ChemInform Abstract: Synthetic Approaches to Antiinflammatory Macrolactones of the Oxacyclododecindione Type.

A variety of attempts to synthesize oxacyclododecindione macrolactones through carbonylative ring-closure, intramolecular alkyne hydroacyalation, and Ru-catalyzed double bond isomerization fails.

ChemInform Abstract: Radical Addition to Iminium Ions and Cationic Heterocycles

Carbon-centered radicals represent highly useful reactive intermediates in organic synthesis. Their nucleophilic character is reflected by fast additions to electron deficient C=X double bonds as present in iminium ions or cationic heterocycles. This review covers diverse reactions of preformed or in situ-generated cationic substrates with various types of C-radicals, including alkyl, alkoxyalkyl, trifluoromethyl, aryl, acyl, carbamoyl, and alkoxycarbonyl species. Despite its high reactivity, the strong interaction of the radical’s SOMO with the LUMO of the cation frequently results in a high regioselectivity. Intra- and intermolecular processes such as the Minisci reaction, the Porta react…

Total synthesis of two potent anti-inflammatory macrolactones of the oxacyclododecindione type

An esterification/Friedel-Crafts-cyclization approach permitted the first successful synthetic entry into the oxacyclododecindione subclass of the dihydroxyphenylacetic acid lactone-type natural products. This route allowed the preparation of two highly active anti-inflammatory fungal secondary metabolites 14-deoxyoxacyclododecindione and 14-deoxy-4-dechlorooxacyclododecindione as well as their 14-desmethyl analogues.

ChemInform Abstract: A High-Yielding Modular Access to the Lamellarins: Synthesis of Lamellarin G Trimethyl Ether (Ia), Lamellarin η (II) and Dihydrolamellarin η (Ib).

A surprising switch in absolute configuration of anti-inflammatory macrolactones.

Oxacyclododecindione-type macrolactones exhibit highly potent anti-inflammatory activities even at nanomolar concentration. After the determination of the relative configuration of the stereocenters at C14 and C15 by total synthesis of 4-dechloro-14-deoxyoxacyclododecindione and 14-deoxyoxacyclododecindione, the absolute configuration has now been assigned by X-ray crystallography. Surprisingly, the absolute configuration is (14S,15R) which differs for C15 from that of the well-known derivatives of (S)-curvularin. The biological activities of both enantiomers of 14-deoxyoxacyclododecindione, obtained by racemic synthesis and optical resolution, were investigated and the ring conformation of…

Synthetic Approaches to Anti-Inflammatory Macrolactones of the Oxacyclododecindione Type

Various synthetic approaches to the oxacyclododecindione-type macrolactones, known for their potent anti-inflammatory activity, are presented. These include an attempted carbonylative ring closure, a hydroacylation route, and an approach by ring-closing metathesis and double bond isomerization, as well as a strategy including ring-closing metathesis/unsaturation. The last route allowed the preparation of a bioactive analogue of the recently described 14-deoxyoxacyclododecindione.

Synthetic Approaches to the Lamellarins—A Comprehensive Review

The present review discusses the known synthetic routes to the lamellarin alkaloids published until 2014. It begins with syntheses of the structurally simpler type-II lamellarins and then focuses on the larger class of the 5,6-saturated and -unsaturated type-I lamellarins. The syntheses are grouped by the strategy employed for the assembly of the central pyrrole ring.

Correction: Total synthesis of two potent anti-inflammatory macrolactones of the oxacyclododecindione type

Correction for ‘Total synthesis of two potent anti-inflammatory macrolactones of the oxacyclododecindione type’ by Johannes Tauber et al., Org. Biomol. Chem., 2015, 13, 7813–7821.

A high-yielding modular access to the lamellarins: synthesis of lamellarin G trimethyl ether, lamellarin η and dihydrolamellarin η.

CCDC 1454207: Experimental Crystal Structure Determination

Related Article: Johannes Tauber, Markus Rohr, Thorsten Walter, Dieter Schollmeyer, Karin Rahn-Hotze, Gerhard Erkel, Till Opatz|2016|Org.Biomol.Chem.|14|3695|doi:10.1039/C6OB00430J