Direct conversion of (1S,2S)-2-amino-1-[(4-methylthio)phenyl]-1,3-propanediol into its enantiomer for efficient synthesis of thiamphenicol and florfenicol

Giordano, Claudio; Cavicchioli, Silvia; Levi, Silvio; Villa, M.

doi:10.1021/jo00021a028

Cited by 37 publications

(11 citation statements)

References 2 publications

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“…6 There are in the literature numerous papers describing the racemic and asymmetric total syntheses of chloramphenicol and its derivatives, some of them published in the last five years. [7][8][9][10] Natural chloramphenicol and also its derivatives have two asymmetric centers with absolute configuration (R,R) and syn relative stereochemistry. Although showing decreased antibiotic properties, the racemic mixture is also biologically active, with the anti diastereoisomer being completely inactive.…”

Section: Introductionmentioning

confidence: 99%

“…The latter was then refluxed with methyl dichloroacetate to give racemic thiamphenicol (3) as the sole product in 65% yield (Scheme 5). Recently, Wu et al 10 have employed aminoalcohol 5 as the intermediate in the total synthesis of florfenicol, representing a formal synthesis of this antibiotic.All spectroscopic and physical data of thiamphenicol are completely compatible with those available in the literature and with that of a commercial sample. …”

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confidence: 99%

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An alternative approach to aminodiols from Baylis-Hillman adducts: stereoselective synthesis of chloramphenicol, fluoramphenicol and thiamphenicol

Mateus¹,

Coelho²

2005

J. Braz. Chem. Soc.

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Descrevemos aqui uma nova interpretação para a espectros de banda larga da síntese estereosseletiva de antibióticos de adutos Baylis-Hillman. A estrategia é baseada na preparação de um enocarbamato diretamente do aduto Baylis-Hillman, usando um rearranjo de Curtius. A hidroboração estereosseletiva fornece uma mistura de aminoalcools diasteroisomeros (syn e anti). Após separação cromatográfica, o diasteroisomero syn foi diretamente transformado no antibiótico.We describe herein a new approach for the stereoselective synthesis of broad spectrum antibiotics from Baylis-Hillman adducts. The strategy is based on the preparation of an ene-carbamate directly from a Baylis-Hillman adduct using a Curtius rearrangement reaction. Stereoselective hydroboration furnished a mixture of diastereoisomeric aminoalcohols (syn and anti). After chromatographic separation, the syn diastereoisomer was directly transformed into the antibiotics. Keywords: chloramphenicol, Baylis-Hillman, fluoramphenicol, thiamphenicol, -hydroxymethylketones IntroductionThe indiscriminate use of antibiotics in the Western World for the treatment of innumerous infectious diseases has caused as a principal consequence, the appearance of several microorganism species with drug multiresistance. 1 One of the most obvious strategies to overcome this problem is the utilization of more potent antibiotics but these can cause undesirable effects to patients. In the last few years some older antibiotics have being reintroduced as therapeutics for the treatment of infections caused by drug-multiresistant microorganisms. Among these antibiotics chloramphenicol and its derivatives appear as interesting alternatives.2 Due to toxicological problems, these antibiotics were banned from routine usage and their clinical use was restricted to some specific infectious diseases. Recently several papers 3 and patents 4 reported the utilization of chloramphenicol and its derivatives as valuable options for the treatment of some infectious disease with the toxicity of these drugs being under reinvestigation.Chloramphenicol is the first example of an antibiotic discovered through screening of soil microorganisms 5 and is also the only example of this class of therapeutical compound which was commercialized (Figure 1). 6 There are in the literature numerous papers describing the racemic and asymmetric total syntheses of chloramphenicol and its derivatives, some of them published in the last five years. [7][8][9][10] Natural chloramphenicol and also its derivatives have two asymmetric centers with absolute configuration (R,R) and syn relative stereochemistry. Although showing decreased antibiotic properties, the racemic mixture is also biologically active, with the anti diastereoisomer being completely inactive. 7 Recently our research group reported a strategy to prepare 2-amino-1,3-diols from Baylis-Hillman adducts, 11 which has permitted the synthesis of an oxazolidinone core which exhibited antibiotic properties. An adaptation of this strategy was used recently by us in the s...

