Process for the preparation of macrolide antibacterial agents

A process for preparing a compound of formula (I)

• wherein
• R1 is a monosaccharide or polysaccharide;
• A is —CH2—, —C(O)—, —C(O)O—, —C(O)NH—, —S(O)2-, —S(O)2NH—, —C(O)NHS(O)2-;
• B is —(CH2)n— where n is an integer ranging from 0-10, or B is an unsaturated carbon chain of 2-10 carbons, which may contain any alkenyl or alkynyl group;
• C represents 1 or 2 substituents independently selected in each instance from the group consisting of hydrogen, halogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, heteroarylalkyl, aminoaryl, alkylaminoaryl, acyl, acyloxy, sulfonyl, ureyl, and carbamoyl, each of which is optionally substituted;
• V is —C(O)—, —C(═NR11)—, —CH(NR12R13)—, or —N(R14)CH2—;
• where R11 is hydroxy or alkoxy, R12 and R13 are each independently selected from the group consisting of hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, heteroarylalkyl;
• dimethylaminoalkyl, acyl, sulfonyl, ureyl, and carbamoyl;
• R14 is hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, heteroarylalkyl, dimethylaminoalkyl, acyl, sulfonyl, ureyl, or carbamoyl;
• W is hydrogen, F, Cl, Br, I, or OH;
• X is hydrogen;
• and Y is OW;
• where R7 is hydrogen, a monosaccharide, a disaccharide, alkyl, aryl, heteroaryl, acyl, or —C(O)NR8R9, where R8 and R9 are each independently selected from hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, heteroalkyl, aryl, heteroaryl, heteroarylalkyl, alkoxy, dimethylaminoalkyl, acyl, sulfonyl, ureyl, and carbamoyl;
• or X and Y taken together with the attached carbon to form C═O;
• and pharmaceutically acceptable salts, solvates, and hydrates thereof;
• the process comprising the step of (a) reacting a compound of formula (IV)
• wherein R1 is a saccharide that includes a 2′-hydroxyl group, with a sterically hindered acylating agent R1a-L, wherein R1a is a sterically hindered acyl group and L is a leaving or activating group, to form the corresponding 2′-acyl derivative.