Noteworthy, using the per-O-acylated 1-thionoviose 9-b in the newly established two-step protocol gave access to the single atom exchanged analogue of OP-1118 (18e-C (11), S-OP1118), the main metabolite of Fdx. For the thioglycosides 18a-e, we observed a product distribution favoring the C(15)-isomer (11-24%), followed by the C(13)-isomer (<5-9%) and the C(11)-isomer (≤5%) (Fig. ). The product distribution in all synthesized Fdx derivatives suggests the C(15)-position to be more readily accessible or also that in addition to the suggested SN1 type mechanism a competing SN2'' reaction could be operational. Interestingly, the loss of activity comparing Fdx to S-Fdx is of similar magnitude as of Fdx to OP-1118. This suggests that modification of the ester moiety in 4-position of the noviose constitutes a promising strategy to recover some activity lost upon O-/S-exchange. Thus, we examined the effect of first modifications of the acyl group. The antibacterial activity of the acyl derivatives of S-Fdx was assessed by means of MIC against C. diff. and C. perfringens (Table , Suppl. Tab. 9). MIC determination was performed by the broth microdilution method. Exchanging a single atom from Fdx to S-Fdx resulted in a decreased activity of 0.12-2 µg/mL against C. diff. and 0.06-0.12 µg/mL against C. perfringens. A slightly decreased activity was observed for the acyl derivatives 3b-C(11) and 3c-C (11). In comparison to the nonacylated S-OP1118 (Suppl. Tab. 8), esterification with lipophilic alkyl carbonyl derivatives clearly lead to an increase in antibacterial potency, however not to an extent that makes up for the loss of activity upon O-/S-exchange. Further modification of the ester is necessary to obtain more SAR information. Gratifyingly, all S-Fdx derivatives were found highly active against C. perfringens with MIC values ranging from 0.06 to 0.5 µg/mL. In comparison, the currently used metronidazole (MET) has a MIC range of 1 to 2 µg/mL against the investigated C. perfringens isolates.