Short and Efficient Synthetic Route to Methyl α-Trioxacarcinoside B and Anomerically Activated Derivatives

A 9-step synthetic route to the complex carbohydrate methyl α-trioxacarcinoside B from 2-acetylfuran is described. Anomerically activated forms, including 1-phenylthio, 1-O-(4′-pentenyl), 1-fluoro, and 1-O-acetyl derivatives are also prepared

Total Synthesis of the Leucosceptroid Family of Natural Products

A highly efficient strategy enabled the asymmetric total synthesis of 15 antifeedant leucosceptroid natural products. The advanced tricyclic core, available in gram quantity, served as the pivotal intermediate for the preparation of norleucosceptroids B, C, F, and G and leucosceptroids A, B, G, I, J, L, and M. Additionally, the bioinspired oxidative transformation of leucosceptroid A to leucosceptroids C, K, O, and P using singlet oxygen supports the hypothesis that leucosceptroids A and B are most likely the biogenetic precursors of all other members of this natural product family

Short and Efficient Synthetic Route to Methyl α-Trioxacarcinoside B and Anomerically Activated Derivatives

A 9-step synthetic route to the complex carbohydrate methyl α-trioxacarcinoside B from 2-acetylfuran is described. Anomerically activated forms, including 1-phenylthio, 1-O-(4′-pentenyl), 1-fluoro, and 1-O-acetyl derivatives are also prepared

A Bioinspired Cyclization Sequence Enables the Asymmetric Total Synthesis of Dictyoxetane

We have developed the first synthesis of the unique oxetane containing diterpene (+)-dictyoxetane. Our retrosynthetic planning was guided by the putative biosynthesis of the unprecedented 2,7-dioxatricyclo­[4.2.1.03,8]­nonane ring system. A bioinspired 4-exo-tet, 5-exo-trig cyclization sequence enabled the construction of the synthetically challenging dioxatricyclic framework. The overall synthesis proceeds in 15 linear steps from a known and readily available trans-hydrindane fragment. In addition, we were able to realize the first dyotropic rearrangement of an epoxide–oxetane substrate

Sequential O–H/C–H Bond Insertion of Phenols Initiated by the Gold(I)-Catalyzed Cyclization of 1‑Bromo-1,5-enynes

The development of a sequential O–H/C–H bond functionalization of phenols initiated by the cationic gold­(I)-catalyzed cyclization of 1-bromo-1,5-enynes to produce (2-bromocyclopent-2-en-1-yl)­phenols is reported. This unprecedented domino transformation efficiently proceeds under mild conditions (5 mol % of (<i>t</i>-Bu)₃PAuNTf₂, CH₂Cl₂, 0–23 °C) via an intermediate aryl alkyl ether which collapses at ambient temperature to undergo a 1,2-hydride shift followed by C–H insertion of the phenol

A Bioinspired Cyclization Sequence Enables the Asymmetric Total Synthesis of Dictyoxetane

We have developed the first synthesis of the unique oxetane containing diterpene (+)-dictyoxetane. Our retrosynthetic planning was guided by the putative biosynthesis of the unprecedented 2,7-dioxatricyclo­[4.2.1.0^3,8]­nonane ring system. A bioinspired 4-<i>exo</i>-tet, 5-<i>exo</i>-trig cyclization sequence enabled the construction of the synthetically challenging dioxatricyclic framework. The overall synthesis proceeds in 15 linear steps from a known and readily available <i>trans</i>-hydrindane fragment. In addition, we were able to realize the first dyotropic rearrangement of an epoxide–oxetane substrate

Ring Expansion of 1‑Indanones to 2‑Halo-1-naphthols as an Entry Point to Gilvocarcin Natural Products

Herein, we describe a two-step ring expansion of 1-indanones to afford 2-chloro/bromo-1-naphthols (32 examples). The developed method shows broad functional group tolerance, benefits from mild reaction conditions, and enables rapid access to the tetracyclic core of gilvocarcin natural products. The orthogonally functionalized products allow for selective postmodifications as exemplified in the total synthesis of defucogilvocarcin M. For the selective oxidation of the chromene, a mild and regioselective oxidation protocol (DDQ and TBHP) was developed

Synthesis of the Tetracyclic Spiro-naphthoquinone Chartspiroton

Chartspiroton is a recently discovered naphthoquinone natural product that features a spiro-fused benzofuran lactone. We report its first synthesis via an 11-step linear sequence. The sterically hindered tetra-ortho-substituted biaryl subunit was installed by base-induced ring expansion of a readily available 1,3-indandione. This step also liberated the fully substituted naphthalene core unit at the same time. The unique spiro-fused benzofuran lactone of the natural product was constructed via late-stage oxidation of an advanced naphthoquinone

Total Syntheses of (+)-Echinopine A and B: Determination of Absolute Stereochemistry

The first total syntheses of the novel 3,5,5,7-sesquiterpenoids (+)-Echinopine A (1) and B (2) were achieved. Thereby the proposed structures were confirmed, and the absolute stereochemistry was determined. The key features are (1) the stereoselective installation of the vinyl-moiety on the concave side of the bicyclo[3.3.0]octane core via Myers’ [3,3]-sigmatropic rearrangement, (2) the finding that the substituent on the C7 position next to the ketone can be epimerized to the desired concave face under basic conditions, (3) the closure of the highly strained seven-membered ring via RCM, and (4) the unusual C2-homologation of a vinyltriflate with a ketene silyl acetal

Short, Divergent, and Enantioselective Total Synthesis of Bioactive <i>ent</i>-Pimaranes

We present the first total synthesis of eight ent-pimaranes via a short and enantioselective route (11–16 steps). Key features of the divergent synthesis are a Sharpless asymmetric dihydroxylation, a Brønsted acid catalyzed cationic bicyclization, and a mild Rh-catalyzed arene hydrogenation for rapid access to a late synthetic branching point. From there on, selective functional group manipulations enable the synthesis of ent-pimaranes bearing different modifications in the A- and C-rings