Synthesis and glycosidase inhibitory activities of pyrrolidines and piperidines with N-(polyhydroxyalkyl) side chains

Sabrina Boutefnouchet, István Moldvai, E. Gács-Baitz, Claudia Bello, Pierre Vogel

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Amidification of L-proline (3) with (+)-(R,R)-6 and (-)-(S,S)-tartaric anhydride diacetate (7) gave N-substituted L-prohne derivatives 8a,b, respectively. Acids 8a,b were transformed into diesters 9a,b with MeOH/HCl. Similar reactions with methyl (2S,4R)-4 and (2R,4S)-4-acetoxypipecolate (5) led to bicyclic lactams 14a,b and 15a. Compounds 8a,b were converted into N-(trihydroxybutyl)pyrrolidine derivatives 8c,d, 10a,b and 11a,b. Methyl (2S,4R)-20a and (2R,4S)-4-acetoxy-N-[(2S,3S)-1,2,3-trihydroxybutyl]pipecolate (20b) were obtained by displacement of (-)-(2S,2S)-2-O-benzyl-3,4-O- isopropylidene-1-deoxy-1-iodothreitol (19) by 4 and 5. Compounds 20a,b were converted into (2S,4R,2′S,2′S)-21a and (2R,4S,2′S,3′S)- 4-hydroxy-2-hydromethyl-N-(2-benzyloxy-3,4-isopropylidenedioxy)piperidine (21b) and finally into unprotected pentols 22a,b. Nonprotected (2S,2′S, 3′S)-11a and (2S,2′R,3′R)-N-(1,2,3-trihydroxybutyl)prolinol (11b), as well as 22a,b, did not inhibit any of the 13 glycosidases assayed. However, a triacetoxy derivative, (2S,3S)-2,3-diacetoxy-4[(2R,4S)-4-acetoxy-2- (methoxycarbonyl)piperidin-1-yl]-4-oxobutanoic acid (13b) is an inhibitor (IC50 = 157 UM) of α-L-fucosidase from bovine kidney.

Original languageEnglish
Pages (from-to)3028-3037
Number of pages10
JournalEuropean Journal of Organic Chemistry
Issue number18
DOIs
Publication statusPublished - 2007

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Pyrrolidines
Piperidines
Glycoside Hydrolases
alpha-L-Fucosidase
Derivatives
Lactams
Acids
Anhydrides
Proline
Inhibitory Concentration 50
Kidney

Keywords

  • Alkaloids
  • Glycosides
  • Piperidines
  • Pyrrolidines

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis and glycosidase inhibitory activities of pyrrolidines and piperidines with N-(polyhydroxyalkyl) side chains. / Boutefnouchet, Sabrina; Moldvai, István; Gács-Baitz, E.; Bello, Claudia; Vogel, Pierre.

In: European Journal of Organic Chemistry, No. 18, 2007, p. 3028-3037.

Research output: Contribution to journalArticle

Boutefnouchet, Sabrina ; Moldvai, István ; Gács-Baitz, E. ; Bello, Claudia ; Vogel, Pierre. / Synthesis and glycosidase inhibitory activities of pyrrolidines and piperidines with N-(polyhydroxyalkyl) side chains. In: European Journal of Organic Chemistry. 2007 ; No. 18. pp. 3028-3037.
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abstract = "Amidification of L-proline (3) with (+)-(R,R)-6 and (-)-(S,S)-tartaric anhydride diacetate (7) gave N-substituted L-prohne derivatives 8a,b, respectively. Acids 8a,b were transformed into diesters 9a,b with MeOH/HCl. Similar reactions with methyl (2S,4R)-4 and (2R,4S)-4-acetoxypipecolate (5) led to bicyclic lactams 14a,b and 15a. Compounds 8a,b were converted into N-(trihydroxybutyl)pyrrolidine derivatives 8c,d, 10a,b and 11a,b. Methyl (2S,4R)-20a and (2R,4S)-4-acetoxy-N-[(2S,3S)-1,2,3-trihydroxybutyl]pipecolate (20b) were obtained by displacement of (-)-(2S,2S)-2-O-benzyl-3,4-O- isopropylidene-1-deoxy-1-iodothreitol (19) by 4 and 5. Compounds 20a,b were converted into (2S,4R,2′S,2′S)-21a and (2R,4S,2′S,3′S)- 4-hydroxy-2-hydromethyl-N-(2-benzyloxy-3,4-isopropylidenedioxy)piperidine (21b) and finally into unprotected pentols 22a,b. Nonprotected (2S,2′S, 3′S)-11a and (2S,2′R,3′R)-N-(1,2,3-trihydroxybutyl)prolinol (11b), as well as 22a,b, did not inhibit any of the 13 glycosidases assayed. However, a triacetoxy derivative, (2S,3S)-2,3-diacetoxy-4[(2R,4S)-4-acetoxy-2- (methoxycarbonyl)piperidin-1-yl]-4-oxobutanoic acid (13b) is an inhibitor (IC50 = 157 UM) of α-L-fucosidase from bovine kidney.",
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T1 - Synthesis and glycosidase inhibitory activities of pyrrolidines and piperidines with N-(polyhydroxyalkyl) side chains

