C. E. Dreef

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.

Use of 2-methylsulfonylethyl as a phosphorus protecting group in oligonucleotide synthesis via a phosphite triester approach

2-Methylsulfonylethoxy dichlorophosphine has been converted into the mono-N-morpholino derivative and applied for the preparation of 5′-O,N-protected d-nucleoside-3-phosphoramidites. The latter intermediates could be used in the presence of 1-hydroxybenzotriazole for the formation of 3′-5′-phosphotriester linkages. The MSE protecting group can be removed selectively and fast under mild basic conditions.

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 5-phosphonate analogues of myo-inositol 1,4,5-trisphosphate : possible intracellular calcium antagonists

Abstract The racemic 5-phosphonate analogues IV and V of myo -inositol 1,4,5-trisphosphate were readily accessible by bisphosphorylation of the common precursor 6 , removal of the p -methoxybenzyl group, phosphonylation and subsequent hydrogenolysis of the benzyl protecting groups. The methylphosphonate analogue IV acted as a calcium antagonist in permeabilized human platelets, whereas the (difluoromethyl)phosphonate V exhibited only very little antagonistic activity.

Synthesis of alkylphosphon(othio)ate analogues of DNA

Easily accessible bis(diisopropylamino)alkylphosphines (alkyl is methyl, n-butyl or n-octyl) are convenient reagents for the synthesis of DNA fragments having an alkylphosphonate or alkylphosphonothioate linkage at a predetermined site in solution and on solid support.

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.

An expeditious synthesis of biological important myo-inositol phosphorothioates

Abstract The myo -inositol phosphorothioates 6 , 9 , 12 , and 17 were readily accessible from properly protected precursors by phosphitylation with N,N -diisopropyl dibenzyl phosphoramidite ( 1 ), subsequent in situ sulfurization of the intermediate phosphite triesters with phenacetyl disulfide ( 3 ), and removal of all benzyl protecting groups.

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.