El-Sayed I. Ibrahim

Synthesis of chitotetraose and chitohexaose based on dimethylmaleoyl protection.

tert-Butyldimethylsilyl 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranoside was readily transformed into the disaccharide glycosyl donor, 3,4,6-tri-O-acetyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-alpha/beta-D-glucopyranosyl trichloroacetimidate, and the disaccharide glycosyl acceptor, tert-butyldimethylsilyl 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranoside. A TMSOTf-catalysed coupling of the acceptor with the donor afforded the respective tetrasaccharide derivative, which can be transformed to chitotetraose. tert-Butyldimethylsilyl 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-4-O-phenoxyacetyl-beta-D-glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranoside was converted into donor 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-4-O-phenoxyacetyl-beta-D-glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl trichloroacetimidate. Its coupling with benzyl 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranoside, followed by dephenoxyacetylation, gave benzyl 3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranosyl-(1 --> 4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-beta-D-glucopyranoside, whose glycosylation furnished, after replacement of the DMM-group by the acetyl moiety and subsequent deprotection, chitohexaose.

The Dimethylmaleoyl Group as Amino Protective Group – Application to the Synthesis of Glucosamine-Containing Oligosaccharides

Glucosamine was readily transformed into N-dimethylmaleoyl (DMM) protected derivative 1 which furnished trichloroacetimidate 4 as glycosyl donor. Reaction with various acceptors (5a–g) in the presence of TMSOTf as the catalyst afforded the corresponding β-glycosides 6a–g generally in high yields. Cleavage of the DMM group was readily accomplished by treatment with aqueous NaOH and then with HCl (pH 5). Starting from 1 also DMM group containing glycosyl acceptors 9 and 14a–c were synthesized. They furnished with trichloroacetimidates 12 and 4 as glycosyl donors β(1-4)- and β(1-3)-linked disaccharides 13 and 15a–c, respectively. From 18 as galactosyl donor and 14a as acceptor β(1-3)-linked disaccharide 19 was obtained in high yield, which is a versatile building block for the important Galβ(1-3)GlcNAc unit. 19 was transformed into trichloroacetimidate 21; glycosylation with 5e as acceptor gave trisaccharide 22 which furnished on partial deprotection Galβ(1-3)GlcNAcβ(1-4)Glc derivative 24. Thus, the wide applicability of DMM as amino protective group in oligosaccharide synthesis is exhibited.

Synthesis of Lacto-N-neohexaose and Lacto-N-neooctaose Using the Dimethylmaleoyl Moiety as an Amino Protective Group

The N-DMM-Protected lactosamine derivative 2 was readily transformed into the corresponding glycosyl donor 4 and into acceptor 5. A TMSOTf-catalyzed glycosidation afforded the derived tetrasaccharide 6 which led to glycosyl donor 9. Reaction of 9 with lactose derivative 10 as acceptor gave the desired hexasaccharide 11. Cleavage of all protective groups and N-acetylation afforded the target molecule 1b (lacto-N-neohexaose). Glycosylation of acceptor 10 with donor 4 furnished tetrasaccharide 16 which, employing standard procedures, gave acceptor 18. Glycosylation of 18 with donor 9 furnished, under standard conditions, octasaccharide 19. Cleavage of all protective groups and N-acetylation afforded the target molecule 1c (lacto-N-neooctaose). Both 1b and 1c were obtained in good overall yields.

Chapter 1 Dimedone: A Versatile Precursor for Annulated Heterocycles

Publisher Summary This chapter explores that dimedone is a versatile precursor for annulated heterocycles. Dimedone(1) is an alicyclic compound having 1,3-dicarbonyl groups flanked by a methylene group and exists in a tautomeric transenolized form where intramolecular hydrogen bonding is not possible. Dimedone is an excellent precursor for partially hydrogenated fused heterocycles where two of the carbon atoms of dimedone are part of the backbone of the formed heterocycles. The chapter illustrates that dimedones structural features and its reactivity to form more functionalized derivatives have led to the construction of a wide range of fused or spiral biheterocycles. Finally, this chapter emphasizes the role of 1 in the synthesis of fused heterocycles, classified according to the size of the ring and the number of heteroatoms in the heterocycle fused to the cyclohexane ring and subdivided according to the heteroatoms and their arrangement in the ring.

Synthesis and anomeric configuration of 2-(erythrofuranosyl)benzimidazole C-nucleoside analogues

Abstract Anomeric 2-(α- and β- d -erythrofuranosyl)benzimidazole C-nucleoside analogues 2 and 3 , were prepared from the corresponding epimeric 2-( d - arabino , and d - ribo -tetritol-1-yl)benzimidazole analogues 1 and 4 , respectively. Similarly, 2-(β- l -erythrofuranosyl)benzimidazole 13 was obtained from the precursor 2-( l - arabino -tetritol-1-yl)benzimidazole 12 . The structure and anomeric configuration of the C-nucleoside analogues 2 , 3 , and 13 were determined by acylation, 1 H and 13 C NMR spectroscopy, and mass spectrometry.

Synthesis of some quinolinyl chalcone analogues and investigation of their anticancer and synergistic anticancer effect with doxorubicin

Two derivatives of 2-(4-acetylanilino)quinolines (IIIa, b) were synthesized as scaffolds for synthesis of open chalcone analogues (Va-f) through Claisen-Schmidt condensation with a set of aromatic aldehydes (IVa-d). Derivatives (Va, b) were further manipulated into cyclic α,β-unsaturated ketones by Michael-addition of acetylacetone and ethylacetoacetate affording derivatives (VI–VII). Deethoxycarboxylation of derivatives (VIIa, b) afforded cyclohexenons (VIIIa, b) allowing formation of a mini library of α,β-unsaturated ketones for screening their anticancer and synergistic anticancer effect with doxorubicin using colon cancer cell line (Caco-2). Two open enones, (Vb) and (Ve), showed significant anticancer activity with IC50 of 5.0 and 2.5 μM respectively. Only one cyclic enone, (VIa) showed synergistic anticancer activity with doxorubicin at 10 μM.