A Divergent Approach to the Marine Diterpenoids (+)-Dictyoxetane and (+)-Dolabellane V.
We present a full account of the development of a strategy that culminated in the first total syntheses of the unique oxetane-containing natural product (+)-dictyoxetane and the macrocyclic diterpene (+)-dolabellane V. Our retrosynthetic planning was guided by both classical and nonconventional strategies to construct the oxetane, which is embedded in an unprecedented 2,7-dioxatricyclo[4.2.1.03,8]nonane ring system. Highlights of the successful approach include highly diastereoselective carbonyl addition reactions to assemble the full carbon skeleton, a Grob fragmentation to construct the 11-membered macrocycle of (+)-dolabellane V, and a bioinspired 4-exo-tet, 5-exo-trig cyclization sequence to form the complex dioxatricyclic framework of (+)-dictyoxetane. Furthermore, an unprecedented strain-releasing type I dyotropic rearrangement of an epoxide-oxetane substrate was developed.
Department of Chemistry and Pharmacy, Ludwig-Maximilians-University Munich, Butenandtstrasse 5-13, 81377, Munich, Germany.
Cedric L
CL
Hugelshofer
Department of Chemistry and Pharmacy, Ludwig-Maximilians-University Munich, Butenandtstrasse 5-13, 81377, Munich, Germany. thomas.magauer@lmu.de.
Thomas
T
Magauer
D001688:Biological Products; D003500:Cyclization; D004224:Diterpenes / Q000737:chemistry*; D004988:Ethers, Cyclic / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000737:chemistry*; D015394:Molecular Structure
D001688:Biological Products; D004224:Diterpenes; D004988:Ethers, Cyclic; D047028:Macrocyclic Compounds; C574909:dictyoxetane; C115566:dolabellane; C005287:oxetane
natural products; oxetane; rearrangements; terpenoids; total synthesis