- Stereoselective gram-scale synthesis of (S)-5,5-dimethyl-4-phenyloxazolidin-2-one
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A stereoselective gram-scale synthesis of (S)-5,5-dimethyl-4-phenyloxazolidin-2-one, SuperQuat [(S)-1], is described. The key step is the diastereoselective reduction of (E)-imine (2), which is synthesized from 2-hydroxy-2-methylpropiophenone (4) and (S)-
- Sugiyama, Shigeo,Arai, Satoshi,Ishii, Keitaro
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- HYDROXAMIC ACID DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS
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The invention relates to a compound of formula (I): or a pharmaceutically acceptable salt thereof, thereof, wherein: G is a group of formula (II); and pharmaceutically acceptable salts, prodrugs, hydrates, or solvates, thereof, wherein A, B. L1-L4 A, B, R1-R4 and m are as defined herein. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and their use in treating a bacterial infection.
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Page/Page column 33-34
(2010/04/25)
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- Stereoselective functionalisation of SuperQuat enamides: asymmetric synthesis of homochiral 1,2-diols and α-benzyloxy carbonyl compounds
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Homochiral (E)- and (Z)-enamides derived from SuperQuat (S)-4-phenyl-5,5-dimethyl-oxazolidin-2-one undergo highly diastereoselective epoxidation upon treatment with dimethyldioxirane. Subsequent epoxide opening with meta-chlorobenzoic acid proceeds via a stereoselective SN1-type process, with retention of configuration, to give the corresponding 1′-m-chlorobenzoyl-2′-hydroxy derivatives. Treatment of the SuperQuat enamides with mCPBA effects this two-step transformation in one pot. Reductive cleavage of the isolated 1′-m-chlorobenzoyl-2′-hydroxy derivatives (≥96% de) generates homochiral 1,2-diols in ≥96% ee. Alternatively, regioselective lithiation of the enamide at C(1′) with tBuLi followed by reaction with an aromatic aldehyde and in situ O-benzylation generates a 1′-(benzyloxy-aryl-methyl) substituted enamide with high diastereoselectivity. Subsequent oxidative cleavage of the enamide C{double bond, long}C bond with NaIO4/RuCl3 followed by methanolysis of the resultant N-acyl fragment furnishes an O-benzyl protected α-hydroxy methyl ester in high ee.
- Aciro, Caroline,Davies, Stephen G.,Garner, A. Christopher,Ishii, Yutaka,Key, Min-Suk,Ling, Kenneth B.,Prasad, R. Shyam,Roberts, Paul M.,Rodriguez-Solla, Humberto,O'Leary-Steele, Catherine,Russell, Angela J.,Sanganee, Hitesh J.,Savory, Edward D.,Smith, Andrew D.,Thomson, James E.
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p. 9320 - 9344
(2008/12/22)
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- Kinetic resolution of 2-oxazolidinones via catalytic, enantioselective N-acylation
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Kinetic resolution of racemic 2-oxazolidinones via catalytic, enantioselective N-acylation has been achieved for the first time and with outstanding selectivities. Copyright
- Birman, Vladimir B.,Jiang, Hui,Li, Ximin,Guo, Lei,Uffman, Eric W.
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p. 6536 - 6537
(2007/10/03)
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- Oxidative functionalisation of superquat enamides: Asymmetric synthesis of homochiral 1,2 diols
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Homochiral (E)-enamides derived from (S)-4-phenyl-5,5-dimethyl-oxazolidin-2-one undergo highly diastereoselective epoxidation upon treatment with dimethyldioxirane (DMDO). Treatment with m-chloroperbenzoic acid (MCPBA) produces syn-(4S, 1′R,2′)-1′ -acyloxy-2′-hydroxy derivatives with high diastereoselectivity, consistent with a mechanism involving initial epoxidation and subsequent in situ SN1 type epoxide opening and trapping with m-chlorobenzoic acid. Reductive cleavage of the isolated 1′-acyloxy-2′-hydroxy derivatives generates 1,2-diols in high yields and in high ee.
- Davies, Stephen G.,Key, Min-Suk,Rodriguez-Solla, Humberto,Sanganee, Hitesh J.,Savory, Edward D.,Smith, Andrew D.
