Stereoselective and Modular Assembly Method for Heterocycle‐Fused Daucane Sesquiterpenoids

Abstract

A stereoselective synthetic method is reported for the molecular framework found in common daucane and isodaucane sesquiterpenoid natural products. The synthetic method constitutes a scalable, modular, and also asymmetric access to a complex natural product scaffold, wherein the substitution pattern and the stereochemistry can be adjusted simply by choosing different starting materials. The method allows the rapid introduction of diverse heterocyclic substructures such as (benzo)furans, (benzo)thiophenes, dithiins, thiazoles, and indoles, which actually also facilitate and direct the key intramolecular annulation step.

The Biosynthesis of Norsesquiterpene Aculenes Requires Three Cytochrome P450 Enzymes to Catalyze a Stepwise Demethylation Process

“…From these S. cerevisiae expression results,t hree new asperaculanes (10)(11)(12), all without the C-14 hydroxy group, were characterized. Ther esults establish that AneF oxidizes C-12 to ac arboxylate,A neG hydroxlates C-2, and AneD hydroxylates C-10.…”

“…[9] Thus, an umber of total syntheses of daucane sesquiterpenes have been reported. [10] Arecently discovered (À)-daucane-derived herbicide,a spterric acid, that inhibits dihydroxy acid dehydratase in plant catabolism, further highlights the importance of this class of sesquiterpenes. [11] Aspergillus aculeatus is ap rolific producer of secondary metabolites and industrial enzymes.…”

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

“…The scope of the dihydrodithiin-based allyl cation cycloadditions can be appreciated by the relative ease with which it allowed the assembly of complex terpenoid frameworks. Examples from our research group include various daucanoid and kauranoid terpene scaffolds such as 108 , 109 , and 110 , which can be assembled from dihydrodithiin 3 as a building block in just a few synthetic operations with good to excellent control of the relative stereochemistry ( Scheme 17 ) [ 108 – 109 ].…”

Recent Advances in Transition-Metal-Free (4+3)-Annulations

“…99 More recently, work towards the daucane sesquiterpenoid skeleton used TFA in CH 2 Cl 2 to generate the desired cycloadduct in excellent yield and as a single diastereomer (Scheme 5.2.1, b). 100 Furthermore, heterocycles other than furan could be incorporated using this method. In work towards the synthesis of the giberellane and kauranoid scaffolds, Ga(OTf) 3 (20 mol%) or TFA (2 equiv) could be used in CH 2 Cl 2 to afford the desired cycloadducts, but in poor diastereoselectivities (Scheme 5.2.1, c).…”

“…101,102 These examples illustrate that both solvent and acid play subtle roles in the reaction. Scheme 5.2.1 Examples of intramolecular (4+3)-annulations towards the synthesis of the natural product scaffolds of: (a) rameswaralide, 99 (b) daucanes, 100 (c) gibberellane and kauranoids 101,102 It is evident that although numerous strategies exist to synthesize the 5,7,6-fused-ring scaffold, interest in preparing liphagal and frondosin B remains strong. Xue and Li…”