Moenomycin synthesis

Scheme 4.63 Multiple use of the sulfoxide glycosylation in the synthesis of the moenomycin A pentasaccharide.

S. Riedel, A. Donnerstag, L. Hennig, P. W. Richter, K. Hobert, and D. M. van Heijenoort, Synthesis and transglycosylase-inhibiting properties of a disaccharide analogue of moenomycin A lacking substitution at C-4 of unit F, Tetrahedron, 55 (1999) 1921-1936. 

F Huber, F Nesemann. Moenomycin an inhibitor of cell wall synthesis. Biochem Biophys Res Commun 30 7-13, 1968. 

Moenomycin S. ghanaensis Cell wall synthesis Antibacterial, growth promotant... 

Natural products have played a major role in the field of antibiotics. Most of their impact has resulted directly from the natural product itself or from single-compound analog synthesis. However, the use of natural-product-template-driven library approaches has the potential to identify novel agents with a new spectrum of activity. The identification of novel antibiotics from the natural products moenomycin and anisomycin demonstrates the viability of the natural product template strategy. These examples also highlight some of the strategies and challenges associated with this approach. 

MoUer, U. et al., Moenomycin A — structure-activity relations synthesis of the D-galacturonamide analogue of the smallest antibiotically active degradation prodnct of moenomycin. Tetrahedron, 49, 1653, 1993. 

Ghosh, M., Kakarla, R., and Sofia, M.J., Diastereofacial selection in the 1,2-addition of MeMgX and MeLi to 4-0X0 sugar efficient synthesis of 4-C-methyl-l-S- i-D-gluco- and galactopyranoside building blocks of moenomycin. Tetrahedron Lett., 40, 4511, 1999. 

In Chapter 8, Sofia describes two approaches for the synthesis of novel antibiotics using moenomycin and anisomycin as synthetic templates. 

Bacitracin, a cyclic peptide, has been shown to block mucopeptide synthesis by inhibiting the dephosphorylation of a lipid pyrophosphate intermediate to lipid phosphate. It prevents the lipid carrier from further participating in the reaction cycle of peptidoglycan synthesis causing accumulation of the lipid pyrophosphate23a,b. The antibiotics enduramycin a (g, basic polypeptide), moenomycin b j d prasinomycin (two phosphorus containing antibiotics) are also inhibitors of mucopeptide synthesis. However, the specific reaction inhibited by these three antibiotics is still not well known. 

The synthesis of the biosynthetic chitobiosyl donor (46) by a mixed chemical/enzymic process involved attachment of 3,4,6-tri-0-acetyl-2-deoxy-2-acetamido-tt-D-glucose to dolichol via a pyrophosphate bridge by chemical means as shown in Scheme 9. The monosaccharide pyrophosphate (45) then served, after deprotection, in an enzymic formation of the disaccharide (46). Derivatives (47) of 2-deo -2-acetamido>a-D-glucose 1-phosphate were prepared as simple analogues of moenomycin, a complex pentasaccharide which inhibits bacterial cell wall transglycosidation. ... 

References to the synthesis of a part-structure of papulacandin and of disaccharide analogues of a moenomycin degradation product are given in Chapter 3, and a synthesis of prumycin from D-arabinose is referred to in Chapter 9. 

Homoenolate Reactivity. Since the previous e-EROS report, a number of examples have been described using the cyclopropanone acetals. Thus, the zinc homoenolate, known to undergo a highly regioselective and stereoselective Sn2 allylation reaction (eq 6), is used in the synthesis of moenomycin analogues. The activated titanium homoenolate reacts with aldehydes or ketones to give y-hydroxy esters that serve as precursors to y-lactones. ... 

The IBX oxidation of carbohydrate 290 was employed in the synthesis of moenomycin A disaccharide analogs (Scheme 74 1999T687). 

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