Nine of 16 Stereoisomeric Polyhydroxylated Proline Amides Are Potent 尾-N-Acetylhexosaminidase Inhibitors
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- 作者：Benjamin J. Ayers ; Andreas F. G. Glawar ; R. Fernando Mart铆nez ; Nigel Ngo ; Zilei Liu ; George W. J. Fleet ; Terry D. Butters ; Robert J. Nash ; Chu-Yi Yu ; Mark R. Wormald ; Shinpei Nakagawa ; Isao Adachi ; Atsushi Kato ; Sarah F. Jenkinson
- 刊名：Journal of Organic Chemistry
- 出版年：2014
- 出版时间：April 18, 2014
- 年：2014
- 卷：79
- 期：8
- 页码：3398-3409
- 全文大小：817K
- 年卷期：v.79,no.8(April 18, 2014)
- ISSN：1520-6904
文摘
All 16 stereoisomeric N-methyl 5-(hydroxymethyl)-3,4-dihydroxyproline amides have been synthesized from lactones accessible from the enantiomers of glucuronolactone. Nine stereoisomers, including all eight with a (3R)-hydroxyl configuration, are low to submicromolar inhibitors of 尾-N-acetylhexosaminidases. A structural correlation between the proline amides is found with the ADMDP-acetamide analogues bearing an acetamidomethylpyrrolidine motif. The proline amides are generally more potent than their ADMDP-acetamide equivalents. 尾-N-Acetylhexosaminidase inhibition by an azetidine ADMDP-acetamide analogue is compared to an azetidine carboxylic acid amide. None of the amides are good 伪-N-acetylgalactosaminidase inhibitors.