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p. 1659 - 1662
(2007/10/03)
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- SuperQuat N-acyl-5,5-dimethyloxazolidin-2-ones for the asymmetric synthesis of α-alkyl and β-alkyl aldehydes
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The proclivity of α-branched N-2′-benzyl-3′-phenylpropionyl derivatives of (S)-4-benzyl-5,5-dimethyl-, (S)-4-phenyl-5,5-dimethyl-, (S)-4-isopropyl-5,5-dimethyl-, (S)-4-benzyl- and (S)-4-benzyl-5,5-diphenyl-oxazolidin-2-ones to generate directly 2-benzyl-3-phenylpropionaldehyde upon hydride reduction with DIBAL is investigated. The (S)-4-benzyl-5,5-dimethyl-derivative proved optimal for inhibition of endocyclic nucleophilic attack, giving 2-benzyl-3-phenylpropionaldehyde in good yield upon reduction. Application of this methodology for the asymmetric synthesis of chiral aldehydes via diastereoselective enolate alkylation of a range of (S)-N-acyl-4-benzyl-5,5-dimethyloxazolidin-2-ones to afford an array of α-substituted-N-acyl-5,5-dimethyloxazolidin-2-ones (85-94% de) and subsequent reduction with DIBAL afforded directly non-racemic α-substituted aldehydes without loss of stereochemical integrity (87-94% ee). The extension of this protocol for the asymmetric synthesis of β-substituted aldehydes is demonstrated, via the diastereoselective conjugate addition of a range of organocuprates to (S)-N-acyl-4-phenyl-5,5-dimethyloxazolidin-2-ones which proceeds with high diastereoselectivity (generally >95% de). Reduction of the conjugate addition products with DIBAL gives non-racemic β-substituted aldehydes in high yields and in high ee (generally >95% ee). This methodology is exemplified by the asymmetric synthesis of (R)-3-isopropenylhept-6-enal, which has previously been used in the synthesis of (3Z,6R)-3-methyl-6-isopropenyl-3,9-decadien-1-yl acetate, a component of the sex pheromones of the California red scale.
- Bull, Steven D.,Davies, Stephen G.,Nicholson, Rebecca L.,Sanganee, Hitesh J.,Smith, Andrew D.
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p. 2886 - 2899
(2007/10/03)
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- The 'SuperQuat' (R)-4-phenyl-5,5-dimethyl oxazolidin-2-one as an effective chiral auxiliary for conjugate additions: Asymmetric synthesis of (-)-aplysillamide B.
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(R)-4-Phenyl-5,5-dimethyl-oxazolidin-2-one, readily available from D- phenylglycine, is shown to be an effective chiral auxiliary for stereoselective conjugate additions to attached α,β-unsaturated N-acyl moieties. Its utility is demonstrated by the asymmetric synthesis of the antifungal, antibacterial (-)-Aplysillamide B.
- Davies, Stephen G.,Sanganee, Hitesh J.,Szolcsanyi, Peter
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p. 3337 - 3354
(2007/10/03)
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- A practical procedure for the multigram synthesis of the SuperQuat chiral auxiliaries
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An efficient and simple synthesis of oxazolidin-2-one SuperQuat chiral auxiliaries is described which provides rapid access to multigram quantities of the auxiliaries.
- Bull, Steven D.,Davies, Stephen G.,Jones, Simon,Polywka, Mario E. C.,Shyam Prasad,Sanganee, Hitesh J.
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p. 519 - 521
(2007/10/03)
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- 4-Substituted-5,5-Dimethyl Oxazolidin-2-ones as Effective Chiral Auxiliaries for Enolate Alkylations and Michael Additions
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4-(Methyl, phenyl, benzyl, and i-propyl)-5,5-dimethyl-oxazolidin-2-ones, readily available from α-amino acids, are shown to be effective chiral auxiliaries for stereoselective enolate alkylations and conjugate additions of attached N-acyl moieties.
- Davies, Stephen G.,Sanganee, Hitesh J.
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p. 671 - 674
(2007/10/02)
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