Article ID Journal Published Year Pages File Type
1345066 Tetrahedron: Asymmetry 2008 11 Pages PDF
Abstract

Both enantiomerically pure antipodes of GABA analogues were prepared as hydrochloride salts, by enzymatic kinetic resolution of their precursors ethyl 2-(nitromethyl)alkanoates. These latter compounds can be easily transformed into enantiomerically pure 2-alkylsuccinic acids by a Nef reaction followed by oxidation. Interestingly, this reaction was particularly easy for the neopentyl derivative (S)-(+)-7d, which underwent conversion into its corresponding succinic acid derivative (S)-(−)-8d in buffered solution. The absolute configurations of the main compounds of interest involved are given, together with their CD spectra.

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Ethyl (R)-(−)-3-nitromethylheptanoateC10H19NO4Ee >99%[α]D25=-7.0 (c 0.35, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

Ethyl (R)-(−)-5-methyl-3-nitromethylhexanoateC10H19NO4Ee >99%[α]D = −6.5 (c 0.95, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

Ethyl (R)-(−)-3-nitromethyloctanoateC11H21NO4Ee >99.9%[α]D = −8.8 (c 0.25, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

Ethyl (R)-(−)-5,5-dimethyl-3-nitromethylhexanoateC11H21NO4Ee = 95%[α]D = −6.8 (c 0.5, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

Ethyl (R)-(−)-3-nitromethyl-4-phenylbutanoateC13H17NO4Ee = 94%[α]D = −11 (c 0.7, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(S)-(+)-3-Nitromethylheptanoic acidC8H15NO4Ee = 87%[α]D = +9.2 (c 0.5, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(S)-(+)-4-Methyl-3-nitromethylhexanoic acidC8H15NO4Ee = 92%[α]D = +6.0 (c 1.0, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(S)-(+)-3-Nitromethyloctanoic acidC9H17NO4Ee = 94%[α]D = +11.4 (c 0.5, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(S)-(+)-5,5-Dimethyl-3-nitromethylhexanoic acidC9H17NO4Ee = 65%[α]D = +4.0 (c 0.1, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(R)-(−)-3-Nitromethyl-4-phenylbutanoic acidC9H17NO4Ee = 94%[α]D = −11.0 (c 0.7, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(S)-(−)-2-Butylbutanedioic acidC7H14O4Ee = 87%[α]D = −24 (c 0.85, EtOH)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(S)-(−)-2-(2-Methylpropyl)butanedioic acidC7H14O4Ee = 92%[α]D = −24.0 (c 1.0, EtOH)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(S)-(−)-2-Pentylbutanedioic acidC8H16O4Ee = 94%[α]D = −22.1 (c 1.1, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(S)-(−)-2-(2,2-Dimethyl)propylbutanedioic acidC10H18O4Ee = 65%[α]D = −12.0 (c 0.45, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(R)-(+)-2-(Phenylmethyl)butandioic acidC11H12O4Ee = 94%[α]D = +24.0 (c 3.1, AcOEt)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-(−)-3-Aminomethylheptanoic acid hydrochlorideC8H18NO2ClEe >99%[α]D = −5.0 (c 0.45, H2O)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-(−)-3-Aminomethyl-5-methylhexanoic acid hydrochlorideC8H18NO2ClEe >99.9%[α]D = −10.5 (c 1, H2O)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-(−)-3-Aminomethyloctanoic acid hydrochlorideC9H20NO2ClEe >99%[α]D = −3.3 (c 1, H2O)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-(−)-3-Aminomethyl-5,5-dimethylhexanoic acid hydrochlorideC9H20NO2ClEe = 95%[α]D = −9.7(c 1, H2O)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-(−)-3-Aminomethyl-4-phenylbutanoic acid hydrochlorideC11H16NO2ClEe = 94%[α]D = −6.4 (c 1.45, H2O)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-(+)-4-Butyl-2-pyrrolidinoneC8H14NOEe >99%[α]D = +4.0 (c 0.25, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-(+)-4-Isobutyl-2-pyrrolidinoneC8H14NOEe >99%[α]D = +2.1 (c 0.5, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-(+)-4-Pentyl-2-pyrrolidinoneC9H16NOEe >99%[α]D = +3.1 (c 0.85, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-(−)-4-Neopentyl-2-pyrrolidinoneC9H16NOEe = 95%[α]D = −7.2 (c 0.75, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(R)-(−)-4-Benzyl-2-pyrrolidinoneC11H12NOEe = 94%[α]D = −5.1 (c 0.5, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

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Physical Sciences and Engineering Chemistry Inorganic Chemistry
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