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.

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.

The spirodioxolactone ochroleucin A1 (1 ) is responsible for the red colour produced when the stalk base of Russula ochroleuca and R. viscida is treated with aqueous KOH. The labile chromogen rearranges easily into the isomeric dilactoneochroleucin A2 (2 ). Ochroleucin A1 is accompanied by the biosynthetically related hemiacetal ochroleucin B (5 ). The new compounds, whose structures were established by MS and NMR methods, appear to be derived biosynthetically by oxidative condensation of two monomeric units. One of them, 2,5‐dihydroxy‐4‐(3‐methylbut‐3‐en‐1‐ynyl)benzaldehyde (6 ), was detected in the crude toadstool extract by GC/MS comparison with a synthetic sample. The absolute configurations of the ochroleucins A1 and B have been determined by quantum chemical calculation of their CD spectra.

A class of enantiopure β‐seleno amide palladium complexes catalyze the microwave‐accelerated enantioselective allylic alkylation of rac ‐1,3‐diphenyl‐2‐propenyl acetate with different malonates. Good yields and enantiomeric excess values of up to 94 % ee were obtained after irradiation times of 2 or 4 min.

A new series of enantiopure oxazolidine‐thioether and thiazolidine‐alcohol ligands have been synthesized from L ‐cysteine, S‐methyl‐L ‐cysteine, and L ‐methionine in a straightforward manner that allows numerous structural variations to be formed. These types of ligands have not previously been used in asymmetric palladium‐catalyzed allylations and their efficacy was explored in the reaction of rac‐1,3‐diphenyl‐2‐propenyl acetate with dimethyl malonate. The reaction proceeds in excellent yield and with good enantioselectivity. The palladium catalyst derived from N‐benzyl‐2,2‐dimethyl‐4‐(2‐thiapropyl)oxazolidine (12 ) provides the allylation product in a quantitative yield and with an enantiomeric excess of 94%.

A series of 16 different 3‐acyloxy methyl ketones, the acyloin acetates and butyrates (±)‐5 , was synthesised by a straightforward new method through alkylation of tert‐butyl 2‐acyloxyacetoacetates 3 , followed by chemoselective dealkoxycarbonylation of the tert‐butyloxycarbonyl group in the presence of other ester groups. Subsequent hydrolysis of (±)‐5 can be achieved with base to give racemic acyloins 6 , or with lipase catalysis to afford the corresponding non‐racemic acyloins (S )‐6 . The remaining (R )‐acyloin esters 5 can be racemised and resubjected to the procedure, or hydrolysed chemically. The kinetic resolution with two of the six tested enzymes, CAL‐B and BCL (PS) lipase, proceeded selectively [enantiomeric ratio (E ) values between 50 and > 200] and most of the acyloins (S )‐6 were obtained in very high enantiomeric excesses (up to > 99% ee ).