A Synthetic Route to The Core Structure of (−)-Retigeranic Acid A

Abstract

Retigeranic acid A is a uniquely structured pentacyclic sesterterpene bearing eight stereogenic centers. We report a concise route to the core structure of (−)-retigeranic acid A. The stereochemistry of its six chiral centers and three quaternary carbon centers was well-controlled. This route features two intramolecular Pauson–Khand reactions (IMPKRs): the first forged the D and E rings to deliver the triquinane subunit, and the second constructed the A and B rings and diastereoselectively installed the quaternary C6a center.

Recent Advances in Non-Precious Metal Catalysis

“…Initial attempts using Co 2 (CO) 8 as a catalyst under a CO atmosphere resulted in variable yields. Interestingly, the annulation reaction performed effectively in good and reproducible yields when a catalytic amount of CoBr 2 (10 mol %) was applied to build challenging D and E rings containing three stereogenic centers, including a quaternary stereocenter (Scheme 53 amount of Co 2 (CO) 8 for the construction of the A and B rings, which were obtained in good yield and 2:1 dr. 107 Related to the 2 + 2 + 1 cyclization motive of Pauson− Khand, several cobalt-mediated 2 + 2 + 2 reactions have been studied recently with a focus on mechanistic insight into the transformation reported in a collaborative work between Vollhard and Houk. 108 A detailed DFT study on the Cocatalyzed intramolecular cycloisomerization of allylic ethers containing α,δ,ω-enynenes to provide 3-(oxacyclopentyl or cycloalkyl)furans (Scheme 54) indicated the initial stereoselective complexation of the triple bond with one of the double bonds, which was then followed by a rate-determining oxidative coupling to a triplet 16e cobalta-2-cyclopentene.…”

“…Interestingly, the annulation reaction performed effectively in good and reproducible yields when a catalytic amount of CoBr 2 (10 mol %) was applied to build challenging D and E rings containing three stereogenic centers, including a quaternary stereocenter (Scheme ). The synthesis then proceeded with further elaboration by a second intramolecular Pauson–Khand employing a stoichiometric amount of Co 2 (CO) 8 for the construction of the A and B rings, which were obtained in good yield and 2:1 dr …”

A Modular Approach to Angularly Fused Polyquinanes via Ring-Rearrangement Metathesis: Synthetic Access to Cameroonanol Analogues and the Basic Core of Subergorgic Acid and Crinipellin

“…However, most of these methods involve a large number of linear steps even to construct the basic natural product skeleton starting from the acyclic/cyclic precursors. A few groups, including Paquette, Schore, Wender, Mehta, Curran, Cook, Piers, Moore, Lee, Srikrishna, Yang, and others, significantly contributed to the synthesis of angularly fused polyquinanes. Surprisingly, a few reports involving metathetic approaches such as ring-closing metathesis (RCM), sequential ring-opening metathesis (ROM)–ring-closing metathesis (RCM), and ring-rearrangement metathesis (RRM) as key steps were found, including by our group .…”

Enantiocontrolled Total Synthesis of (−)-Retigeranic Acid A

“…The above distinct profile makes retigeranic acid A ( 1 ) an appealing synthetic target, toward which a number of innovative methodologies and tactics have been developed. , In 1985, Corey and co-workers accomplished a landmark racemic synthesis of 1 featuring a Diels–Alder reaction, [2 + 2] cycloaddition, and ring expansion . By utilizing a sequential double Claisen–Schmidt condensation as the key transformation, Paquette and co-workers achieved the first asymmetric total synthesis of (−)- 1 in 1987. , Shortly after that, the Hudlicky group disclosed an impressive vinylcyclopropane-cyclopenane rearrangement approach to (−)- 1 in 1989 .…”