preparation method of posaconazole, comprising: subjecting BP004b04 and oxalic acid to salt forming to obtain POE; subjecting POE and di-tert-butyl decarbonate to reaction inthe presence of a base to obtain POP, and recrystallizing POP; subjecting POP and POK o reaction in the presence of a base to obtain POR, and removing tert-butyl carbonate protecting group from POR to obtain POS; subjecting the POS to ring closing to obtain POB; subjecting the POB and POA to reaction to obtain posaconazole. Posaconazole prepared via the preparation method has the content of diastereoisomers being /=0.01%, and the overall route has high total yield.
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Paragraph 0043; 0044; 0045; 0046; 0072; 0074; 0075; 0076
(2019/06/27)
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- Intermediate for preparing posaconazole
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The invention discloses an intermediate POP for preparing posaconazole. A structure of the intermediate is as shown in the specification. By using the intermediate to prepare POB, the obtained POB hasa diastereomer content being smaller than or equal to 0.01%, and the total yield of the overall route is relatively high.
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Paragraph 0040-0043; 0065; 0067-0068
(2019/07/04)
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- Total synthesis of (+)-herboxidiene/GEX 1A
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A total synthesis of (+)-herboxidiene/GEX 1A has been accomplished from (R)- and (S)-lactate esters in a highly efficient manner. Key steps of the synthesis involve substrate-controlled titanium-mediated aldol reactions from chiral lactate-derived ethyl ketones, an oxa-Michael cyclization, an Ireland-Claisen rearrangement, and a Suzuki coupling. Furthermore, computational studies of the oxa-Michael reaction have unveiled the dramatic influence of intramolecular hydrogen bonds on the stereochemical outcome of such cyclizations, whereas biological analyses have clearly proved the important cytoxicity of (+)-herboxidiene/GEX 1A.
- Gómez-Palomino, Alejandro,Pellicena, Miquel,Kr?mer, Katrina,Romea, Pedro,Urpí, Fèlix,Aullón, Gabriel,Padrón, José M.
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p. 1842 - 1862
(2017/03/09)
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- Total Synthesis and Absolute Configuration of Raputindole A
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The first total synthesis of the bisindole alkaloid raputindole A from the rutaceous plant Raputia simulans is reported. The key step is a Au(I)-catalyzed cyclization that assembles the cyclopenta[f]indole tricycle from a 6-alkynylated indoline precursor. The isobutenyl side chain was installed by Suzuki-Miyaura cross-coupling, followed by a regioselective reduction employing LiDBB. Starting from 6-iodoindole, the sequence needs nine steps and provided (±)-raputindole A in 6.6% overall yield. The absolute configuration of the natural product (+)-raputindole A was determined by quantum chemical calculation of the ECD spectrum.
- Kock, Mario,Jones, Peter G.,Lindel, Thomas
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supporting information
p. 6296 - 6299
(2017/12/08)
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- Compositions and methods for the treatment of metabolic syndrome
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The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of fo
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Page/Page column 25-26; 27
(2016/06/01)
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- Enantioselective synthesis of (-)-maoecrystal v by enantiodetermining C-H functionalization
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The evolution of a program directed at the enantioselective total synthesis of maoecrystal V, a highly modified ent-kauranoid, is described. An early stage chiral auxiliary-directed asymmetric C-H functionalization for the construction of a key benzofuran intermediate enabled the first asymmetric synthesis of the natural enantiomer of maoecrystal V, confirming the assigned stereochemistry. A divergent course of the central intramolecular Diels-Alder reaction, which is dependent on the nature of the dienophile, initially led to the development of an unanticipated and previously unknown isomer of maoecrystal V, which we named maoecrystal ZG. In light of the reported selective and potent cytotoxic activity of maoecrystal V, the cytotoxic properties of maoecrystal ZG were also investigated.
- Lu, Ping,Mailyan, Artur,Gu, Zhenhua,Guptill, David M.,Wang, Hengbin,Davies, Huw M. L.,Zakarian, Armen
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supporting information
p. 17738 - 17749
(2015/02/19)
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- Amides in one pot from Carboxylic Acids and Amines via Sulfinylamides
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An efficient method has been developed for the direct amidification of carboxylic acids via sulfinylamides preformed in situ by the reaction of pure amines with prop-2- ene-1-sulfinyl chloride. The method can be applied to aliphatic acids, including pivalic acid, aromatic acids, and primary and secondary amines. It is compatible with acids bearing unprotected alcohol, phenol, and ketone moieties and applicable to the synthesis of peptides. It does not induce their a-epimerization.
- Bai, Jianfei,Zambron, Bartosz K.,Vogel, Pierre
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supporting information
p. 604 - 607
(2014/04/03)
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF METABOLIC SYNDROME
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The invention relates to the compounds of formula (I) or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula (I), and methods for the treatment of metabolic syndrome may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of hyperuricemia, gout; dyslipidemia, obesity, urea cycle disorders, hyperglycemia, insulin resistance, diabetes mellitus, diabetes insipidus, type 1 diabetes, type 2 diabetes, microvascular complications,.macrovascular complications, lipid disorders, prediabetes., obesity, arrhythmia, myocardial infarction, stroke, neuropathy, renal complications, hypertriglyceridemia, cardiovascular complications, and post prandial hyperglycemia.
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Paragraph 0094; 0095
(2013/12/03)
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- Stereoselective titanium-mediated aldol reactions of α-benzyloxy methyl ketones
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Good levels of 1,4-anti asymmetric induction are obtained in the TiCl 3(i-PrO)-mediated aldol reaction of chiral α-benzyloxy methyl ketones with a wide array of aldehydes. This methodology represents a new approach to substrate-controlled acetate aldol reactions capable of providing highly functionalized fragments in a straightforward manner, which may be useful in the design of more efficient syntheses.
