Recent Advances in the Chemistry and Biology of Naturally Occurring Antibiotics

Abstract

Ever since the world-shaping discovery of penicillin, nature's molecular diversity has been extensively screened for new medications and lead compounds in drug discovery. The search for anti-infective agents intended to combat infectious diseases has been of particular interest and has enjoyed a high degree of success. Indeed, the history of antibiotics is marked with impressive discoveries and drug development stories, the overwhelming majority of which have their origins in nature. Chemistry, and in particular chemical synthesis, has played a major role in bringing naturally occurring antibiotics and their derivatives to the clinic, and no doubt these disciplines will continue to be key enabling technologies for future developments in the field. In this review article, we highlight a number of recent discoveries and advances in the chemistry, biology, and medicine of naturally occurring antibiotics, with particular emphasis on the total synthesis, analog design, and biological evaluation of molecules with novel mechanisms of action.

Thoughts and facts about antibiotics: Where we are now and where we are heading

“…There are currently two main tasks to solve. To stop the decline of microbial metabolite research and increase the effectiveness of the discoveries, we must complete the following: [12][13][14][15][16][17] 1. Look for new natural resources.…”

“…Glycopeptides and orthosomycins are mainly produced by non-Streptomyces actinobacteria. Small-membered ring lactones (10)(11)(12)(13)(14), benzoquinone derivatives, gliotoxin-like diketopiperazines, peptaibols, grisans, scirpenes, cytocalasins, several distinct types of cyclopeptides (cyclosporins), alpha pyrones, numerous types of terpene types (generally polyketide synthase-derived compounds) are mainly fungal products. Lantibiotics and numerous types of lipocyclopeptides are almost exclusively unicellular bacterial products; however, these microbes never produced macrolides.…”

Paradigm Shifts in Fungal Secondary Metabolite Research: Unusual Fatty Acids Incorporated into Fungal Peptides

“…Avian myeloblastosis virus reversed transcriptase, hepatitis B virus, and prolyl endopeptidase. Ramoplanin exhibits broad-spectrum and potent in vitro and in vivo activity against Gram-positive bacteria (Nicolaou et al, 2009;Pallanza et al, 1984;Cavalleri et al, 1984). Ramoplanin was active against a wide variety of Gram-positive bacteria including enterococci, staphylococci, bacilli, streptococci, Listeria monocytogenes, and Gram-positive anaerobes such as Clostridium difficile.…”

Recent Advances in Iridium-Catalyzed Asymmetric Hydrogenation: New Catalysts, Substrates and Applications in Total Synthesis

“…Bisboronic esters (31-34) also gave access to alkenyl-monoboronic esters, given the higher reactivity of the terminal boron group allowing chemoselective SuzukiMiyaura couplings. Therefore, several alkenyl boronates were prepared (35)(36)(37)(38)(39)(40)(41)(42) in which the terminal boron was replaced by various residues. Subjecting substrates 35-40 to the iridium-catalyzed hydrogenation excellent selectivities ranging from 95% to 99% ee were achieved.…”

“…[35] After Nicolaou reported the first total synthesis of racemic Platensimycin in 2006, [36] several research groups have been involved in an asymmetric approach to it. [37] Among them the Mulzer group has recently reported an elegant approach, [38] which involves two hydrogenation reactions as key synthetic transformations.…”