Short syntheses of (S)-pipecolic acid, (R)-coniine, and (S)-δ-coniceine using biocatalytically-generated chiral building blocks

Tetrahedron Asymmetry

Volumn 9, Issue 11, 1998, Pages 1951-1965

  Sánchez Sancho, Francisco ^a   Herradón, Bernardo ^a  

^a INSTITUTO DE QUÍMICA ORGÁNICA GENERAL   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDASE; CONIINE; DELTA CONICEINE; N (TERT BUTOXYCARBONYL) 2 (HYDROXYMETHYL)PIPERIDINE; N BENZYLOXYCARBONYL 2 (HYDROXYMETHYL)PIPERIDINE; NATURAL PRODUCT; PIPECOLIC ACID; PIPERIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; ASPERGILLUS; CATALYSIS; CHIRALITY; DRUG SYNTHESIS; NONHUMAN; PRIORITY JOURNAL; REACTION ANALYSIS;

EID: 0032486418     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0957-4166(98)00178-5     Document Type: Article

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109. 22. Compounds (±)-5 and (±)-6 were prepared, in a nearly quantitative yield, from commercially available (±)-2-(hydroxymethyl)piperidine using standard procedures (see Experimental part).
110. 24
111. 24. Unless otherwise indicated, all the enantiomeric excesses were determined by capillary gas-liquid chromatography using cyclodextrin-based chiral stationary phases, which were prepared by Mrs. Ma Isabel Jiménez-Vacas (Centre de Química Organica, C. S. I. C.), to whom we thank for her assistance.
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114. (b) On the other hand, we have carried out some preliminary experiments on the hydrolysis of the esters (R)-9 and (R)-10 catalyzed by AA-I, both in buffer solution (pH 7) and in an acetone-containing buffer. The reactions are chemoselective, giving the alcohols of (R)-configuration [i.e.; (R)-5 and (R)-6, depending on the structure of the substrate]. Although the enantioselectivity of the hydrolysis was lower than the acylation, it allowed an entry to the enantiomers of the compounds reported in this paper (Faraldos, J.; Herradón, B. unpublished observations).
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116. 28. The enzyme acylase I from Aspergillus species (AA-I) was purchased from Aldrich or Sigma. Its specific activity is ca. 0.5 U/mg (as defined in the Sigma catalog: one unit can hydrolyze 1.0 mmol of N-acetyl-L-methionine per hour at pH 7.0 and 25°C). For the sake of uniformity, the amount of AA-I used in any experiment is indicated in units per mmol of substrate.
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119. 31. (a) It must be remembered that the theoretical yield of a kinetic resolution is 50%. (b) When the slow reacting enantiomer racemizes rapidly (Dynamic Kinetic Resolution), it is possible to get a higher yield than the theoretical one; for a recent overview, see: Caddick, S.; Jenkins, K. Chem. Soc. Rev. 1996, 25, 447-456.
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124. 24
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128. 1H-NMR spectrum of 13 is complex due to nitrogen inversion, we tentatively assigned the Z configuration to the double bond based in the coupling constant (J=12.4 Hz) of the olefinic protons.
129. 37. We have observed variable isolated yields of coniine (and hence its hydrochloride) and of δ-coniceine due to the high volatility of these alkaloids.
130. 38. Although we carried out a Wittig reaction of isolated aldehydes 11 and 12, it was more convenient to use the tandem Swern-Wittig reaction, without isolating the aldehydes (see Experimental part) [Ireland, R. E.; Norbeck, D. W. J. Org. Chem. 1985, 50, 2198-2200].
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