Enantioselective Total Synthesis of Cotylenin A.

A convergent enantioselective total synthesis of cotylenin A is described. The A-ring fragment, prepared via the catalytic asymmetric intramolecular cyclopropanation developed in our laboratory, and the C-ring fragment, prepared from a known chiral compound via a modified acyl radical cyclization, were successfully assembled by the Utimoto coupling reaction. The formidable carbocyclic eight-membered ring of cotylenin A was efficiently constructed by a palladium-mediated cyclization.

Enantioselective approach to polycyclic polyprenylated acylphloroglucinols via catalytic asymmetric intramolecular cyclopropanation.

The formal enantioselective total synthesis of nemorosone, garsubellin A, clusianone, and hyperforin is described. The catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of an α-diazo ketone, a common synthetic intermediate for the above four polycyclic polyprenylated acylphloroglucinols previously reported by us, exhibited low enantioselectivity. However, CAIMCP of the corresponding α-diazo β-keto sulfone afforded the desired product in 79% yield with 84% ee.

Collective total synthesis of PPAPs: total synthesis of clusianone via intramolecular cyclopropanation.

The total synthesis of clusianone was accomplished through the stereoselective construction of a bicyclo[3.3.1]nonane derivative via a three-step sequence, which has been utilized for the total syntheses of nemorosone, garsubellin A, and hyperforin: intramolecular cyclopropanation, formation of a geminal dimethyl group, and regioselective ring opening of cyclopropane.

Stereoselective total synthesis of garsubellin A.

The stereoselective total synthesis of garsubellin A is described. The total synthesis was achieved through the stereoselective construction of a bicyclo[3.3.

Stereoselective total synthesis of nemorosone.

The highly stereoselective total synthesis of nemorosone via a new approach to the bicyclo[3.3.1]nonane-2,4,9-trione core which features intramolecular cyclopropanation of an α-diazo ketone, stereoselective alkylation at the C8 position, and regioselective ring-opening of cyclopropane is described.