Michel Trumtel

Triflic Anhydride: An Alternative Promoter in Glycosidations

Abstract The activation of glucosyl halides, trichloroacetimidates and of thioglucosides with triflic anhydride has been investigated showing that triflic anhydride promotes glycos idations with trichloracetimidates as well as with fluorides. There is also some potential for the activation of reactive thioglycosides. The role of triflic anhydride as a Lewis acid is likely.

The heparin-like antiproliferative activity of sulfated tetrasaccharides is sensitive to structural variation

Abstract The sulfated tetrasaccharide β-maltosyl-(1→4)-α,α-trehalose 2 with high antiproliferative activity on smooth muscle cells was modified in the maltosyl moiety by linking eight different disaccharides equatorially to trehalose; the biological activity varied strongly between different structures.

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes

ABSTRACT The four derivatives of β-maltosyl-(1→4)-trehalose have been synthesized, which are monodeoxygenated at the site of one of the primary hydroxyl groups. The tetrasaccharides were constructed in [2+2] block syntheses. Thus, 6′″-deoxy-β-maltosyl-(1→4)-trehalose was prepared by selective iodination of allyl 2,3,6,2′,3′-penta-O-acetyl-β-maltoside (3) followed by catalytic hydrogenolysis and coupling with 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (9), and 6″-deoxy-β-maltosyl-(1→4)-trehalose by selective iodination of allyl 4′,6′-O-isopropylidene-β-maltoside (14), coupling with 9, and one-step hydrogenolysis at the tetrasaccharide level. For the synthesis of 6′-deoxy-β-maltosyl-(1→4)-trehalose, the diol 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′-di-O-benzyl-α-D-glucopyranoside (22) was selectively iodinated and glycosylated with acetobromomaltose followed by catalytic hydrogenolysis. The 6-deoxy-β-maltosyl-(1→4)-trehalose was obtained ...

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes. II. the Synthesis of the 4- and 4′″-Monodeoxygenated Analogues

ABSTRACT Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at positions 4 or 4′″ have been synthesized in [2+2] block syntheses. After the preparation of precursors with only one free hydroxyl group the deoxy function was introduced by a Barton-McCombie reaction. Thus, glycosylation of 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside (4) with octa-O-acetyl-β-maltose (3) gave tetrasaccharide 5 with only one free hydroxyl group at the 4-position. The 4′-position of an allyl maltoside was available selectively after removal of a 4′,6′-cyclic acetal and selective benzoylation of the 6′-position. Reduction of this derivative 11 afforded allyl O-(2,3-di-O-acetyl-6-O-benzoyl-4-deoxy-α-D-glucopyranosyl)-(1→4)-2,3,6-tri-O-acetyl-β-D-glucopyranoside (14), which was deallylated, activated as an trichloroacetimidate, and coupled to 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (20). Several compounds were fully characterized by ...

Selectively deoxygenated sulfated tetrasaccharides as probes for the investigation of smooth muscle cell antiproliferative activity

Abstract Selectively deoxygenated analogues of highly (ca. 80 %) sulfated β-maltosyl-(1→4)-α,α-trehalose were investigated to map the importance of the individual sulfates for biological activity. Single deoxygenations led to activity losses up to 30 %; the essential sulfates are located on the outer glucopyranosyl rings of the molecule.

The Synthesis of Four Dideoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose

Abstract Four derivatives of β-maltosyl-(1→4)-trehalose were prepared, each with two deoxy functions in one of the constitutive disaccharide building blocks. 2,3-Di-O-acetyl-4,6-dideoxy-4,6-diiodo-α-D-galactopyranosyl- (1→4) −1,2,3,6-tetra-O-acetyl-D-glucopyranose (3) was employed as a precursor for the 4‴,6‴-dideoxygenated tetrasaccharide 9: coupling of 3 with 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3,6-tri-O-benzylidene-α-D-glucopyranoside (4) furnished the tetrasaccharide 5 which was deiodinated and deprotected to yield the target tetrasaccharide 9. Secondly, the dideoxygenated maltose derivative 3-deoxy-4,6-O-isopropylidene-2-O-pivaloyl-β-D-glucopyranosyl- (1→4) −1,6-anhydro-3-deoxy-2-O-pivaloyl-β-D-glucopyranose (10) was ring-opened to the anomeric acetate 11. A [2+2] block synthesis with 4 in TMS triflate mediated glycosylation gave a tetrasaccharide which was deprotected to the 3″,3‴-dideoxygenated analogue of β-maltosyl-(1→4)-trehalose. For the third tetrasaccharide, 2,3,2″,3′-tetra-O-benzyl-α,α-t...

Pivalates in the selective protection and activation of maltose for the synthesis of sulfated 3-deoxy-maltosyl-(1 → 4)-α,α-trehalose

Abstract Pivaloylation of maltose gave, in satisfactory yield, 1,2,6,2′,3′,4′,6′-hepta- O -pivaloyl-β-maltose which was converted to the 3-deoxygenated analogue in a Barton-McCombie reaction. This compound was used directly in a trimethylsilyl triflate-mediated glycosylation reaction with 2,3,6-tri- O -benzyl-α- d -glucopyranosyl 2,3-di- O -benzyl-4,6- O -benzylidene-α- d -glucopyranoside to give the corresponding maltosyl-(1 → 4)-α,α-trehalose derivative. After deprotection, the monodeoxygenated tetrasaccharide was sulfated; in the reaction product, one compound fully sulfated at the outer pyranose rings predominated.

The Synthesis of the 2′′- and 2′′′-Monodeoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose

Abstract Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at C-2′′ or C-2′′′ have been synthesized in [2+2] block syntheses. O-(2,3,4,6-Tetra-O-benzyl-α-D-glucopyranosyl)-(1→4)-3,6-di-O-benzyl-1,2-di-O-acetyl-β-D-glucopyranose (6), prepared from the respective orthoester, was coupled to the glycosyl acceptor 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside. In the resulting tetrasaccharide 8, the only ester group was removed and replaced by a xanthate which was reduced in a Barton-McCombie reaction to afford the 2′′-deoxygenated tetrasaccharide 12. For the synthesis of a 2′′′-deoxygenated derivative, a maltose building block was assembled from two monosaccharides. The key building block was ethyl 2,3,6-tri-O-benzyl-1-thio-β-D-glucopyranoside (14) which was used i) as a glycosyl acceptor in a phenylselenyl chloride mediated coupling reaction with tri-O-benzyl-glucal and ii) after the first coupling as a glycosyl donor to react with glycosyl acceptor ...