Cp₂TiCl-Mediated Reductive Cyclization: Total Synthesis of Pestalotiolactone A, Myrotheciumone A, and Scabrol A

Abstract

The first stereoselective total syntheses of fungal secondary metabolites monoterpenoid (+)-pestalotiolactone A, meroterpenoid (−)-myrotheciumone A, and iridoid lactone (+)-scabrol A have been accomplished in an expedient unified approach starting from D-(+)-malic acid employing an epoxide opening-radical cyclization protocol initiated by Cp 2 Ti(III)Cl as a key step to assemble the core bicyclic lactone moieties of these molecules with complete diastereoselective control. Finally, the deoxygenation and methylation delivered the target natural products.

Total Synthesis of Terpenes and Their Biological Significance: A Critical Review

“…This is the first time that (±)-α-ekasantalic acid (201) has been synthesized entirely. In the whole synthesis of α-santalene (202), as a target molecule, the compound ( 200) is a recognized precursor to synthesizing significant active molecules (Scheme 15) [92].…”

“…Epoxide (704) was exposed to titanocene-(III)-chloride to obtain the desired diol (705) as a single diastereoisomer. Diol (705) was then reacted with O-phenyl chlorothiono formate and C 5 H 5 N at 0 • C to r.t. to synthesize xanthate (706) in a 59% yield (two steps) from the epoxide (704), undergoing deoxygenation with AIBN as radical accelerator and (TMS) 3 SiH as H 2 origin for 1 h at 80 • C to deliver the product myrotheciumone A (707), as colorless crystals in an 85% yield (Scheme 42) [202].…”

Catalyst-controlled site-selective methylene C–H lactonization of dicarboxylic acids

“…4). Myrotheciumone A 64 (34), a target recently completed by Begum and co-workers (35), is a bicyclic cytotoxic lactone isolated from the fungus Ajuga decumbens that possesses the bicyclic 5,5-fused scaffold as in lactone 25b (Fig. 3A).…”

“…4). Myrotheciumone A ( 64 ) ( 34 )—a bicyclic cytotoxic lactone isolated from the fungus Ajuga decumbens and recently synthesized by Begum and Chakraborty ( 35 )—possesses the bicyclic 5,5-fused scaffold as in lactone 25b (Fig. 3A).…”