Synthesis and Antimetastatic Activity of l-Iduronic Acid-Type 1-N-Iminosugars

Abstract

L-Iduronic acid-type 1-N-iminosugars, (3R,4S,5R,6R)- and (3R,4S,5S,6R)-6-acetamido-4-amino-5-hydroxypiperidine-3-carboxylic acid (6 and 7, respectively), (3R,4S,5R,6R)-6-acetamido-4- guanidino-5-hydroxypiperidine-3-carboxylic acid (8), and (3R,4S,5R,6R)-4-amino- and -guanidino-5-hydroxy-6-(trifluoroacetamido) piperidine-3-carboxylic acid (9 and 10, respectively), were synthesized from siastatin B (1), isolated from Streptomyces culture, by the intramolecular Michael addition of O-imidate to its alpha,beta-unsaturated ester through cis oxiamination as a key step. Preincubation of B16 BL6 cells with these compounds inhibited invasion of the cells through reconstituted basement membranes. Pulmonary metastasis of B16 BL6 cells in mice was remarkably inhibited by pretreatment of the cells with these compounds in culture.

Gem-diamine 1-N-iminosugars as versatile glycomimetics: synthesis, biological activity and therapeutic potential

“…Molecular modeling using PM3 in MOPAC shows the structural similarity between a-L-iduronic acid and 119 (Figure 7). 29 As shown in Figure 7, 119 superimposes well on a-L-iduronic acid and the acetamido and guanidino moieties of 119 are also topographically equivalent to the hydroxyl moieties of a-L-iduronic acid.…”

“…28,29 The intramolecular Michael addition of O-imidate to the a,b-unsaturated ester through cis oxiamination 30 (Overman rearrangement, 110-111) as a key step effectively yielded L-uronic acid-type gem-diamine 1-N-iminosugars (Schemes 9 and 10). The a,b-unsaturated ester 110 readily available from siastatin B (1) smoothly underwent cis oxiamination through the conjugate addition of the intermediate imidate anion to result in the desired oxazoline 111 in a good yield and a trace amount of its epimer.…”

Present Status in the Chemistry of Hexuronic Acids Found in Glycosaminoglycans and their Mimetic Aza-Sugars Analogues

“…Bols et al reported the synthesis of isofagomine where a nitrogen atom is located at the anomeric position [48]. gem-Diamine 1-N-iminosugars are cyclic mono-saccharides with a nitrogen atom in place of the anomeric carbon [51]. These 1-N -iminosugars represented a glycosidase and glycosyltransferase inhibitors and served as useful tools to study the biological function of glycolipids and as chemotherapeutic agents.…”

“…L-Iduronic acid is a typical component of glycosaminoglycans (GAGs), where it plays an important role in various biological processes [4] . The new type of 1-N-iminosugars represented a glycosidase and glycosyltransferase inhibitors and served as useful tools to study the biological function of glycolipids and as chemotherapeutic agents [7]. Preparation of L-iduronic acid derivatives is much more complicated than that of glucuronic acid derivatives since neither L-iduronic acid nor L-idose are available as starting materials.…”

Stereospecific synthesis of N-tosyl derivatives of dihydroconduramine E-2 and ent-F-2

“…[1][2][3][4] The possibility of modifying or blocking these processes using glycosidaseinhibiting sugar mimics for biological and therapeutic applications has attracted much attention, 5,6 especially in relation to cancer, 7,8 viral infection, 9,10 genetic disorders, 11-13 diabetes 14 and obesity. 15 The biomedical and biotechnological applications of glycosidase-inhibiting sugar mimics have been reviewed.…”