Synthesis of protoilludanes and related sesquiterpenes

Natural products continue to hold the interest and attention of a wide chemical community. This is due to their biological properties and potential applicability in health care and plant protection, as well as their frequently complex molecular architectures and arrays of functionality, which make them a challenge for total synthesis and a testing ground for novel methodology. These criteria are met to an extraordinary degree by protoilludanes, which are sesquiterpenes with a characteristic tricyclic 5/6/4-framework. The fortieth anniversary of the first protoilludane synthesis has now been taken as an occasion to review the main aspects of this fascinating class of compounds. Biosynthesis, biological properties and the unusually rich variety of synthetic approaches developed over the past forty years are discussed. About 80 different substitution patterns and 15 completed or uncompleted synthetic routes are listed in this review with the goal of providing a multifacetted picture of the changes in and development of synthetic philosophy and methodology from past to present.