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Total syntheses of the natural products kelsoene and preussin are comprehensively reviewed. Kelsoene is a sesquiterpene with a unique tricyclo[6.2.0.0^2,6]decane skeleton. It contains six stereogenic centers the selective construction of which has been addressed differently in the five syntheses known to date. Three syntheses employ an intermolecular [2+2]-photocycloaddition reaction as key step. One synthesis is based on a homo-Favorskii rearrangement and one on an intramolecular [2+2]-photocycloaddition. Preussin is a pyrrolidine alkaloid with three stereogenic centers which are all located within the central heterocyclic core (C-2, C-3, C-5). So far, 18 total syntheses of preussin have been completed. Seven syntheses include the nucleophilic attack on an l -phenylalanine derived electrophile as key step, five use α-amino- or α-hydroxycarboxylic acids as chiral pool building blocks. Two syntheses are based on sugars as chiral starting materials and two are based on the desymmetrization of meso -compounds. In addition, there are two syntheses which use a chiral auxiliary to establish the first stereogenic element en route to preussin.

Paraconic acids, belonging to the class of γ-butyrolactone natural products, display a broad range of biological activities such as antibiotic and antitumor properties. Consequently a great number of synthetic strategies have been devised for them, ranging from diastereoselective and chiral pool approaches to the application of asymmetric catalysis. This review gives a critical account on the different methods developed that lead to paraconic acids of great structural variety.

The isolation, structure and total synthesis of members of four classes of diterpenes has been summarized. Dolabellanes, neodolabellanes, dolastanes and neodolastanes are structurally related bi- or tricyclic diterpenes. Dolabellanes belong to a continuously growing class of diterpenes being isolated from marine and terrestrial sources. The published work on isolation and synthesis since 1998 has been summarized. Neodolabellanes represent a scarce class of diterpenes that have been isolated exclusively from marine sources. 5-7-6-tricyclic diterpenes classified as dolastanes have been isolated mainly from marine sources. The intense research devoted to the total synthesis of these diterpenes between 1986 and 1993 has been reviewed. Guanacastepenes have been isolated from fungi. These diterpenes are classified as neodolastanes and recently completed syntheses as well as synthetic approaches have been summarized.

Numerous biologically active macrocycles, including antibiotic, antifungal, and antitumor compounds, have been isolated from natural sources. In recent years the number of such structures has steadily increased, predominantly by polyketide- and peptide-derived compounds from various microorganisms. Macrocycles can combine the right amount of rigidity and flexibility and often exhibit unrivalled activity, thereby deviating from the current paradigm that medicinally active compounds should be small, nitrogen-rich heterocycles. Their challenging structures and intriguing activities have motivated organic chemists to find synthetic access to these compounds. Total synthesis plays a crucial role in the medicinal chemistry efforts towards macrocycles of already defined activity, as well as in the development of new and selective macrocyclization reactions. For lead discovery purposes, however, isolation or classical total synthesis may lack structural variability or prove to be too time consuming and impractical. A more rapid solution may be provided by diversity-oriented synthesis (DOS) of natural product-like molecules. A compromise between total synthesis and combinatorial chemistry, DOS concerns molecules displaying sufficient molecular complexity to resemble natural products, but features a more straightforward synthesis, thus allowing introduction of significant structural diversity. A brief review of flexible macrocyclization strategies and applications of DOS is given, as well as an overview of contributions to total and diversity-oriented synthesis of macrocycles from our laboratory.

α-Hydroxylated lignans, dimers of phenylpropene with important biological properties, have been enantioselectively prepared following different synthetic strategies. The early approaches to optically active α-hydroxylated lignans involved the use of chiral auxiliaries or were based on the stereoselective α-oxygenation of lactone lignan enolates. Most recently compounds from the pool of chiral building blocks, such as sugars or malic acid, became important starting materials for the asymmetric construction of α-hydroxylated lignans. The biaryl lignans schizandrin and isoschizandrin were obtained either by oxazoline-based biaryl coupling as key reaction or by asymmetric hydrogenation followed by stereoselective water addition. The preparation of furofuran lignans was achieved from dialkyl malates and tetrahydrofuran lignans were accessed from arabinose and xylose, respectively. Arabinose and malic acid, as well as unfunctionalized lactone lignans, prepared from chiral β-benzyl-γ-butyrolactones, were employed for the synthesis of α-hydroxylated lactone lignans. Further details of the strategies and an outlook for future investigations into methodology and interesting targets are provided in this review.