Syntheses of Penta-O-benzyl-myo-inositols, O-β-L-Arabinosyl-(1 → 2)-sn-myo-inositol, O-α-D-Galactosyl-(1 → 3)-sn-myo-inositol, and O-α-D-Galactosyl-(1 → 6)-O-α-D-galactosyl-(1 → 3)-sn-myo-inositol

Abstract

(2-O-hexadecyl)PI], were tested as substrates or inhibitors of glycosylphosphatidylinositol (GPI) bio-synthetic pathways using cell-free systems of the proto-zoan parasite Trypanosoma brucei (the causative agent of human African sleeping sickness) and human HeLa cells. Neither these compounds nor their N-acetyl derivatives are substrates or inhibitors of GPI bio-synthetic enzymes in the HeLa cell-free system but are potent inhibitors of GPI biosynthesis in the T.brucei cell-free system. GlcN-(2-O-hexadecyl)PI was shown to inhibit the first α-mannosyltransferase of the trypano-somal GPI pathway. The N-acetylated derivative GlcNAc-(2-O-octyl)PI is a substrate for the trypano-somal GlcNAc-PI deN -acetylase and this compound, like GlcN-(2-O-octyl)PI, is processed predominantly to Man 2 GlcN-(2-O-octyl)PI by the T.brucei cell-free system. Both GlcN-(2-O-octyl)PI and GlcNAc-(2-O-octyl)PI also inhibit inositol acylation of Man 1-3 GlcN-PI and, consequently, the addition of the ethanolamine phosphate bridge in the T.brucei cell-free system. The data establish these substrate analogues as the first generation of in vitro parasite GPI pathway-specific inhibitors.

Structural, Functional and Calorimetric Investigation of MosA, a Dihydrodipicolinate Synthase from Sinorhizobium meliloti L5–30, does not Support Involvement in Rhizopine Biosynthesis

“…Ligand (5). [31] Dichloromethane (1 mL) was added to dissolve the benzyl derivative 4 (0.76 g, 1.7 mmol) at room temperature. The solution was diluted with methanol (15 mL) and Dowex 50W-X8-100 (H + form, 3.5 g) was added.…”

“…Regioselective deprotection of the axial benzyl group to give pentabenzyl 6 is achieved by SnCl 4 in dry dichloromethane. [31] This results in a mixture of deprotected inositols, although the symmetrical pentabenzyl 6 is obtained in 58 % yield. Since unreacted 5 can be recovered from the reaction mixture, subsequent isolation and treatment with SnCl 4 results in greater overall efficiency.…”

Regioselective Protection and Deprotection of Inositol Hydroxyl Groups

“…Traditionally, the hydroxyl groups of 1 were initially protected as ketals of acetone, cyclohexanone, or cyclopentanone; 19a, however, the cyclopentylidene ketals have not been used extensively for synthetic purposes. An attempt 21 to synthesize benzylidene derivatives of myo -inositol led to a mixture of products consisting of myo - and epi -inositol derivatives, but the yields seemed to be irreproducible.…”

“…Angyal et al,19b and later Baker et al,19e synthesized the cyclohexylidene derivative 26 (Scheme ) by the treatment of 1 with cyclohexanone in the presence of an acid catalyst. The monoketal 26 was formed by the in situ hydrolysis of the trans- cyclohexylidene group in the initially formed mixture of bis-cyclohexylidene derivatives.…”

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

“…For our strategy having a moderate selectivity is of great advantage to continue the synthesis with both isolated diastereoisomers myo -8 and scyllo -8 . Next, the ether link was created by the reaction of alcohols myo -8 and scyllo -8 with allyl bromide under classical conditions in the presence of NaH at reflux [ 44 ] to afford myo -9 and scyllo -9 in good yield of 80% and 82%, respectively. The hydroxylated arm was obtained by hydroboration using BH 3 on the unsaturated compounds myo -9 and scyllo -9 followed by an oxidation with H 2 O 2 /NaOH allowing the access to myo -10 and scyllo -10 in 78% and 75% yield, respectively.…”