Abstract:Das 1,4‐ Cyclohexadien (I) liefert über eine in‐situ‐Isomerisierung zu (II) mit α‐Chloracrylnitril (III) die isomeren Addukte (IV), die zum Keton (Va) hydrolysiert werden.
“…Hampered by what was then undesired reactivity, we were eager to productively utilize this rearrangement toward the gibberellin family. We are not the first to approach the gibberellin C/D ring junction via a [2.2.2]- to [3.2.1]-bicycle rearrangement as Mori, Monti, and Yamada reported their efforts in the 1970s utilizing acid–based rearrangement approaches . However, these prior rearrangement approaches were unable to successfully access gibberellin natural products.…”
Synthetic studies toward the gibberellin family of natural products are reported. An oxidative dearomatization/Diels-Alder cascade assembles the carbon skeleton as a [2.2.2]-bicycle, which is then transformed to the [3.2.1]-bicyclic gibberellin core via a novel Lewis acid catalyzed rearrangement. Strategic synthetic handles allow for late-stage modification of the gibberellin skeleton and provides efficient access to this important family of natural compounds.
“…Hampered by what was then undesired reactivity, we were eager to productively utilize this rearrangement toward the gibberellin family. We are not the first to approach the gibberellin C/D ring junction via a [2.2.2]- to [3.2.1]-bicycle rearrangement as Mori, Monti, and Yamada reported their efforts in the 1970s utilizing acid–based rearrangement approaches . However, these prior rearrangement approaches were unable to successfully access gibberellin natural products.…”
Synthetic studies toward the gibberellin family of natural products are reported. An oxidative dearomatization/Diels-Alder cascade assembles the carbon skeleton as a [2.2.2]-bicycle, which is then transformed to the [3.2.1]-bicyclic gibberellin core via a novel Lewis acid catalyzed rearrangement. Strategic synthetic handles allow for late-stage modification of the gibberellin skeleton and provides efficient access to this important family of natural compounds.
“…To generate one- and multidimensional libraries containing a cedrane core, a scaffold with three orthogonally reactive chemical handles was synthesized on a 5 g scale (Scheme ). − Briefly, the methylation of 7 with iodomethane was promoted by potassium carbonate in refluxing acetone to give 8 in 85% yield . Then, Birch reduction of 8 yielded 9 (70%).…”
Section: Resultsmentioning
confidence: 99%
“…Then, Birch reduction of 8 yielded 9 (70%). Cycloaddition of acrylonitrile and the conjugated diene 10 , generated in situ from 9 , gave a mixture of nitriles 11a and b . Deprotonation of 11 with lithium diisopropylamide followed by treatment with oxygen, and subsequent reduction with sodium sulfite gave the ketone 12 in 72% yield.…”
Section: Resultsmentioning
confidence: 99%
“…Cycloaddition of acrylonitrile and the conjugated diene 10, generated in situ from 9, gave a mixture of nitriles 11a and b. 39 Deprotonation of 11 with lithium diisopropylamide followed by treatment with oxygen, and subsequent reduction with sodium sulfite gave the ketone 12 in 72% yield. Ketone 12 was then treated with 2-(2-bromoethyl)-1,3-dioxane and magnesium turnings in THF to obtain a readily separable mixture of endo (13a) and exo alcohols (13b) in 62:38 ratio in good yield (75%).…”
A chemoinformatic method was developed to extract nonflat scaffolds embedded in natural products within the Dictionary of Natural Products (DNP). The cedrane scaffold was then chosen as an example of a nonflat scaffold that directs substituents in three-dimensional (3D) space. A cedrane scaffold that has three orthogonal handles to allow generation of 1D, 2D, and 3D libraries was synthesized on a large scale. These libraries would cover more than 50% of the natural diversity of natural products with an embedded cedrane scaffold. Synthesis of three focused natural product-like libraries based on the 3D cedrane scaffold was achieved. A phenotypic assay was used to test the biological profile of synthesized compounds against normal and Parkinson's patient-derived cells. The cytological profiles of the synthesized analogues based on the cedrane scaffold revealed that this 3D scaffold, prevalidated by nature, can interact with biological systems as it displayed various effects against normal and Parkinson's patient-derived cell lines.
“…Construction of the tricyclo[5.3.1.0 1,5 ]undecane system, which constitutes the basic carbon framework of natural products such as cedranes, has been a continuous challenge to synthetic organic chemists and has led to the development of diverse synthetic strategies . Thus, we believed pinacol rearrangement of simple Diels−Alder derived bicyclo[2.2.2]octene system 2a , followed by an ene reaction, would lead to the efficient formation of highly fuctionalized tricyclo[5.3.1.0 1,5 ]undecane system 1a via the intermediacy of bicyclo[3.2.1]octene derivative 3 as illustrated in Scheme . 1 …”
Histrionicotoxin derivatives have long been attractive targets for synthetic chemists as a result of their useful neurophysical properties, low natural abundance, and the unique structural features of the azaspiro[5.5]undecane ring system. Utilizing our tandem pinacol rearrangement-ene strategy and regiospecific Baeyer-Villiger oxidation as key steps, we have successfully synthesized an advanced synthetic intermediate, spiro[5.4]decane 4, which has previously been converted to (+/-)-perhydrohistrionicotoxin (5b). Pinacol rearrangement of simple Diels-Alder derived bicyclo[2.2.2]octene system 2a, followed by an ene reaction, led to the efficient formation of the highly fuctionalized tricyclo[5.3.1.0(1,5)]undecane system 1a. This tricyclic system 1a was selectively transformed into spiro[5. 4]decane system 4 via a regiospecific Baeyer-Villiger oxidation reaction. We also report the results of systematic studies of Baeyer-Villiger oxidation reactions of tricyclo[5.3.1.0(1, 5)]undecanone systems to elucidate the origin of the regioselectivity of this process.
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