A highly practicable synthesis of both enantiomers of 3-hydroxypipecolic acid derivatives 1, 2, 3, 4 is described. Screening of these molecules for glycosidase inhibition has been examined. Compound 3 was shown to be a potent inhibitor of beta-N-acetylglucosaminidase as well as Escherichia coli beta-glucuronidase.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2008.02.028DOI Listing

Publication Analysis

Top Keywords

3-hydroxypipecolic acid
8
synthesis stereoisomers
4
stereoisomers 3-hydroxypipecolic
4
acid 3-hydroxy-45-dehydropipecolic
4
3-hydroxy-45-dehydropipecolic acid
4
acid evaluation
4
evaluation glycosidase
4
glycosidase inhibitors
4
inhibitors highly
4
highly practicable
4

Similar Publications

Multidimensional engineering of Escherichia coli for efficient biosynthesis of cis-3-hydroxypipecolic acid.

Bioresour Technol

August 2023

Hangzhou Wahaha Group Co. Ltd., Hangzhou 310018, China; Hangzhou Wahaha Technology Co. Ltd., Hangzhou 310018, China; Key Laboratory of Food and Biological Engineering of Zhejiang Province, Hangzhou 310018, China. Electronic address:

Cis-3-hydroxypipecolic acid (cis-3-HyPip) is the crucial part of many alkaloids and drugs. However, its bio-based industrial production remains challenging. Here, lysine cyclodeaminase from Streptomyces malaysiensis (SmLCD) and pipecolic acid hydroxylase from Streptomyces sp.

View Article and Find Full Text PDF

R97 at "Handlebar" Binding Mode in Active Pocket Plays an Important Role in Fe(II)/α-Ketoglutaric Acid-Dependent Dioxygenase -P3H-Mediated Selective Synthesis of (2S,3R)-3-Hydroxypipecolic Acid.

Molecules

February 2023

Lab of Brewing Microbiology and Applied Enzymology, School of Biotechnology and Key Laboratory of Industrial Biotechnology of Ministry of Education, Jiangnan University, Wuxi 214122, China.

Pipecolic acid (Pip) and its derivative hydroxypipecolic acids, such as (2S,3R)-3-hydroxypipecolic acid (-3-L-HyPip), are components of many natural and synthetic bioactive molecules. Fe(II)/α-ketoglutaric acid (Fe(II)/2-OG)-dependent dioxygenases can catalyze the hydroxylation of pipecolic acid. However, the available enzymes with desired activity and selectivity are limited.

View Article and Find Full Text PDF

Designing of an Efficient Whole-Cell Biocatalyst System for Converting L-Lysine Into Cis-3-Hydroxypipecolic Acid.

Front Microbiol

June 2022

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China.

Cis-3-hydroxypipecolic acid (cis-3-HyPip), a key structural component of tetrapeptide antibiotic GE81112, which has attracted substantial attention for its broad antimicrobial properties and unique ability to inhibit bacterial translation initiation. In this study, a combined strategy to increase the productivity of cis-3-HyPip was investigated. First, combinatorial optimization of the ribosomal binding site (RBS) sequence was performed to tune the gene expression translation rates of the pathway enzymes.

View Article and Find Full Text PDF

Biosynthesis of cis-3-hydroxypipecolic acid from L-lysine using an in vivo dual-enzyme cascade.

Enzyme Microb Technol

March 2022

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, PR China.

Cis-3-Hydroxypipecolic acid (cis-3-HyPip) is an important intermediate for the synthesis of GE81112 tetrapeptides, a small family of unusual nonribosomal peptide congeners with potent inhibitory activity against prokaryotic translation initiation. In this study, we constructed a microbial cell factory that can convert L-lysine into cis-3-hydroxypipecolic acid (cis-3-HyPip). Lysine cyclodeaminase SpLCD and Fe(II)/α-ketoglutarate (2-OG)-based oxygenase GetF were co-expressed in Escherichia coli.

View Article and Find Full Text PDF

Total Synthesis and Structural Revision of the Antibiotic Tetrapeptide GE81112A.

Angew Chem Int Ed Engl

September 2018

R&D Therapeutic Area Infectious Diseases, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, 65926, Frankfurt am Main, Germany.

The total synthesis of the naturally occurring antibiotic GE81112A, a densely functionalized tetrapeptide, is reported. Comparison of spectral data with those of the natural product and the lack of biological activity of the synthesized compound led us to revise the published configuration of the 3-hydroxypipecolic acid moiety. This hypothesis was fully validated by the synthesis of the corresponding epimer.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!