Lavanducyanin

Total syntheses of pyocyanin, lavanducyanin, and marinocyanins A and B have been accomplished. The N-substituted phenazin-1-one skeleton, a common framework of these natural products, was constructed through the oxidative condensation of pyrogallol with N-substituted benzene-1,2-diamine under an oxygen atmosphere in a single step. Regioselective bromination with N-bromosuccinimide at the C-2 position of N-alkylated phenazin-1-ones afforded brominated natural products.

Lavanducyanin is a bioactive phenazine-containing secondary metabolite, and naphthomevalin is an antibacterial polyketide secondary metabolite. Herein, new analogues of lavanducyanin (2) and of naphthomevalin (4), together with lavanducyanin (1) and naphthomevalin (3), were identified from Streptomyces sp. CPCC 203577, an actinomycete soil isolate. The structures of 2 and 4 were elucidated as 1-hydroxy-7-oxolavanducyanin and Δ7″,8″-6″-hydroxynaphthomevalin, respectively, by 1D and 2D NMR. Antibacterial assays revealed that 2 had significant but reduced anti-Gram-positive bacterial activity compared with 1, and 4 was devoid of anti-Gram-positive bacterial activity. This indicated that the phenazinone nucleus in lavanducyanin and the monoterpene side chain in naphthomevalin might be important for their anti-Gram-positive bacterial activity. Compounds 1-4 were all inactive against Gram-negative bacteria.

Covering: up to July 2019 Terpene synthases (TSs) are responsible for generating much of the structural diversity found in the superfamily of terpenoid natural products. These elegant enzymes mediate complex carbocation-based cyclization and rearrangement cascades with a variety of electron-rich linear and cyclic substrates. For decades, two main classes of TSs, divided by how they generate the reaction-triggering initial carbocation, have dominated the field of terpene enzymology. Recently, several novel and unconventional TSs that perform TS-like reactions but do not resemble canonical TSs in sequence or structure have been discovered. In this review, we identify 12 families of non-canonical TSs and examine their sequences, structures, functions, and proposed mechanisms. Nature provides a wide diversity of enzymes, including prenyltransferases, methyltransferases, P450s, and NAD+-dependent dehydrogenases, as well as completely new enzymes, that utilize distinctive reaction mechanisms for TS chemistry. These unique non-canonical TSs provide immense opportunities to understand how nature evolved different tools for terpene biosynthesis by structural and mechanistic characterization while affording new probes for the discovery of novel terpenoid natural products and gene clusters via genome mining. With every new discovery, the dualistic paradigm of TSs is contradicted and the field of terpene chemistry and enzymology continues to expand.