A Divergent Approach to the Marine Diterpenoids (+)‐Dictyoxetane and (+)‐Dolabellane V

Abstract

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[4.2.1.0 ]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.

Total Synthesis of (−)-Mitrephorone A

“…Although in synthetic endeavors to taxol accessing the oxetane is tangential, there are numerous other targets, wherein installation of the oxacycle is central to the synthesis strategy. These include thromboxane A 2 , oxetanocin A, oxetin, merrilactone A, and more recently dictyoxetane . Isolated in 2005 by Oberlies and co-workers from the Bornean shrub Mitrephora glabra , (−)-mitrephorone A ( 1 ) contains a fully substituted oxetane embedded in a pentacyclic carbon skeleton (Scheme ).…”

Marine natural products

“…328 Dolastane diterpenes from Canistrocarpus cervicornis inhibited HIV-1, 329 and spartane diterpenes from Stoechospermum marginatum induced apoptosis in melanoma cells. 330 The rst total synthesis of dictyoxetane 331,332 and the unnatural enantiomer (À)-erogorgiaene, 333 were reported. Additionally, there were many papers dealing with the biological properties of brown algal lipids, [334][335][336][337] polyphenolics [338][339][340][341][342][343][344][345][346][347][348] and carotenoids.…”

Oxetanes and Oxetenes: Fused-Ring Derivatives

“…162 Magauer reported the very first synthesis of (+)-dictyoxetane in 2016. 163,164 The challenging oxetane in 226 was constructed through the intramolecular displacement of an allylic mesylate, generated from 225, under basic conditions in 88% yield. Shen reported the isolation of phomopsidone A in 2014 from the mangrove endophytic fungus Phomopsis sp.…”