{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T13:28:39Z","timestamp":1780061319771,"version":"3.54.0"},"reference-count":32,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T00:00:00Z","timestamp":1598572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Clarithromycin and congeners are important antibacterial members of the erythromycin A 14-membered macrocyclic lactone family. The macrolide scaffold consists of a multifunctional core that carries both chemically reactive and non-reactive substituents and sites. Two main approaches are used in the preparation of the macrolides. In semisynthesis, the naturally occurring macrocycle serves as a substrate for structural modifications of peripheral substituents. This review is focused on substituents in non-activated positions. In the total synthesis approach, the macrolide antibiotics are constructed by a convergent assembly of building blocks from presynthesized substrates or substrates prepared by biogenetic engineering. The assembled block structures are linear chains that are cyclized by macrolactonization or by metal-promoted cross-coupling reactions to afford the 14-membered macrolactone. Pendant glycoside residues are introduced by stereoselective glycosylation with a donor complex. When available, a short summary of antibacterial MIC data is included in the presentations of the structural modifications discussed.<\/jats:p>","DOI":"10.3390\/molecules25173941","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T10:23:08Z","timestamp":1598610188000},"page":"3941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Scaffold Modifications in Erythromycin Macrolide Antibiotics. A Chemical Minireview"],"prefix":"10.3390","volume":"25","author":[{"given":"Kjell","family":"Undheim","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Oslo, 0315 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1021\/cr030107f","article-title":"Translation and protein synthesis: Macrolides","volume":"105","author":"Katz","year":"2005","journal-title":"Chem. Rev."},{"key":"ref_2","first-page":"35","article-title":"Ribosome-targeting antibiotics and mechanisms of bacterial resistance","volume":"12","author":"Wilson","year":"2014","journal-title":"Nat. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1111\/bph.13936","article-title":"The macrolide antibiotic renaissance","volume":"174","author":"Dinos","year":"2017","journal-title":"Br. J. 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