Total Synthesis of Acanthodoral Using a Rearrangement Strategy.

We present the second total synthesis of (±)-acanthodoral, a sesquiterpenoid derived from the marine nudibranch . Our approach involves a concise three-step transformation from a previously reported compound, resulting in the formation of a less strained precursor of the bicyclo[3.1.

Unified Total Syntheses of Benzenoid Cephalotane-Type Norditerpenoids: Cephanolides and Ceforalides.

Detailed herein are our synthetic studies toward the preparation of the C- and C-benzenoid cephalotane-type norditerpenoids. Guided by chemical network analysis, the core structure of this natural product family was constructed in a concise manner using an iterative cross-coupling, followed by a formal inverse-electron-demand [4 + 2] cycloaddition. Initial efforts to functionalize an alkene group in the [4 + 2] cycloadduct using a Mukaiyama hydration and a subsequent olefination led to the complete C-carbon framework.

Oxazaborolidinone-Mediated Asymmetric Bisvinylogous Mukaiyama Aldol Reaction.

A bisvinylogous Mukaiyama aldol reaction using oxazaborolidinones as a source of chirality was developed. This methodology allows the fast assembly of conjugated dienols by expanding the vinylogy principle by two additional carbons, and can be conducted using a readily available Lewis acid at reasonable reaction times. A broad range of aromatic and aliphatic aldehydes can be used providing access to complex building blocks for polyketide synthesis.

Total Synthesis of the Norditerpenoids (±)-Cephanolides A-D.

Concise syntheses of the norditerpenoids cephanolides A-D (8-14 steps from commercial material) using a common late-stage synthetic intermediate are described. The success of our approach rested on an early decision to apply chemical network analysis to identify the strategic bonds that needed to be forged, as well as the efficient construction of the carbon framework through iterative Csp-Csp cross-coupling, followed by an intramolecular inverse-demand Diels-Alder cycloaddition. Strategic late-stage oxidations facilitated access to all congeners of the benzenoid cephanolides isolated to date.

Contiguous Quaternary Carbons: A Selection of Total Syntheses.

Contiguous quaternary carbons in terpene natural products remain a major challenge in total synthesis. Synthetic strategies to overcome this challenge will be a pivotal prerequisite to the medicinal application of natural products and their analogs or derivatives. In this review, we cover syntheses of natural products that exhibit a dense assembly of quaternary carbons and whose syntheses were uncompleted until recently.