Total Syntheses of Highly Oxidized ent-Kaurenoids Pharicin A, Pharicinin B, 7-O-Acetylpseurata C, and Pseurata C: A [5+2] Cascade Approach

Abstract

The unprecedented oxidative dearomatization-induced [5+2] cycloaddition/pinacol-type 1,2-acyl migration cascade efficiently generates a quaternary carbon center and assembles the highly oxygenated bicyclo[3.2.1]octane framework of ent-kaurene diterpenoids. By incorporation of the subsequent retro-aldol/aldol process and singlet oxygen ene reaction, this concise and convergent approach has enabled the first asymmetric total syntheses of pharicin A, pharicinin B, 7-O-acetylpseurata C, and pseurata C.

Strategies to diversify natural products for drug discovery

“…Once new molecules with attractive biological activity are isolated from natural resources and structurally characterized, they can be considered for target-oriented synthesis that can be planned effectively with retrosynthetic analysis. [262][263][264] The elaborated divergent total synthesis accesses a complex target or even a collection of targets for the straightforward preparation of natural products and their anlogues, 260,261 as exemplified by the synthetic efforts on compound 1. 265 It can work as an alternative source of many valuable natural products and relieve the supply crisis from limited natural resources, although the synthetic yield sometimes may be poor.…”

A Synthetic Approach Toward a Brominated Oxocane Labdane Diterpenoid Isolated From Laurencia obtusa

“…The oxocane ring might be constructed by RCM of the diene 6, which in turn might be obtained by installation of two olefinic side chains into the Wieland-Miescher ketone derivative 7. 11 Although the hydroxyketone 12 is a known compound derived from Wieland-Miescher ketone (8) and was employed as a starting material for synthetic studies of several natural products, [12][13][14] we took an alternative Wieland-Miescher ketone derivative 7 as our starting material, which is easy to obtain in high enantiomeric excess (Scheme 2). 11 Regioselective protection of the carbonyl group at C9 of the ketone 7 was carried out simply with ethylene glycol in the presence of a catalytic amount of dcamphorsulfonic acid without employing solvent under reduced pressure at 40°C.…”

Total Syntheses of Rhodomolleins XX and XXII: A Reductive Epoxide‐Opening/Beckwith–Dowd Approach

“…[7] However,attempts to access the cycloheptane-fused cycloadduct 7 were met with disappointing results (for details,s ee the Supporting Information). Initially,w ea ssumed that the bicyclo[3.2.1]octane carbon framework of 5 and 6 could be built up from vinylphenol 8 according to our previously developed ODI-[5+ +2] cascade (path a).…”

“…On the other hand, apart from few examples of cascade strategies, [4] theconstruction of the [3.2.1] bicyclicskeletons in the total syntheses of tetracyclic diterpenoids required multistep reaction sequences, [5] which inevitably maximized functional group manipulations and resulted in lengthier synthetic routes.P rompted by this problem, we sought to develop versatile protocols by establishing the [3.2.1] bicyclic motif in am ore straightforward manner.R ecently,i nspired by the oxidative dearomatization-induced (ODI) cycloaddition/ring distortion approaches toward the syntheses of diterpenoid alkaloids, [6] we reported an ODI-[5+ +2] cycloaddition/pinacoltype 1,2-acylm igration cascade reaction, leading to the concise total syntheses of several highly oxidized ent-kauranoids. [7] In continuation of our work in this area, we herein describe the first total syntheses of rhodomolleins XX (5)and XXII (6), two congeners of the grayanoid family,w hich are isolated from Rhododendron molle G. Don (Ericaceae), [8] through an ew titanium(III)-mediated reductive epoxideopening/Beckwith-Dowd rearrangement process.…”

“…Initially,w ea ssumed that the bicyclo[3.2.1]octane carbon framework of 5 and 6 could be built up from vinylphenol 8 according to our previously developed ODI-[5+ +2] cascade (path a). [7] However,attempts to access the cycloheptane-fused cycloadduct 7 were met with disappointing results (for details,s ee the Supporting Information). Based on the elegant work of Baran [9a] and Mori, [9b] an alternative strategy relying on the regioselective fragmentation of an excessively functionalized intermediate [10] was proposed (path b).…”