Total synthesis of landomycins Q and R and related core structures for exploration of the cytotoxicity and antibacterial properties

Abstract

Herein, we report the total synthesis of landomycins Q and R as well as the aglycone core, namely anhydrolandomycinone and a related core analogue.

Direct Synthesis of 2,6‐Dideoxy‐β‐glycosides and β‐Rhamnosides with a Stereodirecting 2‐(Diphenylphosphinoyl)acetyl Group

“…However, these late‐stage conversions of β‐ d ‐mannosides to β‐ d ‐rhamnosides could result in multiple byproducts, [5a,b, 17c] particularly on complex substrates bearing diverse functional groups. Hence, it would be more efficient to directly use d ‐rhamnosyl donors and even the more challenging oligosaccharide donors to construct the aforementioned Citrobacter O‐antigen composed with the [→4)‐α‐ d ‐Man p ‐(1→3)‐β‐ d ‐Rha p (1→4)‐β‐ d ‐Rha p ‐(1→] repeating unit.…”

Landomycins as glutathione-depleting agents and natural fluorescent probes for cellular Michael adduct-dependent quinone metabolism

“…1 ) 5 – 7 . Besides extraction and purification from bacterial cultures, strategies for total chemical synthesis of several landomycins have been developed 8 – 10 . Landomycin A (LA) and landomycin E (LE), containing six and three saccharide residues, respectively, are the most studied compounds of this family 3 , 7 , 11 – 13 .…”

Rapid spectrophotometric detection for optimized production of landomycins and characterization of their therapeutic potential

“…In another study, landomycin R (lanR) – an anhydro-landomycin with a disaccharide glycan – was more inhibitory than landomycin Q, which only differs from lanR by an extra rhodinose on the glycan chain. 38 Similarly, lanR only differs from lanD by the loss of an alcohol group and subsequent formation of a carbon-carbon double bond in the polyketide core, yet we found lanD to be far less active against S. aureus than was previously found for lanR (7 & 14 μM vs. 104 μM, respectively). Together, these findings better elucidate some of the activity-defining moieties of landomycins.…”

“…Alhough landomycins are commonly reported to exert antimicrobial activity, the knowledge of their activity spectra are unknown. [38][39][40] Additionally, the different landomycins, complex and impure mixtures, and/or qualitative metrics used in these studies limits comparison between them. We screened the five major landomycins found in production cultures for their antimicrobial activity against a diverse array of microbes (five Gram-positive, three Gram-negative, and two fungi) using an agar well diffusion assay.…”