C. J. J. Elie

Synthesis of 1-O-(1,2-di-O-palmitoyl-sn-glycero-3-phospho)-d-myo-inositol 4,5-bisphosphate: an analogue of naturally occurring (ptd)Ins(4,5)P2

Abstract Optically active 2,3,6-tri-O-benzyl-4,5-di-O-(trans-prop-1-enyl)-D-myo-inositol and 1,2-di-O-palmitoyl-sn-glycerol were coupled using mono- and bifunctional phosphitylating reagents to yield, after final removal of all benzyl-protecting groups the chiral title compound.

Synthesis of 6-0-(α-D-mannopyranosyl)-D-myo-inositol: a fragment from mycobacteria phospholipids

Abstract Condensation of 2-O-acetyl-3,4,6-tri-O-benzyl-α-D-mannopyranosyl fluoride (12) or ethyl 2-O- benzoyl-3,4,6-tri-0-benzyl-1-thio-α-D-mannopyranoside (13) with racemic 1,2-0-cyclohexylidene-3,4,5 tri-O-benzyl- myo-inositol (11) gave, after deacylation and column chromatography, the enantiomorphs 16a and 16b. Benzylation, acid hydrolysis of the 1,2-O-cyclohexylidene group and regioselective allylation of 16b led to 4b, which was deblocked by deallylation and hydrogenolysis to give 6-O-(α-O-D-mannopyranosyl)-D-myo-inositol (5b). Any attempt to glycosylate the hydroxyl at the axial C-2 position of the myo-inositol moiety in 4b with the mannopyranosyl fluoride 12 or the ethyl thiomannopyranoside 13 failed.

Synthesis of 1-O-(1,2-Di-O-palmitoyl-SN-glycero-3-phosphoryl)-2-O-α-D-mannopyranosyl-D-MYO-inositol: a fragment of mycobacterial phospholipids

Abstract Optically active and partially benzylated 1-O-(2-O-α-D-mannopyranosyl)-D-myo-inositol was coupled, via a trivalent phosphorus method, with 1,2-di-O-palmitoyl-sn-glycerol. Oxidation of the intermediate phosphite-triester, and subsequent removal of the P(V)- and O-benzyl protecting groups, afforded the chiral title compound.

Iodonium Ion-Mediated Mannosylations of Myo-Inositol : Synthesis of a Mycobacteria Phospholipid Fragment

Abstract Iodonium ion-mediated glycosylation of 1-O-allyl-3,4,5-tri-O-benzyl-6-O-para-methoxybenzyl-D/L-myo-inositol by ethyl 2-O-benzoyl-3,4,6-tri-O-benzyl-l-thio-α-D-mannopyranoside gave, after removal of the para-methoxybenzyl group and column chromatography, an α/β-mixture of the individual diastereoisomeric disaccharides. Subsequent stereospecific glycosylation of the α(1-2) linked mannopyranosyl-D-myo-inositol enantiomorph by the same ethyl 1-thiomannopyranoside donor afforded, after debenzoylarion, benzylation and subsequent deallylation the partially benzylated 2,6-dimannopyranosyl-D-myo-inositol derivative, the HO-1 position of which was phosphorylated, via the H-phosphonate method, with 1,2-dipalmitoyl-sn-glycerol. Oxidation of the intermediate phosphonate diester, and subsequent hydrogenolysis of the O-benzyl groups, furnished the target compound 1-O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)-2,6-di-O-α-D-mannopyranosyl-D-myo-inositol.

Synthesis of racemic 3-methylphosphonate analogues of myo-inositol 3,4-bis- and 1,3,4-trisphosphate

Abstract The partially benzyl protected myo -inositol derivatives 11a and 11b , the C-4 and C-1,4 hydroxyl function(s) of which are protected with temporary trans -prop-1-enyl protecting group(s), were readily converted into the respective title compounds 18a and 18b by sequential methylphosphonylation, mild cleavage of the trans -prop-1-enyl group(s), phosphorylation and removal of all permanent benzyl protecting groups.

Benzyl-2,4-Diacetamido-2, 4,6-Tri-Deoxy-α(β) -D-Galactopyranoside

Abstract Benzyl-2,4-diacetamido-2,4,6-trideoxy-α(β)-D-galactopyranoside 6c was synthesized from l,6-anhydro-2,3-O-(4-methoxybenzylidene)-β-D-mannopyranose la. The azide group at C-4, which is a precursor for the acetamido function, was introduced by substitution of the 4-O-triflate group with lithium azide. After regioselective oxidative acetal ring opening the other C-2 azide function was obtained by the same substitution procedure. Acetolysis of the 1,6-anhydro bridge and α(β)-coupling with benzyl alcohol gave the 2,4-diazido derivative 4b. After base treatment the azide groups were reduced and subsequently acetylated. Selective protection of the primary hydroxyl by the phenyl thionocar-bonyl group followed by reduction afforded the title compound.

Use of (phenyldimethylsilyl)methoxymethyl and (phenyldimethylsilyl)methyl ethers as protecting groups for sugar hydroxyls

Abstract The reagent (phenyldimethylsilyl)methoxymethyl chioride (SMOM-Cl) proved to be very convenient for the formation of the corresponding SMOM ethers of primary and secondary hydroxyls of sugars. Further, (phenyldimethylsilyl)methanol (SMOH), the precursor of SMOM-Cl, could be used for the protection of the anomeric centre with the SM group. Both protecting groups can be removed smoothly by oxidation with KBr/AcOOH, and are compatible with protecting group manipulations in sugar chemistry.

SYNTHESIS OF PHOSPHONATE ANALOGUES OF MYO-INOSITOL PHOSPHOLIPIDS

Abstract The phosphonate analogues I and II of Ptdlns and Ptdlns[4]P, respectively, were prepared by alkylation of the α-lithio anion of a properly protected D - myo -inositol methylphosphonate diester with 1,2-isopropylidene- sn -glycerol 3-trifluoromethanesulfonate, followed by protective group manipulation and deprotection.