El-Sayed H. El-Ashry

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.

INHIBITION OF SOME HEPATIC GLYCOSIDASES BY THE DISECO NUCLEOSIDE, 4-AMINO-3-(D-GLUCOPENTITOL-1-YL)- 5-MERCAPTO-1,2,4-TRIAZOLE AND ITS 3-METHYL ANALOG

ABSTRACT The in vivo and in vitro effects of 4-amino-3-(D-glucopentitol-l-yl)-5-mercapto-1,2,4-triazole and its 3-methyl analogue on α- and β-glucosidases, β-glucuronidase as well as α-amylase have been investigated. α-Glucosidase is the enzyme that is markedly affected in vivo and in vitro in a dose-dependent manner. The compounds showed a reversible inhibition of a competitive type for α-glucosidase. Moreover, they exert a relatively potent inhibition on α-glucosidase with a Ki magnitude of 3.6×10−4, 9.5×10− 5 M.

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.

Inhibition of some hepatic lysosomal glycosidases by ethanolamines and phenyl 6-deoxy-6-(morpholin-4-yl)-β-d-glucopyranoside

The hepatic lysosomal glycosidases alpha-glucosidase and beta-glucuronidase were inhibited in vitro and in vivo by mono- and diethanolamines. The in vivo inhibition is dose dependent and occurs at a value less than LD50. Phenyl 6-deoxy-6-(morpholin-4-yl)-beta-D-glucopyranoside inhibited alpha-glucosidase both in vitro and in vivo. The treatment of the enzymes in vitro by ethanolamine exhibited a reversible inhibition of the mixed and competitive types for alpha-glucosidase and beta-glucuronidase, respectively. Diethanolamine showed a reversible inhibition of the competitive type for both enzymes. It is a potent inhibitor for beta-glucuronidase, in vitro, whose inhibition constant (Ki) is 5 x 10(-5) M. Phenyl 6-deoxy-6-(morpholin-4-yl)-beta-D-glucopyranoside is a potent inhibitor only for hepatic alpha-glucosidase with a Ki value of 1.6 x 10(-5) M. The pattern of the pH dependence of enzymic activity was not affected by ethanolamine inhibition. The magnitude of the inhibition of enzymes is dependent on the structure of the inhibitor.

Fused Heterocyclo-Quinolines Containing One Nitrogen Atom at Ring Junction: Part 1. Four and Five Membered Heterocyclo-Quinolines

Publisher Summary This chapter discusses the chemistry and biological aspects of four- and five-membered heterocyclo-quinolines containing one nitrogen atom at the ring junction. They were subdivided according to the number of heteroatoms in the heterocyclic rings. Heterocycloquinolines can be identified into three categories; (x, y-a), (x, y, z-ij) and (x, y-j) based on the possibility of fusion on the quinoline ring. The x, y, and z denote the side of the heterocyclic ring, which is fused to the quinoline ring, whereas a, i, and j denote the quinoline bonds to which the heterocycle is fused. Increasing the variation and/or number of heteroatoms in the heterocyclic ring system may increase the number of possibilities of the isomeric structures. The tricyclic systems included in this chapter is classified according to the size of the heterocyclic ring and subdivided according to the number of heteroatoms in those rings. Many of these heterocycles are of potential therapeutic value, which leads to intensive research in the topic.

Recycling of Pharmaceutical Waste Gelatin for Controlled Release Applications II: A Tri-fluralin Based System

Abstract During the latter half of last century, the production and consumption of synthetic plastics and fibers has vastly grown. The plastics wastes have continuously increased over recent decades. Concerns over this have now resulted in mandatory recycling laws and demands for degradable polymers. Management of plastic wastes cannot be treated as an individual problem; it must be considered as an integral part of the global waste management system. The development of recycling processes leading to higher quality recycled products would help the recycling economy. In this study, recycling of pharmaceutical gelatin scraps will be conducted by incorporating them in biodegradable mulching films. The formulation and preparation of these films is described and the effect of different additives on the rate of release of the bioactive agent (trifluralin) is reported. The results showed that the produced films have controlled release properties and the presence of cross-linked agent decreased the release rate of trifluralin.

SYNTHESIS OF 15H-ISOQUINO[2′,3′:3,4]IMIDAZO[2,1-B]QUINAZOLINE-7,13,15-TRIONES AND 14H-ISOQUINO[2′,3′:3,4]IMIDAZO[2,1-B]BENZO[G]QUINAZOLINE-8,14,16-TRIONE AS NEW POLYCYCLIC FUSED-RING SYSTEMS

3-Thioxo-2H-imidazo[1,5-b]isoquinoline-1,5-dione (3) and 2-sub-stituted 3-thioxo-2H-imidazo[1,5-b]isoquinoline-1,5-diones (4a–l) were prepared from the reaction of 2-thiohydantoin (2) and 3-substituted 2-thiohydantoin (5a–l) with 2-formyl benzoic acid (1). Alkylation of 3 under an anhydrous basic conditions afforded 4a–i. The alkylation of 3 in aqueous basic solution afforded 3-(alkylmercapto)imidazo[1,5-b]isoquinoline-1,5-diones (7a,b). Reactions of the aromatic amino acids 9a,b and 12 with 7a afforded 2-(2H-1,5 dioxoimidazo[1,5-b]isoquinazolin-3-ylideneamino)benzoic acids (10a, b) and 3-(2H-1,5-dioxoimidazo[1,5-b]isoquinazolin-3-ylideneamino)2-naphthalenecarboxylic acid (13), which were then cyclyzed by heating in acetic anhydride to afford 15H-isoquino[2′,3′ :3,4] imidazo[2,1-b]quinazoline-7,13,15-triones (11a,b) and 14H-isoquino[2′,3′:3,4]imidazo[2,1-b]benzo[g]quinazoline-8,14,16-trione (14). Some of the new compounds were tested for their antitumor activities.

Copper(II), nickel(II) and cobalt(II) complexes of 5,5-dimethylcyclohexane-1,2,3-trione-2-arylhydrazones

SummaryCopper(II), nickel(II) and cobalt(II) perchlorate complexes of 5,5-dimethylcyclohexane-1,2,3-trione-2-(p-nitrophenyl-hydrazone) (HL1), 5,5-dimethyl-cyclohexane-1,2,3-trione-2-(p-chlorophenylhydrazone) (HL2), 5,5-dimethylcyclohexane-1,2,3-trione-2-(o-chlorophenylhydrazone) (HL4), 5,5-dimethylcyclohexane-1,2,3-trione-2-(o-methylphenyl-hydrazone) (HL5) and 5,5-dimethylcyclohexane-1,2,3-trione-2-(m-methylphenylhydrazone) (HL6) have been prepared, and characterized using analytical, spectral and magnetic measurements. The data reveal that the reaction of Cu(ClO4)2 (1 mol) in EtOH, with all ligands, produces complexes of the type CuL(ClO4)(H2O).nH2O. Nickel(II) and cobalt(II) perchlorates react only with HL1 and HL2 to produce the complexes ML(ClO4)(H2O)3 (where M = NiII, L = L− and L2, M = CoII, L = L1) and Co(HL2)2-(ClO4)2.2H2O. The spectral data show that the ligands behave as monobasic bidentate in their azo forms, except HL2 which reacts with cobalt(II) as a neutral bidentate ligand in its hydrazone form.