Hypericum perforatum L. commonly known as Saint John’s Wort (SJW) is an economically important medicinal plant known for accumulating its valuable bioactive compounds in a compartmentalized fashion. The dark glands are very rich in hypericin, and translucent glands are filled with hyperforin. The antibiotic properties of the afore mentioned bioactive compounds make it hard to establish tissue regeneration protocols essential to put in place a transformation platform that is required for testing gene function in this challenging species. In this study, we report the establishment of a regeneration and root induction cycle from different types of explants. The regeneration cycle was set up for the continuous supply of roots and leaf explants for downstream transformation experiments. The most effective medium to obtain multiple shoot-buds from node cultures was MS (Murashige and Skoog, Physiol Plant 15:473–497, 1962) medium supplemented with 0.5 mg L−1 6-Benzylaminopurine (BAP) and 0.5 mg L−1 indole-3-butyric acid (IBA). The same combination yielded copious amounts of shoots from root and leaf explants as well. For rooting the elongated shoots, MS medium devoid of plant growth regulators (PGRs) was sufficient. Nevertheless, addition of a low amount of IBA improved the quantity and quality of roots induced. Additionally, the roots obtained on a medium containing IBA readily developed shoot buds.

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The replacement of the disulfide bridge by other types of side chain linkages has been a continuous endeavor in the development of cyclic peptide drugs with improved metabolic stability. Octreotide is a potent and selective somatostatin analog that has been used as an anticancer agent, in radiolabeled conjugates for the localization of tumors and as targeting moiety in peptide-drug conjugates. Here, we describe an onresin methodology based on a multicomponent macrocyclization that enables the substitution of the disulfide bond by a tertiary lactam bridge functionalized with a variety of exocyclic moieties, including lipids, fluorophores, and charged groups. Conformational analysis in comparison with octreotide provides key information on the type of functionalization permitting the conformational mimicry of the bioactive peptide.

Although stripped from hydroxyl-groups, deoxygenated hygrophorones remain highly active against severe phytopathogens. The synthesis to these natural product congeners is achieved in rearrangement sequences, with an optimized deprotection strategy avoiding retro-aldol reactions. The activities are comparable to fungicides used in agriculture. Based on naturally occurring hygrophorones, racemic di- and mono-hydroxylated cyclopentenones bearing an aliphatic side chain have been produced in short synthetic sequences starting from furfuryl aldehyde. For the series of dihydroxylated trans-configured derivatives, an Achmatowicz-rearrangement and a Caddick-ring contraction were employed, and for the series of trans-configured mono-hydroxylated derivatives a Piancatelli-rearrangement. All final products showed good to excellent fungicidal activities against the plant pathogens B. cinerea, S. tritici and P. infestans.

Four new 11‐mer peptaibols, named albupeptins A–D (1–4), were isolated from cultures of the fungus Gliocladium album. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy, as well as ESI‐HRMSn analysis. The sequence of albupeptin A (1) was thus identified as Ac‐Aib1‐Aib2‐Val3‐Leu4‐Aib5‐Pro6‐Iva7‐Leu8‐Gln9‐Aib10‐Leuol11. Albupeptins B (2) and C (3) feature an exchange of Aib5 by Iva5 and of Aib1 by Iva1, respectively, and albupeptin D (4) contains both Iva1 and Iva5 residues. The stereochemistry of the isolated peptaibols 1–4 was unambiguously assigned by 1H NMR chemical shift analysis in conjunction with solid‐phase peptide synthesis. By using this approach, the absolute configuration of the Iva residues in albupeptins A (1) and C (3) was determined to be D, whereas albupeptins B (2) and D (4) feature an additional Iva5 residue with an L configuration. Thus, albupeptins B (2) and D (4) belong to the rare class of peptaibols that have both stereoisomers of Iva in the same sequence.

Hygrophorone B12, a new antifungal constituent from the fruiting bodies of Hygrophorus abieticola, has been isolated and subsquently synthesized in enantiomerically pure form. The total synthesis includes a Sharpless asymmetric dihydroxylation protocol as the stereodifferentiating step, followed by two diastereoselective aldol‐type reactions. The approach allows the unambiguous control of all three stereogenic centres, and, furthermore, unequivocal determination of the relative and absolute configuration of antibiotic hygrophorones B for the first time.

Benzophenanthridine alkaloids are strong antimicrobials of Papaveraceae and attractive lead compounds for drug development. The cytotoxicity of these compounds requires the producing plant to limit the pathogen-triggered burst of biosynthesis. Cells of Eschscholzia californica excrete early benzophenanthridines to the cell wall, followed by re-uptake and reduction in the cytoplasm by the detoxifying enzyme sanguinarine reductase. We now discovered that this enzyme is a core component of self-control in alkaloid production. RNAi-based silencing of sanguinarine reductase gave rise to mutants that either show a complete stop of elicitor-triggered alkaloid production or a burst of biosynthesis that severalfold surpasses the wild type level. These unexpected phenotypes reflect impacts of substrate or product of sanguinarine reductase: the substrate, sanguinarine, inhibits phospholipase A2 at the plasma membrane, an initial component of the signal path towards expression of biosynthetic enzymes. The product, dihydrosanguinarine, inhibits enzymes of early biosynthesis, prior to reticuline formation. By tuning these steady states, sanguinarine reductase adjusts the capacity of alkaloid biosynthesis: a minimum activity is sufficient to prevent the blockade of the induction pathway by sanguinarine, while the full activity of the same enzyme causes a limitation of the biosynthetic flow via dihydrosanguinarine.

This review discusses the use of various isocyanides (regular, chiral, and convertible) in asymmetric multicomponent reactions. In particular, stereoselective Ugi and Passerini reactions are highlighted, as well as their applications in modular sequential reactions and natural product synthesis.Isocyanide‐based multicomponent reactions (IMCRs) can be considered one of the breakthrough reaction classes of the last century. Moreover, asymmetric IMCRs have recently developed into powerful reactions for the versatile synthesis of highly complex molecules. The progress made in the development of stereoselective Passerini and Ugi reactions has led to the advancement of catalytic asymmetric IMCRs. This review gives an overview of recent advances in the field of asymmetric IMCRs with a focus on stereoselective α‐additions of isocyanides. In addition, the use of convertible isocyanides in stereoselective cascade IMCRs is covered and future opportunities and potential applications of (asymmetric) IMCRs are briefly discussed.

Isonitrile‐functionalized biaryl ethers can serve as key building blocks for the highly efficient one‐step production of natural product inspired‐macrocycles, with six or even twelve new bonds and rings with up to 50 members being formed in total yields of up to 51 %. Aliphatic diamine and diacid tethers give access to two different classes of N ‐substituted biaryl ether cyclopeptides, suitable for library construction. As part of a conceptual work on MiBs (m ultiple m ulticomponent m acrocyclizations/m acrocycles i ncluding b ifunctional b uilding b locks), the influence of length and type of flexible tethers on the propensity for cyclization is studied.