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

An alternative approach to aminodiols from Baylis-Hillman adducts: stereoselective synthesis of chloramphenicol, fluoramphenicol and thiamphenicol

Mateus¹,

Coelho²

2005

J. Braz. Chem. Soc.

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“…However, as a consequence of both resolution methods the undesired enantiomer remains as waste, though for both methods laborious racamization protocols for the undesired enantiomer are described . Late in the resolution process, an elegant solution is described for the amino diol 3 by Giordano et al, who developed a process based on the inversion of both chiral centers of (1 S, 2 S )- 3 yielding the required (1 R, 2 R ) enantiomer. More recently, researchers at Celgene described the use of an aldolase to promote the retro-aldol reaction of the (2 R, 3 S ) enantiomer of racemic threo -3-[4-(methylthio)phenyl]serine ( 4 ), leaving the desired (2 S, 3 R ) enantiomer of 4 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 4-Sulfur-Substituted (2S,3R)-3-Phenylserines by Enzymatic Resolution. Enantiopure Precursors for Thiamphenicol and Florfenicol

Kaptein

Dooren

Boesten

et al. 1998

Org. Process Res. Dev.

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Enantiomerically pure 4-methylthio- and 4-methylsulfonyl-substituted (2S,3R)-3-phenylserines are prepared by enzymatic resolution of the corresponding racemic threo amides using the amidase from Ochrobactrum anthropi NCIMB 40321. The unwanted (2R,3S) enantiomers of the amides are separated from the enantiopure amino acids and easily racemized after Schiff base formation with the corresponding 4-(methylthio)- and 4-(methylsulfonyl)benzaldehyde. The racemization can be combined with the preparation of the racemic amides by aldol reaction under crystallization conditions to yield only the threo isomers. Enantiopure (2S,3R)-3-[4-(methylthio)phenyl]serine and (2S,3R)-3-[4-(methylsulfonyl)phenyl]serine are thus obtained in 78% and 62% overall yields starting from the corresponding substituted benzaldehydes. (2S,3R)-3-[4-(Methylthio)phenyl]serine is reduced to (1R,2R)-2-amino-1-[4-(methylthio)phenyl]propane-1,3-diol with NaBH4/H2SO4 and can be used for the synthesis of thiamphenicol and florfenicol.

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“…We showed previously that (1S,2S)-2-arylmethylamino-1-(4-nitrophenyl)-1,3-propanediols interact regioselectively with paraformaldehyde [1]. The first step of the method proposed for using the side product of the manufacture of the levomycetin analog thiamphenicol is based on the regioselectivity of the interaction of (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol with acetone [2].…”

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confidence: 99%

“…The use of this reaction [2] assumes a high degree of regioselectivity for it with the preferential formation of isomer 3, but there are no data in this work on the regioselectivity of the reaction. Meanwhile it is known that secondary alcoholic groups of 1,2-diols are more inclined than primary to form cyclic acetals [3].…”

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confidence: 99%

Regioselectivity of the interaction of (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol with some symmetrical ketones

Madesclaire

Coudert

Zaitsev

et al. 2004

Chem Heterocycl Compd

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Direct conversion of (1S,2S)-2-amino-1-[(4-methylthio)phenyl]-1,3-propanediol into its enantiomer for efficient synthesis of thiamphenicol and florfenicol

Cited by 37 publications

References 2 publications

An alternative approach to aminodiols from Baylis-Hillman adducts: stereoselective synthesis of chloramphenicol, fluoramphenicol and thiamphenicol

An alternative approach to aminodiols from Baylis-Hillman adducts: stereoselective synthesis of chloramphenicol, fluoramphenicol and thiamphenicol

Synthesis of 4-Sulfur-Substituted (2S,3R)-3-Phenylserines by Enzymatic Resolution. Enantiopure Precursors for Thiamphenicol and Florfenicol

Regioselectivity of the interaction of (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol with some symmetrical ketones

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