In our continuing efforts to elucidate the relationships between the biological activities of iv-acetylmuramoyl-L-alanyl-D-isoglutamine** (MDP) and the structure of the carbohydrate moiety, and to obtain glycopeptide adjuvants that exhibit strong activity and lower toxicity, it was demonstrated that replacement2y3 of the hydroxyl group at C-l of the sugar moiety by a thiol or an acylthio group caused potent antitumor and anti-infection activities, based on the immune reaction, that are not found for MDP itself, as well as strong, immunoadjuvant activities. In view of these facts, we now describe the synthesis of (N-acetyl-6-thiomuramoyl)-L-alanyl-D-isoglutamine derivatives, and their immunoadjuvant activity. 0-Deisopropylidenation of 2-acetamido-I-0-benzoyl-2-deoxy-4,6-O-isopropylidene-3-O-[D-l-(methoxycarbonyl)ethyl]-~-D-glucopyranosez (1) under mildly acidic conditions gave crystalline 2 in quantitative yield. Selective bromination of the primary hydroxyl group on C-6 in 2 with carbon tetrabromide and triphenylphosphine in pyridine afforded the 6-bromo derivative 3 in good yield, and 3 was acetylated with acetic anhydride in pyridine to give the 4-0-acetyl derivative 4; significant signals in the n.m.r. spectrum of 4 were a one-proton triplet at 6 5.16 (J3,4 = Jj,s = 9.0 Hz, H-4), and a one-proton doublet at 6 6.76 (J1,z 3.0 Hz, H-l). Other n.m.r. data, given in the Experimental section, are consistent with structure 4. 0-Debenzoylation of 4 with sodium methoxide in methanol for 2 h at -20" gave 5, and (tetrahydropyran-2-yI)ation of 5 afforded 2-acetamido-4-O-acetyl-6-bromo-2,6-dideoxy-3-O-[~-l-(methoxycarbonyl)ethyl]-l-O-(tetrahydropyran-2yl)-cu-D-glucopyranose (6) in good yield. The structure of compound 6 was based on n.m.r. spectroscopy; the spectrum showed the 0-acetyl group at 6 2.13, the H-4 -__ *Studies on Immunoadjuvant Active Compounds, Part 27. For Part 26, see ref. 1.