Synthesis and Antibacterial Activity of Acylides (3-O-Acyl-erythromycin Derivatives):  A Novel Class of Macrolide Antibiotics

Abstract

Introduction of an acyl group to the 3-O-position of erythromycin A derivatives instead of L-cladinose led to a novel class of macrolide antibiotics that we named "acylides". The 3-O-nitrophenylacetyl derivative TEA0777 showed significantly potent activity against not only erythromycin-susceptible Gram-positive pathogens but also inducibly macrolides-lincosamides-streptogramin B (MLS(B))-resistant Staphylococcus aureus and efflux-resistant Streptococcus pneumoniae. These results indicated that acylides have potential as next-generation macrolide antibiotics.

Antibacterial Activity of Novel Sulfonylureas, Ureas and Thioureas of 15-Membered Azalides

“…The discovery of highly potent representatives of the third-generation of macrolides, like ketolides (Agouridas 1998), acylides (Tanikawa et al 2001;Tanikawa et al 2003), anhydrolides (Elliott et al 1998), etc., was a step forward to tackle the efflux problems Pestka & LeMahieu 1974a& 1974bPestka et al 1976;Allen. 1977;Van Bambeke et al 2008)' to (Tanikawa et al, 2001;Tanikawa et al, 2003), anhydrolides (Elliott et al, 1998), etc., was a step forward to tackle the efflux problems Pestka & LeMahieu 1974a& 1974bPestka et al, 1976;Allen.…”

“…1977;Van Bambeke et al 2008)' to (Tanikawa et al, 2001;Tanikawa et al, 2003), anhydrolides (Elliott et al, 1998), etc., was a step forward to tackle the efflux problems Pestka & LeMahieu 1974a& 1974bPestka et al, 1976;Allen. 1977;Van Bambeke et al, 2008).…”

Synthesis and antibacterial activity of 2, 3-dehydro-3-O-(3-aryl-E-prop-2-enyl)-10, 11-anhydroclarithromycin derivatives

“…In addition to ketolides, other macrolides with various substituents at C-3 instead of cladinose have also been designed and investigated over the past decade, such as acylide, 6 3, 6-bicyclolide (Figure 2), 7 2, 3-anhydrolide, 8 2, 3-enol ether, 9 3-deoxy, 10 3-O-phenyl ether, 11 3, 6-ketal 12 and 3, 6-ether. 13 In our search for novel erythromycin derivatives, we previously reported some alkylides (Figure 2) with improved activity against erythromycin-resistant pathogens.…”

“…14 We speculated alkylides, characterized by 3-O-ether bond, might have a profile of higher acid stability and enzyme resistance compared with acylides. 6 More importantly, an allyl group could easily be transformed into other functional groups. 15 For this reason, we synthesized the alkylides to explore their structureactivity relationship.…”

Design, synthesis and antibacterial activity of a novel alkylide: 3-O-(3-aryl-propenyl)clarithromycin derivatives

“…As a result, modification at 3-OH led to the emergence of ketolide, [3][4][5][6] acylide, 7 bicyclolide, 8 anhydrolide, 9 2,3-enol-ether, 10 3-deoxy, 11 3-ether, 12 3,6-ketal 13 and 3,6-ether. 14 Second, an aryl side chain tethered to the erythronolide core is believed to be very important for the improvement of activities against erythromycin-resistant bacteria, due to the interaction with a secondary ribosomal binding site.…”