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Chemical Synthesis of Core Structures
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
The synthetic strategy is based on a straightforward, blockwise assembly utilizing the α-(2→8)-linked disaccharide bromide donor 17. Regioselective silylation of the O-allyl α-glycoside 14 at the 8-OH position, followed by O-acetylation and subsequent HF treatment produced 15, which was coupled with the Kdo bromide derivative 6 in MeNO2 in the presence of Hg(CN)2. Thus, a 4:1 mixture of α- and β-(2→8)-linked disaccharides was obtained in 90% yield, from which the α-isomer 16 was isolated by fractional crystallization. Deprotection of 16 with NaOMe and alkaline hydrolysis of the methyl ester groups afforded the disaccharide α-Kdo-(2→8)-α-Kdo-(2→OAll) 18 as a crystalline disodium hemihydrate (23). The crystal structure determination (24) of 18 revealed the presence of an interresidue hydrogen bond between the terminal carboxyl group and 7-OH of the reducing Kdo unit. Furthermore, the disaccharide bromide 17 was made available in four steps from 16 via selective cleavage of the glycosidic allyl group; alternative synthetic pathways for 17 from the readily accessible 13-benzyl ketoside and from the 2-O-acetyl derivative of Kdo have been reported (25,26). Condensation of 17 with the equatorially oriented, reactive 4-OH group of the 7,8-O-carbonyl protected Kdo unit in mono-, di-, and trisaccharide glycosyl acceptor derivatives 19a-cwas effected by variants of the Helferich procedure in fair to modest yields and stereoselectivity to give, after separation of small amounts of β-isomers and subsequent deprotection of 21a-c, the tri-, tetra-, and pentasaccharide derivatives 22 (23), 23 (27), and 24 (28). An improvement in the overall conversion has been accomplished, since the disaccharide glycal ester 20 formed by the competing elimination reaction during the glycosylation steps may be recycled in good overall yields into the disaccharide donor 17 via acetoxyiodination, reduction with Bu3SnH, and treatment with TiBr4 (29). Moreover, a series of Kdo di- and trisaccharide analogs containing carboxyl-reduced Kdo moieties was prepared employing octulopyranosyl fluorides as highly α-selective glycosyl donors in the presence of borontrifluoride etherate (25,26). Immunochemical investigations with neoglycoproteins derived from the oligosaccharides confirmed the trisaccharide and the α-(2→8)-linked disaccharide as the major immunodominant epitopes (22). In addition, a carboxyl-reduced trisaccharide analog containing the carboxyl-reduced moiety at the central Kdo unit also displayed Chlamydia reactivity with monoclonal antibodies (see Chapter 13).
Design of artificial cells: artificial biochemical systems, their thermodynamics and kinetics properties
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Adamu Yunusa Ugya, Lin Pohan, Qifeng Wang, Kamel Meguellati
From the early Sanger work, efforts have been made to study the genetic information of various collections of species over the past 25 years. Studies of the biological roles played by all the genes present in a single cellular system are limited. Another team led by Craig Venter in 2010 was the first to transfect a synthetic genome and study the complete genetic sequence of a self-replicating bacterium, Mycoplasma mycoides, giving a new dimension to scientists working on synthetic self-replicative programs [22]. A lot of effort has been put into the development of enzyme-free DNA replication for the development of a synthetic self-replicative program. The rate of polymerization and fidelity is increased by the replication process with a 3’-NP-DNA (for N3′P5′-linked phosphoramidate DNA) template and a complementary strand of 3’-NP-DNA by the modification of 2-thiothymidine. Thus, it is concluded that 3’-NP-DNA can be used as an efficient genetic material for artificial biological systems [39]. The template-directed polymerization of activated 3’-amino-2’, 3’-dideoxyribonucleotides is used successfully for the synthesis of N3’-P5’-linked phosphoramidate DNA (3’-NP-DNA) [104]. The next work involved the polymerization of TNA oligomers of at least 80 nucleotides in length by terminator DNA polymerase. It is found to be a competent DNA-dependent TNA polymerase with high fidelity [105]. Chen et al. (2009) studied the non-enzymatic, template-directed ligation of 3’-imidazole-activated-2’-amino GNA (glycerol nucleic acid) dinucleotides used for the assembly of GNA oligonucleotides containing N2’-P3’ phosphoramidate linkages (np-GNA). It is also found that npGNA is capable of forming duplexes with itself and with GNA. It is inferred that, based on phosphoramidate linkages, npGNA is a latent self-replication system [106]. Another study based on a cycloaddition reaction between a glycal and an azodicarboxylate followed by direct nucleosidation of the cycloadduct, resulted in the development of a novel method for the synthesis of 2’-amino modified TNA nucleosides (2’-NH2-TNA) was developed. The template of 2’-NH2-TNA was discovered to have poor kinetics and thus cannot be used as a genetic material by biological systems [107].