Synergistic Anti-Candida Activity of Bengazole A in the Presence of Bengamide A †.

Bengazoles A⁻G from the marine sponge Jaspis sp. exhibit potent in vitro antifungal activity against Candida spp. and other pathogenic fungi. The mechanism of action (MOA) of bengazole A was explored in Candida albicans under both liquid culture and surface culture on Mueller-Hinton agar. Pronounced dose-dependent synergistic antifungal activity was observed with bengazole A in the presence of bengamide A, which is also a natural product from Jaspis sp. The MOA of bengazole A was further explored by monitoring the sterol composition of C. albicans in the presence of sub-lethal concentrations of bengazole A. The GCMS of solvent extracts prepared from liquid cultures of C. albicans in the presence of clotrimazole-a clinically approved azole antifungal drug that suppresses ergosterol biosynthesis by the inhibition of 14α-demethylase-showed reduced cellular ergosterol content and increased concentrations of lanosterol and 24-methylenedihydrolanosterol (a shunt metabolite of ergosterol biosynthesis). No change in relative sterol composition was observed when C. albicans was cultured with bengazole A. These results eliminate an azole-like MOA for the bengazoles, and suggest that another as-yet unidentified mechanism is operative

NanomoLe-scaLe naturaL products discovery

The discovery and structure elucidation of natural products has advanced through significant developments in spectroscopic techniques, particularly nuclear magnetic resonance (NMR). Improvements in microprobe, microcoil and cryoprobe designs have increased NMR sensitivity by 20-fold over instruments that were available just 10 years ago. The era for the exploration of rare natural products at the 'nanomole-scale' has arrived. This review surveys the development of spectroscopic methods and presents case studies of natural product structure elucidation using extremely small samples. The road to the future of natural product discovery is lined with exciting possibilities that will take advantage of developments already reported, as well as those yet to come

Cyclic azole-homologated peptides from Marine sponges

This review discusses the chemistry of cyclic azole-homologated peptides (AHPs) from the marine sponges, Theonella swinhoei, other Theonella species, Calyx spp. and Plakina jamaicensis. The origin, distribution of AHPs and molecular structure elucidations of AHPs are described followed by their biosynthesis, bioactivity, and synthetic efforts towards their total synthesis. Reports of partial and total synthesis of AHPs extend beyond peptide coupling reactions and include creative construction of the non-proteinogenic amino acid components, mainly the homologated heteroaromatic and α-keto-β-amino acids. A useful conclusion is drawn regarding AHPs: despite their rarity, exotic structures and the potent protease inhibitory properties of some members, their synthesis is under-developed and beckons solutions for outstanding problems towards their efficient assembly

Resolution of Atropisomeric Cyclic Catechol Monoether O-Sulfate Esters by a Molluscan Sulfatase.

Atropisomeric cyclic catechol ethers are notoriously difficult to resolve by classical chiral phase high-performance liquid chromatography. Here, we show the first application of sulfatase enzymes for the kinetic resolution of O-sulfato-catechol ethers with enantioselectivities ranging from 30 to 65% ee, as determined by preparation of their Marfey's ether derivatives. Substrate-structure dependence was briefly explored

Six Trikentrin-like Cyclopentanoindoles from Trikentrion flabelliforme. Absolute Structural Assignment by NMR and ECD

Six new cyclopenta[g]indoles were isolated from a West Australian sponge, Trikentrion flabelliforme Hentschel, 1912, and their structures elucidated by integrated spectroscopic analysis. The compounds are analogues of previously described trikentrins, herbindoles, and trikentramides from related Axinellid sponges. The assignment of absolute configuration of the new compounds was carried out largely by comparative analysis of specific rotation, calculated and measured ECD, and exploiting van't Hoff's principle of optical superposition. Five of the new compounds were chemically interconverted to establish their stereochemical relationships, leading to a simple chiroptical mnemonic for assignment of the this family of chiral indoles. The first biosynthetic hypothesis is advanced to explain the origin of the trikentrin-herbinole family and proposes a pyrrole-carboxylic thioester-initiated polyketide synthase mechanism