查看更多>>摘要：Covering: 2011 to 2021Structural division of natural naphthalenoid ansamycins, regarding the type of the core and length of the ansa chain, and their biosynthetic pathways in microorganisms are discussed. The great biosynthetic plasticity of natural naphthalenoid ansamycins is reflected in their structural variety due to the alterations within ansa bridge or naphthalenoid core portions. A comparison between the biological potency of natural and semisynthetic naphthalenoid ansamycins was performed and discussed in relation to the molecular targets in cells. The antibacterial potency of naphthalenoid ansamycins seems to be dependent on the ansa chain length and conformational flexibility – the higher flexibility of the ansa chain the better biological outcome is noted.
查看更多>>摘要：Covering: 2011 to 2021The structural division of ansamycins, including those of atypical cores and different lengths of the ansa chains, is presented. Recently discovered benzenoid and atypical ansamycin scaffolds are presented in relation to their natural source and biosynthetic routes realized in bacteria as well as their muta and semisynthetic modifications influencing biological properties. To better understand the structure–activity relationships among benzenoid ansamycins structural aspects together with mechanisms of action regarding different targets in cells, are discussed. The most promising directions for structural optimizations of benzenoid ansamycins, characterized by predominant anticancer properties, were discussed in view of their potential medical and pharmaceutical applications. The bibliography of the review covers mainly years from 2011 to 2021.
Anna K.,KromeTim,BeckerStefan,KehrausAndrea,Schiefer...
16页
查看更多>>摘要：Covering: August 1984 up to January 2022Worldwide, increasing morbidity and mortality due to antibiotic-resistant microbial infections has been observed. Therefore, better prevention and control of infectious diseases, as well as appropriate use of approved antibacterial drugs are crucial. There is also an urgent need for the continuous development and supply of novel antibiotics. Thus, identifying new antibiotics and their further development is once again a priority of natural product research. The antibiotic corallopyronin A was discovered in the 1980s in the culture broth of the Myxobacterium Corallococcus coralloides and serves, in the context of this review, as a show case for the development of a naturally occurring antibiotic compound. The review demonstrates how a hard to obtain, barely water soluble and unstable compound such as corallopyronin A can be developed making use of sophisticated production and formulation approaches. Corallopyronin A is a bacterial DNA-dependent RNA polymerase inhibitor with a new target site and one of the few representatives of this class currently in preclinical development. Efficacy against Gram-positive and Gram-negative pathogens, e.g., Chlamydia trachomatis, Orientia tsutsugamushi, Staphylococcus aureus, and Wolbachia has been demonstrated. Due to its highly effective in vivo depletion of Wolbachia, which are essential endobacteria of most filarial nematode species, and its robust macrofilaricidal efficacy, corallopyronin A was selected as a preclinical candidate for the treatment of human filarial infections. This review highlights the discovery and production optimization approaches for corallopyronin A, as well as, recent preclinical efficacy results demonstrating a robust macrofilaricidal effect of the anti-Wolbachia candidate, and the solid formulation strategy which enhances the stability as well as the bioavailability of corallopyronin A.
查看更多>>摘要：Covering: up to 2022Pyrroloindoline is a privileged tricyclic indoline motif widely present in many biologically active and medicinally valuable natural products. Thus, understanding the biosynthesis of this molecule is critical for developing convenient synthetic routes, which is highly challenging for its chemical synthesis due to the presence of rich chiral centers in this molecule, especially the fully substituted chiral carbon center at the C3-position of its rigid tricyclic structure. In recent years, progress has been made in elucidating the biosynthetic pathways and enzymatic mechanisms of pyrroloindoline-containing natural products (PiNPs). This article reviews the main advances in the past few decades based on the different substitutions on the C3 position of PiNPs, especially the various key enzymatic mechanisms involved in the biosynthesis of different types of PiNPs.
查看更多>>摘要：Covering: June 2009 to 2021Natural products containing a phloroglucinol motif include simple and oligomeric phloroglucinols, polycyclic polyprenylated acylphloroglucinols, phloroglucinol–terpenes, xanthones, flavonoids, and coumarins. These compounds represent a major class of secondary metabolites which exhibit a wide range of biological activities such as antimicrobial, anti-inflammatory, antioxidant and hypoglycaemic properties. A number of these compounds have been authorized for therapeutic use or are currently being studied in clinical trials. Their structural diversity and utility in both traditional and conventional medicine have made them popular synthetic targets over the years. In this review, we compile and summarise the recent synthetic approaches to the natural products bearing a phloroglucinol motif. Focus has been given on ingenious strategies to functionalize the phloroglucinol moiety at multiple positions. The isolation and bioactivities of the compounds are also provided.
查看更多>>摘要：Covering: July 2010 to August 2021This article summarizes more than 200 cases of misassigned marine natural products reported between July 2010 and August 2021, sorting out errors according to the structural elements. Based on a comparative analysis of the original and the revised structures, major pitfalls still plaguing the structural elucidation of small molecules were identified, emphasizing the role of total synthesis, crystallography, as well as chemical- and biosynthetic logic to complement spectroscopic data. Distinct “trends” in natural product misassignment are evident between compounds of marine and plant origin, with an overall much lower incidence of “impossible” structures within misassigned marine natural products.
查看更多>>摘要：Covering: findings from early 1980s until early 2022Microbial-derived cues of marine biofilms induce settlement and metamorphosis of marine organisms, a process responsible for the emergence of diverse flora and fauna in marine habitats. Although this phenomenon is known for more than 80 years, the research field has only recently gained much momentum. Here, we summarize the currently existing biochemical and microbial knowledge about microbial signalling molecules, con-specific signals, and synthetic compounds that induce or prevent recruitment, settlement, and metamorphosis in invertebrate larvae. We discuss the possible modes of action and conclude with perspectives for future research directions in the field of marine chemical ecology.
查看更多>>摘要：Covering: up to 2022Podophyllotoxin (PTOX, 1), a kind of aryltetralin-type lignan, was first discovered in the plant Podophyllum peltatum and its structure was clarified by W. Borsche and J. Niemann in 1932. Due to its potent anti-cancer and anti-viral activities, it is considered one of the molecules most likely to be developed into modern drugs. With the increasing market demand and insufficient storage of natural resources, it is crucial to expand the sources of PTOXs. The original extraction method from plants has gradually failed to meet the requirements, and the biosynthesis and total synthesis have become the forward-looking alternatives. As key enzymes in the biosynthetic pathway of PTOXs and their catalytic mechanisms being constantly revealed, it is possible to realize the heterogeneous biosynthesis of PTOXs in the future. Chemical and chemoenzymatic synthesis also provide schemes for strictly controlling the asymmetric configuration of the tetracyclic core. Currently, the pharmacological activities of some PTOX derivatives have been extensively studied, laying the foundation for clinical candidate drugs. This review focuses primarily on the latest research progress in the biosynthesis, total synthesis, and pharmacological activities of PTOX and its derivatives, providing a more comprehensive understanding of these widely used compounds and supporting the future search for clinical applications.
NSTL
Royal Soc Chemistry