Enantioselective synthesis of (2R,4S)- and (2S,4R)-4-hydroxypipecolic acid from D-glucoheptono-1,4-lactone
Enantiomerically pure (2R,4S)-4-hydroxypipecolic acid [(+)-1] was synthesized from D-glucoheptono-1,4-lactone (2) via the 3,5-dideoxy-D-xylo- heptono-1,4-lactone (7). The latter was readily prepared by benzoylation of 2, followed by β-elimination and diastereoselective hydrogenation of the resulting...
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todo:paper_00223263_v64_n17_p6119_DiNardo2023-10-03T14:31:22Z Enantioselective synthesis of (2R,4S)- and (2S,4R)-4-hydroxypipecolic acid from D-glucoheptono-1,4-lactone Di Nardo, C. Varela, O. 3,5 dideoxy dextro xylo heptono 1,4 lactone 4 hydroxypipecolic acid dextro glucoheptono 1,4 lactone lactone derivative pipecolic acid derivative unclassified drug article drug synthesis enantiomer hydrogenation hydrolysis oxidation stereochemistry structure analysis Enantiomerically pure (2R,4S)-4-hydroxypipecolic acid [(+)-1] was synthesized from D-glucoheptono-1,4-lactone (2) via the 3,5-dideoxy-D-xylo- heptono-1,4-lactone (7). The latter was readily prepared by benzoylation of 2, followed by β-elimination and diastereoselective hydrogenation of the resulting furanones (4). Compound 7 was converted into the 6,7-O- cyclohexylidene derivative 11, which on treatment with tosyl chloride for long periods afforded the 2-chloro derivative 14, the precursor of the azide 15. Hydrogenolysis of 15 and protection of the amine gave the N- benzyloxycarbonyl derivative 19, having the required configuration for the stereocenters at C-2 and C-4. Removal of the cyclohexylidene group by hydrolysis and subsequent oxidative degradation of the resulting glycol system afforded the hexurono-6,3-lactone 21 as a key intermediate. Chemoselective reduction of the aldehyde function of 21 led to the alcohol 23, which was derivatized as the mesylate 24. Releasing of the amino group by hydrogenation, and dissolution of resulting 25 in aqueous alkali, promoted the intramolecular nucleophilic displacement of the mesylate to give (+)-1. Its enantiomer [(-)-1] was prepared by a similar sequence starting from 2. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00223263_v64_n17_p6119_DiNardo |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
3,5 dideoxy dextro xylo heptono 1,4 lactone 4 hydroxypipecolic acid dextro glucoheptono 1,4 lactone lactone derivative pipecolic acid derivative unclassified drug article drug synthesis enantiomer hydrogenation hydrolysis oxidation stereochemistry structure analysis |
| spellingShingle |
3,5 dideoxy dextro xylo heptono 1,4 lactone 4 hydroxypipecolic acid dextro glucoheptono 1,4 lactone lactone derivative pipecolic acid derivative unclassified drug article drug synthesis enantiomer hydrogenation hydrolysis oxidation stereochemistry structure analysis Di Nardo, C. Varela, O. Enantioselective synthesis of (2R,4S)- and (2S,4R)-4-hydroxypipecolic acid from D-glucoheptono-1,4-lactone |
| topic_facet |
3,5 dideoxy dextro xylo heptono 1,4 lactone 4 hydroxypipecolic acid dextro glucoheptono 1,4 lactone lactone derivative pipecolic acid derivative unclassified drug article drug synthesis enantiomer hydrogenation hydrolysis oxidation stereochemistry structure analysis |
| description |
Enantiomerically pure (2R,4S)-4-hydroxypipecolic acid [(+)-1] was synthesized from D-glucoheptono-1,4-lactone (2) via the 3,5-dideoxy-D-xylo- heptono-1,4-lactone (7). The latter was readily prepared by benzoylation of 2, followed by β-elimination and diastereoselective hydrogenation of the resulting furanones (4). Compound 7 was converted into the 6,7-O- cyclohexylidene derivative 11, which on treatment with tosyl chloride for long periods afforded the 2-chloro derivative 14, the precursor of the azide 15. Hydrogenolysis of 15 and protection of the amine gave the N- benzyloxycarbonyl derivative 19, having the required configuration for the stereocenters at C-2 and C-4. Removal of the cyclohexylidene group by hydrolysis and subsequent oxidative degradation of the resulting glycol system afforded the hexurono-6,3-lactone 21 as a key intermediate. Chemoselective reduction of the aldehyde function of 21 led to the alcohol 23, which was derivatized as the mesylate 24. Releasing of the amino group by hydrogenation, and dissolution of resulting 25 in aqueous alkali, promoted the intramolecular nucleophilic displacement of the mesylate to give (+)-1. Its enantiomer [(-)-1] was prepared by a similar sequence starting from 2. |
| format |
JOUR |
| author |
Di Nardo, C. Varela, O. |
| author_facet |
Di Nardo, C. Varela, O. |
| author_sort |
Di Nardo, C. |
| title |
Enantioselective synthesis of (2R,4S)- and (2S,4R)-4-hydroxypipecolic acid from D-glucoheptono-1,4-lactone |
| title_short |
Enantioselective synthesis of (2R,4S)- and (2S,4R)-4-hydroxypipecolic acid from D-glucoheptono-1,4-lactone |
| title_full |
Enantioselective synthesis of (2R,4S)- and (2S,4R)-4-hydroxypipecolic acid from D-glucoheptono-1,4-lactone |
| title_fullStr |
Enantioselective synthesis of (2R,4S)- and (2S,4R)-4-hydroxypipecolic acid from D-glucoheptono-1,4-lactone |
| title_full_unstemmed |
Enantioselective synthesis of (2R,4S)- and (2S,4R)-4-hydroxypipecolic acid from D-glucoheptono-1,4-lactone |
| title_sort |
enantioselective synthesis of (2r,4s)- and (2s,4r)-4-hydroxypipecolic acid from d-glucoheptono-1,4-lactone |
| url |
http://hdl.handle.net/20.500.12110/paper_00223263_v64_n17_p6119_DiNardo |
| work_keys_str_mv |
AT dinardoc enantioselectivesynthesisof2r4sand2s4r4hydroxypipecolicacidfromdglucoheptono14lactone AT varelao enantioselectivesynthesisof2r4sand2s4r4hydroxypipecolicacidfromdglucoheptono14lactone |
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