Isolation from Stevia rebaudiana of DMDP acetic acid, a novel iminosugar amino acid: synthesis and glycosidase inhibition profile of glycine and β-alanine pyrrolidine amino acids

Abstract

DMDP acetic acid [N-carboxymethyl-2,5-dideoxy-2,5-imino-d-mannitol] 5 from Stevia rebaudiana is the first isolated natural amino acid derived from iminosugars bearing an N-alkyl acid side chain; it is clear from GCMS studies that such derivatives with acetic and propionic acids are common in a broad range of plants including mulberry, Baphia, and English bluebells, but that they are very difficult to purify. Reaction of unprotected pyrrolidine iminosugars with aqueous glyoxal gives the corresponding N-acetic acids in very high yield; Michael addition of both pyrrolidine and piperidine iminosugars and that of polyhydroxylated prolines to tert-butyl acrylate give the corresponding N-propionic acids in which the amino group of β-alanine is incorporated into the heterocyclic ring. These easy syntheses allow the identification of this new class of amino acid in plant extracts and provide pure samples for biological evaluation. DMDP N-acetic and propionic acids are potent α-galactosidase inhibitors in contrast to potent β-galactosidase inhibition by DMDP.

Iminosugar idoBR1 Isolated from Cucumber Cucumis sativus Reduces Inflammatory Activity

“…7 While many iminosugars have been isolated from plants, BR1 (2S,3R,4R,5S)-3,4,5-trihydroxypiperidine-2-carboxylic acid (2) from Baphia racemosa 8,9 is one of the very few iminosugar acids that have been identified as a natural product. 10 Iminosugar acids are much more difficult to isolate and identify than their iminosugar analogues because of the high content of acidic and neutral amino acids in plants. idoBR1 was synthesized before it was isolated.…”

“…Certain varieties of cucumber have been shown to contain a single iminosugar amino acid, (2 R ,3 R ,4 R ,5 S )-3,4,5-trihydroxypiperidine-2-carboxylic acid (idoBR1), a trihydroxypipecolic acid ( 1 ) (Figure ). While many iminosugars have been isolated from plants, BR1 (2 S ,3 R ,4 R ,5 S )-3,4,5-trihydroxypiperidine-2-carboxylic acid ( 2 ) from Baphia racemosa , is one of the very few iminosugar acids that have been identified as a natural product . Iminosugar acids are much more difficult to isolate and identify than their iminosugar analogues because of the high content of acidic and neutral amino acids in plants.…”

The chemistry and biology of natural ribomimetics and related compounds

“… 72 Compared to DMDP (58), which showed strong inhibitory activity against β-galactosidases, DMDP N -acetic acid (63) is more active against α-galactosidases. 72 …”

Iminosugar Amino Acid idoBR1 Reduces Inflammatory Responses in Microglia

“…Of the very few iminosugar acids reported as natural products, BR1 (2 S ,3 R ,4 R ,5 S )-3,4,5-trihydroxypiperidine-2-carboxylic acid) ( 2 ), from the African tree Baphia racemosa , was the first to be isolated [ 10 ]. Iminosugar acids are much more difficult to isolate and identify than their iminosugar analogues, e.g., DNJ ( 3 ), due to the high content of acidic and neutral amino acids in plants [ 11 ] ( Scheme 1 ). idoBR1 ( 1 ), even though it was found in a common food plant, was synthesized before it was isolated [ 12 ].…”