^‡ These authors contributed equally This review covers the methods that chemists have developed to access halogenated polycyclic structures from polyenes, by emulating Nature’s enzymatic machineries. From pioneering studies to the most recent developments, the different strategies, whether based on the use of standard reagents or on the design of specific ones, will be presented. Finally, asymmetric reactions and applications for the total synthesis of natural products will be exposed. 1 Introduction 2 Pioneering Studies 3 Use of Specific Reagents 4 Use of N-Haloamides 5 Asymmetric Reactions 6 Total Synthesis of Halogenated Natural Products 7 Conclusion and Perspectives

Five different halofunctionalizations of acyclic monoterpenoids were performed using a combination of a hypervalent iodine(III) reagent and a halide salt. In this manner, the dibromination, the bromo(trifluoro)acetoxylation, the bromohydroxylation, the iodo(trifluoro)acetoxylation or the ene-type chlorination of the distal trisubstituted double bond occurred with excellent selectivity and moderate to good yields.

Social insects are in mutualism with microorganisms, contributing to their resistance against infectious diseases. The fungus Pseudallescheria boydii SNB-CN85 isolated from termites produces ovalicin derivatives resulting from the esterification of the less hindered site of the ovalicin epoxide by long-chain fatty acids. Their structures were elucidated using spectroscopic analysis and semisynthesis from ovalicin. For ovalicin, these compounds displayed antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei, with IC₅₀ values of 19.8 and 1.1 µM, respectively, for the most active compound, i.e., ovalicin linoleate. In parallel, metabolomic profiling of a collection of P. boydii strains associated with termites made it possible to highlight this class of compounds together with tyroscherin derivatives in all strains. Finally, the complete genome of P. boydii strains was obtained by sequencing, and the cluster of potential ovalicin and ovalicin biosynthesis genes was annotated. Through these metabolomic and genomic analyses, a new ovalicin derivative named boyden C, in which the 6-membered ring of ovalicin was opened by oxidative cleavage, was isolated and structurally characterized.