Total Synthesis of Lennoxamine and Chilenine via Ring-Expansion of Iso- indoloisoquinoline to Isoindolobenz- azepine

Carbohydrate-derived cyclopropanes combine both the stereochemical wealth of carbohydrates and the reactivity of cyclopropanes. A diverse variety of reaction modes for these cyclopropyl carbohydrates can be harnessed for the synthesis of natural products and other targets. The natural products (−)-TAN-2483A and (−)-TAN-2483B are fungal secondary metabolites displaying a variety of bioactivities such as inhibition of c-src kinase action and parathyroid hormone-induced bone resorption. This thesis described several synthetic approaches to the natural product (−)-TAN-2483B and analogues of (−)-TAN-2483B employing cyclopropane ring expansion. The synthetic route to (−)-TAN-2483B began with the readily available substrate D-mannose. The pyran ring unsaturation of the natural product was established by a cyclopropanation-ring expansion sequence. A synthetic strategy via dichlorocyclopropane-based intermediates is described in chapter 2. This being unsuccessful, an alternative approach via 2-fomyl-glycal was developed in chapter 3. The chapter 2 and 3 provided a solid background for the achievement of the analogues synthesis illustrated in chapter 4 via dibromocyclopropane. Lewis acid-mediated alkynylation followed by Pdcatalysed carbonylative lactonisation was successfully utilised in the revelation of the furo[3,4-b]pyran ring skeleton. This route afforded analogues of TAN-2483B; the Z-and E-unsaturated ethyl esters 140 and 141 and hydroxy(−)-TAN-2483B 145. The total synthesis of (−)-TAN-2483B was not achieved due to unforeseen obstacles encountered in the deoxygenation of the side arm of 335 (Chapter 4) into the E-propenyl side arm of (−)-TAN-2483B.

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A Concise Total Synthesis of (±)-Vibralactone

10.26434/chemrxiv.7245167 ◽

2018 ◽

Author(s):

Sepand Nistanaki ◽

Luke A. Boralsky ◽

Roy D. Pan ◽

Hosea Nelson

Keyword(s):

Total Synthesis ◽

Natural Product ◽

Early Stage ◽

Ring Expansion ◽

Biologically Active ◽

Valence Isomerization ◽

Reduction Strategy ◽

Quaternary Stereocenter

Disclosed is a four-step synthesis of (±)-vibralactone, a biologically active terpenoid natural product. A key photochemical valence isomerization of 3-prenyl-pyran-2-one forges both the all-carbon quaternary stereocenter and the β-lactone at an early stage. Cyclopropanation of the resulting bicyclic β-lactone furnishes a strained housane structure that is converted to the natural product through a sequential ring expansion and reduction strategy. Our concise and modular route to the natural product provides the shortest total synthesis of (±)-vibralactone reported to date.

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Oxidative Ring Expansion of Cyclobutanols: Access to Functionalized 1,2-Dioxanes

10.26434/chemrxiv.13386917.v1 ◽

2020 ◽

Author(s):

María Martín López Martín López ◽

Nicolas Jamey ◽

Alexis Pinet ◽

Bruno Figadère ◽

Ferrié Laurent

Keyword(s):

Total Synthesis ◽

Lewis Acid ◽

Ring Expansion ◽

Alkoxy Radical ◽

Tertiary Alcohols ◽

Radical Traps ◽

Oxidative Ring Expansion

Cyclobutanols undergo an oxidative ring expansion into 1,2-dioxanols by using Co(acac)2 and triplet oxygen (3O2) as radical promoters. The formation of an alkoxy radical drives to the regioselective break of the strained ring with stabilization of a new radical on the most substituted side. The radical traps then oxygen to form 1,2-dioxanols. The reaction is particularly effective on secondary cyclobutanols but can work also on tertiary alcohols. Further acetylation generates peroxycarbenium species under catalytic Lewis acid conditions, which react with neutral nucleophiles. Many original 1,2-dioxanes, which would be difficult to prepare by another method, were then obtained with a preferred 3,6-cis-configuration. This method provides an interesting access to the total synthesis of many natural endoperoxides.

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