O side chains

The Cornforth rearrangement involves the thermal interconversion of 4-carbonyl substituted oxazoles, with exchange between the C-C-O side-chain and the C-C-O fragment of the oxazole ring. These reactions generally involve compounds where a heteroatom (-OR, -SR, -Cl) is attached to the 5-position (R2) of the starting oxazole. 

Baumgartner, J.D., Heumann, D., Gerain, J., Weinbreck, P., Grau, G.E., Glauser, M.P. Association between protective efficacy of anti-lipopolysaccharide (LPS) antibodies and suppression of LPS-induced Tumor necrosis factor a and interleukin 6. Comparison of O side chain-specific antibodies with core LPS antibodies. J Exp Med 171 (1990) 889-896. 

Kim, K.S., Kang, J.H., Cross, A.S., Kaufman, B., Zollinger, W., Sadoff, J. Functional activities of monoclonal antibodies to the O side chain of Escherichia coli lipopolysaccharides in vitro and in vivo. J Infect Dis 157 (1988) 47-53. 

SCHEME 14. Asymmetric synthesis of chiral o> side-chain units. 

Scheme 1. Lipid Cycle in the Biosynthesis of S. typhimurium O Side-chains. (P-ACL, antigen-carrier-lipid phosphate. For other abbreviations, see Fig. 1., p. 411.)...

When D-mannosyl-L-rhamnosyl-D-galactosyl-PP-ACL is produced, the trisaccharide units rapidly polymerize to form O side-chain polysaccharide. If cell envelopes from strains unable to synthesize the core are utilized, the polysaccharide is not transferred to the core, and presumably stays attached to P-ACL. This conclusion was based on the observation that the polysaccharide could be extracted only after mild, acid hydrolysis and that a phosphate group was present at the reducing end of the polysaccharide thus obtained. In mutants defective in core synthesis, O side-chains were, indeed, found to accumulate, presumably in a form still linked to P-ACL. ... 

That the repeating units are normally polymerized while still attached to P-ACL, and then transferred to the core, was demonstrated in two ways. (1) Pulse-chase experiments that used a phosphoman-noisomerase mutant of S. typhimurium, where D-mannose- C is incorporated only into O side-chains, indicated a precursor-product type of relationship between free O side-chains (presumably linked to P-ACL before extraction) and LPS-linked, O side-chains. (2) O Side-chains were shown to be elongated at the reducing end, rather than at the nonreducing end. This mechanism, which is later discussed in detail, tends to rule out the possibility that the O side-chain grows by the sequential addition of repeating units on the core LPS. 

When an O side-chain is elongated, a monomeric repeating-unit has to interact with an oligomer of repeating units. Both are linked to carrier molecules, most probably to P-ACL. Here, two possible mechanisms, shown in Fig. 2, may be distinguished. In one mechanism, the monomeric repeating-unit is added to the nonreducing... 

Fig. 2.—Two Theoretically Possible Methods of Chain Elongation in O Side-chain Synthesis, Considered by Bray and Robbins," (In method A, a repeating unit monomer is added to the nonreducing end of the growing O side-chain, which is linked to PP-ACL. In method B, a polymer of the repeating units is transferred onto the nonreducing, terminal sugar of a repeating unit monomer, linked to PP-ACL.)...

Abequose residues in S. typhimurium occur as branches of O side-chain, and are not found in its main chain (see Fig. 1). Indeed, the enzymic polymerization readily occurs in the absence of CDP-abequose, hence, it was thought possible that abequose residues are added after the synthesis of the main chain of O side-chain polysaccharide is completed. However, this hypothesis appears unlikely in view of the following results. (I) Under certain experimental conditions, the incorporation of D-mannose, L-rhamnose, and D-galactose is strongly stimulated by the simultaneous presence of CDP-abe-quose. (2) By skilful manipulation of the conditions of reaction. 

According to Scheme 1, the last reaction in the synthesis of LPS is the joining of completed O side-chain to the core. This unusual reaction, involving the joining of two macromolecules, was found to occur in a cell-free system. O Side-chains linked to P-ACL were generated in vitro in a cell-envelope preparation from a core-deficient mutant, and this particulate preparation was incubated with an exogenous, core LPS this resulted in eflScient transfer of the O side-chain to the core, a transfer catalyzed by an enzyme or enzymes present in the cell-envelope fraction. Unfortunately, a satisfactory method is not yet known for the extraction of O side-chain polysaccharide linked to PP-ACL, and further resolution of this system has not yet been achieved. 

This lipid carrier is, therefore, identical with, or at least very similar to, the C55 lipid involved in the synthesis of D-mannan in Micrococcus lysodeikticus the latter lipid, also, has two internal, trans, double bonds. The former lipid behaves very similarly to the carrier lipid involved in O side-chain synthesis in Gram-negative bacteria, and can substitute for the latter lipid in the O antigen system. This result is not, however, a rigorous proof of identity, as the M. lysodeikticus system is known to be able to use ficaprenol phosphate as efficiently as undecaprenol phosphate. ... 

The second stage occurs in the cytoplasmic membrane and is concerned with transporting the precursors from the cytoplasm to the wall. The key molecule responsible for the translocation is the lipid carrier, undecaprenyl phosphate (Figure 1.11). This highly lipophilic molecule is a C55-iso-prenoid alcohol phosphate. It is involved in the synthesis of several other bacterial wall components, for example the O side chains of lipopoly-... 

Bacterial O-side chains have a basic structural similarity, consisting of... 

Unlike salmonellae, which appear only to possess neutral polysaccharide O-side chains, E, coli has been shown to have both neutral and acidic 0-antigens. The specific neutral polysaccharide of E. coli may be composed of up to six different sugars, often containing unusual amino sugars and rhamnose (Figure 3.18). Only two homopolysaccharide... 

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