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.

Rosellin A and B, two red diketopiperazine alkaloids with unprecedented structures, have been isolated from the fruiting bodies of the mushroom Mycena rosella. The structures of the rosellins were mainly deduced from their 2D NMR and HRMS (ESI) spectra. Their absolute configuration was determined by comparison of the CD spectra of the rosellins with the corresponding CD spectra obtained by quantum chemical calculations. Root exposure to rosellin A led to bleaching of the leaves of Lepidium sativum plants.

Four new hygrophorones (1–4) together with the known hygrophorone B12 (5) have been isolated from fruiting bodies of the basidiomycete Hygrophorus abieticola Krieglst. ex Gröger & Bresinsky. Their structures were assigned on the basis of extensive one and two dimensional NMR spectroscopic analyses as well as ESI-HRMS measurements. Among these compounds, two previously undescribed hygrophorone types, named hygrophorone H12 (3) and 2,3-dihydrohygrophorone H12 (4), were identified. The absolute configuration of hygrophorone E12 (2) is suggested based on quantum chemical CD calculations, while a semisynthetic approach in conjunction with computational studies and analysis of NOE interactions allowed the stereochemical assignment of compounds 3 and 4. Additionally, semisynthetic derivatives of hygrophorone B12 (5) were generated by acetylation of the hydroxyl groups. The biological activity of the natural and semisynthetic hygrophorones was evaluated against phytopathogenic organisms, revealing that the α,β-unsaturated carbonyl functionality is likely to be an essential structural feature. Hygrophorone B12 (5) was identified as the most active compound, acting against both ascomycetous fungi and oomycetes.

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.

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.

Takai–Utimoto reactions with secondary and tertiary aliphatic halides usually failed according to previous reports. Now, significant improvements could be achieved, and especially secondary aliphatic halides can be coupled to aromatic aldehydes in yields of up to >95%. A variety of processes are competing with the desired one, and thus conditions must be adapted to the nature of the aldehyde as well as the aliphatic halide used, as the outcome of these reactions is strongly affected by the putative radical intermediates.

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.

8-Prenylnaringenin, a flavonoid, is the strongest known phytoestrogen (plant derived estrogen mimic) used in phytomedicinal applications. Starting from xanthohumol a byproduct of hops-extraction, 8-prenylnaringenin can be synthesized via isoxanthohumol. Of various demethylation procedures tested, the best yield (92%) is obtained by treatment with scandium trifluoromethanesulfonate and potassium iodide without any need of protection. The demethylation with AlBr3/collidine and of the TIPS protected isoxanthohumol provides good results too.