Asymmetric syntheses of (+)- and (–)-collybolide enable reevaluation of kappa-opioid receptor agonism

The fungal metabolite collybolide attracted attention as a non-nitrogenous, potent and biased agonist of the kappa-opioid receptor (KOR). Here we report a 10-step asymmetric synthesis of this complex sesquiterpene that enables facile access to either enantiomer. The synthesis relies on a diastereoselective α-benzoyloxylation to install the buried C6 benzoate and avoid irreversible translactonization of the congested, functionally dense core. Neither enantiomer, however, exhibited KOR agonism, indicating that collybolide has been mischaracterized as a KOR agonist and leaving open the basis for antipruritic effects in mice.

Manganese (I)-Catalyzed Access to 1,2-Bisphosphine Ligands

Chiral bisphosphine ligands are of key importance in transition-metal-catalyzed asymmetric synthesis of optically active products. However, the transition metals typically used are scarce and expensive noble metals, while the synthetic routes...

Asymmetric Synthesis of Isochromanone Derivatives via Trapping Carboxylic Oxonium Ylides and Aldol Cascade

An efficient asymmetric synthesis of isochromanone derivatives was realized through Z-selective-1,3-OH insertion/aldol cyclization reaction involving acyclic carboxylic oxonium ylides. The combination of achiral dirhodium salts and chiral N,N’-dioxide-metal complexes, along...

Organocatalytic asymmetric synthesis of multifunctionalized α-carboline-spirooxindole hybrids that suppressed proliferation in colorectal cancer cells

Organocatalytic asymmetric [3 + 3] annulations of isatin-derived MBH carbonates and indolin-2-imines have been efficiently achieved. This appears to be the first enantioselective approach to use isatin-derived MBH carbonates as...

Asymmetric Synthesis of Isoxazole and Trifluoromethyl‐Containing 3,2’‐Pyrrolidinyl Dispirooxindoles via Squaramide‐Catalysed [3 + 2] Cycloaddition Reactions

A highly efficient squaramide‐catalysed asymmetric domino Michael/Mannich [3 + 2] cycloaddition of 3‐methyl‐4‐nitro‐5‐ isatylidenyl‐isoxazoles and N‐2,2,2‐trifluoroethylisatin ketimines was developed. A new class of complex and skeletondiversified isoxazole and trifluoromethyl‐containing 3,2’‐pyrrolidinyl...

Asymmetric Synthesis of Tetrasubstituted Cyclic Amines via Aza-Henry Reaction using Cinchona Alkaloid Sulfonamide/Zinc(II) Catalysts

The first enantioselective aza-Henry reaction of non-activated cyclic iminoesters, derived from cyclic amino acids, has been developed. Good yields and enantioselectivities were observed for the reaction using our original cinchona...

Organocatalytic Atroposelective Construction of Axially Chiral Nonsymmetric Biaryltriols and Their Applications on Asymmetric Synthesis and Heavy Metal Ion Detection

An organocatalytic methodology toward the atroposelective construction of axially chiral nonsymmetric biaryltriols has been successfully developed. Quinine-derived thiourea-catalyzed intramolecular reaction through VQM (vinylidene ortho-quinone methides) intermediate enabled efficient access to...