Synthesis of analogues of the 2-O-alkyl glycerate part of the moenomycins UweEichelberger, a InesNeundorf, a LotharHennig, a MatthiasFindeisen, a SabineGiesa, a DietrichMu Èller b andPeterWelzel a,p a Fakulta Ètfu Èr Organische Chemie und Mineralogie, Universita Èt Leipzig, Johannisallee 29, D-04103 Leipzig, Germany b Institut fu Èr Analytische Chemie, Ruhr-Universita Èt Bochum, D-44780 Bochum, Germany Received16July2001;revised9November2001;accepted20November2001 Abstract ÐThe title compounds have been prepared by hydroxymethylation of chiral enolates q 2002 Elsevier Science Ltd. All rights reserved. 1. Introduction The moenomycin antibiotics (see, for example, moeno- mycinA(1), 1 Scheme 1) are the only compounds known with certainty to inhibit the enzyme of the transglycosyl- ation reaction, 2 oneofthelaststepsinthebiosynthesisof peptidoglycan 3 (main component of the bacterial cell wall). A mechanism for their mode of action has been proposed. 4±6 It is assumed that they are anchored to the cytoplasmic membrane via the lipid part and bind thenhighlyselectivelytotheactivesiteoftheenzymevia the C±E±F trisaccharide. 7 Whereas the structural requirements for antibiotic activity in the carbohydrate part have been investigated in great detail, 7,8 little is knownhowmembraneanchoringassiststheinteractionof the antibiotic with the enzyme. The C 25 lipid may be cyclized in its terminal part 9 as well as saturated without loss of antibiotic activity. 10 However, converting the glyceric acid part into its methyl ester or introducing a single OH group to C-17 or C-18 of the lipid chain abolishes the antibiotic activity completely. Similarly, cleavage of the bond between the glyceric acid unit andtheC 25 lipidleadstoacompounddevoidofantibiotic activity. 11,12 Tetrahedron58(2002)545±559 Pergamon TETRAHEDRON 0040±4020/02/$-seefrontmatter q 2002ElsevierScienceLtd.Allrightsreserved. PII:S0040-4020(01)01167-X Scheme 1. Keywords:antibiotics;alkylation;stereocontrol;oxazolidinones. p Correspondingauthor.Tel.: 149-341-97-36551;fax: 149-341-97-36599;e-mail:welzel@organik.chemie.uni-leipzig.de