- Pellicena, Miquel,Solsona, Joan G.,Romea, Pedro,Urpi, Felix
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p. 10338 - 10350,13
(2012/12/12)
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- Stereoselective titanium-mediated aldol reactions of α-benzyloxy methyl ketones
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Good levels of 1,4-anti asymmetric induction are obtained in the TiCl 3(i-PrO)-mediated aldol reaction of chiral α-benzyloxy methyl ketones with a wide array of aldehydes. This methodology represents a new approach to substrate-controlled acetate aldol reactions capable of providing highly functionalized fragments in a straightforward manner, which may be useful in the design of more efficient syntheses.
- Pellicena, Miquel,Solsona, Joan G.,Romea, Pedro,Urpí, Fèlix
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p. 10338 - 10350
(2013/01/15)
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- Synthesis of β-amino alcohols via the reduction of lactamides derived from ethyl (2S)-lactate with borane-methyl sulfide
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Reactions of ethyl (2S)-lactate with various amines affords lactamides that are reduced with borane-methyl sulfide in the presence of boron trifluoride etherate to generate enantiomerically pure β-amino alcohols in good yield. Georg Thieme Verlag Stuttgart.
- Lewis, Frank W.,Eichler, Matthias C.,Grayson, David H.
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experimental part
p. 1923 - 1928
(2009/12/29)
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- FORUMLATIONS
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This invention relates to the use of lactamide compounds of formula (I): CH3CH(OH)C(=O)NR1R2, where R1 and R2 are each independently hydrogen; or C1-6 alkyl, C2-6 alkenyl or C3-6 cycloalkyl, each of which is optionally substituted by up to three substituents independently selected from phenyl, hydroxy, C1-5 alkoxy, morpholinyl and NR3R4 where R3 and R4 are each independently C1-3 alkyl; or phenyl optionally substituted by up to three substituents independently selected from C1-3 alkyl; or R1 and R2 together with the nitrogen atom to which they are attached form a morpholinyl, pyrrolidinyl, piperidinyl or azepanyl ring, each of which is optionally substituted by up to three substituents independently selected from C1-3 alkyl, in formulations to reduce the toxicity associated with other formulation components; to the use of certain lactamide compounds as solvents, especially in formulations, particularly in agrochemical formulations and in environmentally friendly formulations; to novel lactamide compounds; and to processes for preparing lactamide compounds.
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Page/Page column 5-6
(2009/09/25)
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- Process for the stereoselective preparation of (-)-halofenate and derivatives thereof
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The present invention provides a compounds the formula (IV): and methods for producing an α-(phenoxy)phenylacetic acid compound of the formula: wherein R1 is a member selected from the group consisting of: each R2 is a member indepen
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Page/Page column 12
(2008/06/13)
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- SUBSTITUTED ANILINIC PIPERIDINES AS MCH SELECTIVE ANTAGONISTS
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This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therepeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier.
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Page column 65; 66; 103; 104
(2010/02/06)
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- Simple and efficient preparation of enantiopure alkyl α-hydroxyalkyl ketones
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The acylation reaction of organolithium reagents with pyrrolidine-derived α-benzyloxy and α-silyloxy carboxamides provides a simple and high-yielding method for the preparation of enantiopure α-benzyloxy and α-silyloxy ketones.
- Ferrero,Galobardes,Martin,Montes,Romea,Rovira,Urpi,Vilarrasa
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p. 1608 - 1614
(2007/10/03)
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- Determination of the relative and absolute stereochemistry of a potent and α(1A)-selective adrenoceptor antagonist
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The binding affinities and selectivities of antagonists 1-4 for the α(1A)-adrenoceptor are dependent on the stereochemical orientation of the groups at the C-4 and C-5 positions of the oxazolidinone ring. The unambiguous assignment of the relative and abs
- Lagu, Bharat,Wetzel, John M.,Forray, Carlos,Patane, Michael A.,Bock, Mark G.
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p. 2705 - 2707
(2007/10/03)
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- A simple procedure for the preparation of enantiopure ethyl α-hydroxyalkyl ketones
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Amides derived from pyrrolidine and methyl (S)-lactate, methyl (S)-2-hydroxy-3-phenylpropanoate, or methyl (S)-2-hydroxy-3-methylbutanoate, after O-benzylation and O-silylation have been treated with EtLi or EtMgCl under suitable conditions, to give excellent overall yields of enantiopure ethyl ketones. The chelating ability of α-OBn amides (and even of α-O-TBS amides, which has been demonstrated by NMR to be better than that of N-OMe amides) accounts for the performance of the approach.
- Martin, Ricardo,Pascual, Oscar,Romea, Pedro,Rovira, Roser,Urpi, Felix,Vilarrasa, Jaume
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p. 1633 - 1636
(2007/10/03)
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- Kinetic resolution of aliphatic oxiranes mediated by in situ formed molydenum(VI) (oxo-diperoxo) hydroxy acid amide / chiral diol complexes
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In situ formed molybdenum(VI) (oxo-diperoxo) hydroxy acid amide / chiral diol complexes mediate the efficient kinetic resolution of simple aliphatic oxiranes.This method furnishes high enantiomeric yields of the residual oxirane.The oxidative cleavage of the oxiranes to carbonyl compounds is a non-stoichiometric reaction in the presence of oxygen. oxiranes / kinetic resolution / chiral molybdenum(VI) (oxo-diperoxo) complexes
- Schurig, Volker,Betschinger, Frank
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p. 555 - 560
(2007/10/02)
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