Maytansinol is a valuable precursor for the preparation of maytansine derivatives (known as maytansinoids). Inspired by the intriguing structure of the macrocycle and the success in targeted cancer therapy of the derivatives, we explored the maytansinol acylation reaction. As a result, we were able to obtain a series of derivatives with novel modifications of the maytansine scaffold. We characterized these molecules by docking studies, by a comprehensive biochemical evaluation, and by determination of their crystal structures in complex with tubulin. The results shed further light on the intriguing chemical behavior of maytansinoids and confirm the relevance of this peculiar scaffold in the scenario of tubulin binders.

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Dedicated to Professor Franco Cozzi on the occasion of his 70th birthday.Asymmetric allylation represents an important reaction applied in the natural product synthesis. The stereoselective introduction of an allyl group allows to obtain versatile chiral building blocks, which may further undergo various transformations due to the presence of the carbon-carbon double bond. In this review, we address the Brown allylation, which involves the conversion of aldehydes into homoallylic alcohols using Ballyldiisopinocampheylborane as a chiral reagent. We provide a comprehensive overview of the reaction and highlight its application in the synthesis of natural products, while assessing its performance in comparison to other approaches. The total of 17 syntheses have been described, including the synthesis of biologically active macrolides disciformycin B, biselyngbyolide B, peloruside A, and gliomasolide A, bis-piperidine alkaloid (À )anaferine and dysoxylactam A.

Imidazopyrimidines with diverse substitution patterns are a prime class of heterocycles, present in many commercially available or late‐stage clinical trials drugs. Here, we describe a fast access to diaminoimidazopyrimidines by means of a powerful multicomponent reaction; the Groebke–Blackburn–Bienaymé reaction. We provide the design of such libraries of compounds, identifying all the structural motifs, and subsequently their synthesis. Scope and limitations are discussed, in addition to data mining in the Cambridge Structural Database and pharmacophore search with Crossminer. The presented approach highlights the vast amount of data available in the databases and provides potential future scaffold hopping alternatives for compounds with similar binding patterns. Further studies are ongoing to introduce more “drug‐like” properties into this scaffold and to investigate cellular mechanism‐based anti‐cancer behaviours.

Invited for the cover of this issue are the groups of Professors Passarella and Pieraccini at the University of Milan, in collaboration with some of the members of TubInTrain consortium. The image depicts work with the elements of nature, in particular the destabilising effect of maytansinol (the constellation) on microtubules (the trees). Read the full text of the article at 10.1002/chem.202203431.