AU - Boutefnouchet, Sabrina

AU - Moldvai, István

AU - Gács-Baitz, E.

AU - Bello, Claudia

AU - Vogel, Pierre

PY - 2007

Y1 - 2007

N2 - Amidification of L-proline (3) with (+)-(R,R)-6 and (-)-(S,S)-tartaric anhydride diacetate (7) gave N-substituted L-prohne derivatives 8a,b, respectively. Acids 8a,b were transformed into diesters 9a,b with MeOH/HCl. Similar reactions with methyl (2S,4R)-4 and (2R,4S)-4-acetoxypipecolate (5) led to bicyclic lactams 14a,b and 15a. Compounds 8a,b were converted into N-(trihydroxybutyl)pyrrolidine derivatives 8c,d, 10a,b and 11a,b. Methyl (2S,4R)-20a and (2R,4S)-4-acetoxy-N-[(2S,3S)-1,2,3-trihydroxybutyl]pipecolate (20b) were obtained by displacement of (-)-(2S,2S)-2-O-benzyl-3,4-O- isopropylidene-1-deoxy-1-iodothreitol (19) by 4 and 5. Compounds 20a,b were converted into (2S,4R,2′S,2′S)-21a and (2R,4S,2′S,3′S)- 4-hydroxy-2-hydromethyl-N-(2-benzyloxy-3,4-isopropylidenedioxy)piperidine (21b) and finally into unprotected pentols 22a,b. Nonprotected (2S,2′S, 3′S)-11a and (2S,2′R,3′R)-N-(1,2,3-trihydroxybutyl)prolinol (11b), as well as 22a,b, did not inhibit any of the 13 glycosidases assayed. However, a triacetoxy derivative, (2S,3S)-2,3-diacetoxy-4[(2R,4S)-4-acetoxy-2- (methoxycarbonyl)piperidin-1-yl]-4-oxobutanoic acid (13b) is an inhibitor (IC50 = 157 UM) of α-L-fucosidase from bovine kidney.

AB - Amidification of L-proline (3) with (+)-(R,R)-6 and (-)-(S,S)-tartaric anhydride diacetate (7) gave N-substituted L-prohne derivatives 8a,b, respectively. Acids 8a,b were transformed into diesters 9a,b with MeOH/HCl. Similar reactions with methyl (2S,4R)-4 and (2R,4S)-4-acetoxypipecolate (5) led to bicyclic lactams 14a,b and 15a. Compounds 8a,b were converted into N-(trihydroxybutyl)pyrrolidine derivatives 8c,d, 10a,b and 11a,b. Methyl (2S,4R)-20a and (2R,4S)-4-acetoxy-N-[(2S,3S)-1,2,3-trihydroxybutyl]pipecolate (20b) were obtained by displacement of (-)-(2S,2S)-2-O-benzyl-3,4-O- isopropylidene-1-deoxy-1-iodothreitol (19) by 4 and 5. Compounds 20a,b were converted into (2S,4R,2′S,2′S)-21a and (2R,4S,2′S,3′S)- 4-hydroxy-2-hydromethyl-N-(2-benzyloxy-3,4-isopropylidenedioxy)piperidine (21b) and finally into unprotected pentols 22a,b. Nonprotected (2S,2′S, 3′S)-11a and (2S,2′R,3′R)-N-(1,2,3-trihydroxybutyl)prolinol (11b), as well as 22a,b, did not inhibit any of the 13 glycosidases assayed. However, a triacetoxy derivative, (2S,3S)-2,3-diacetoxy-4[(2R,4S)-4-acetoxy-2- (methoxycarbonyl)piperidin-1-yl]-4-oxobutanoic acid (13b) is an inhibitor (IC50 = 157 UM) of α-L-fucosidase from bovine kidney.

KW - Alkaloids

KW - Glycosides

KW - Piperidines

KW - Pyrrolidines

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