We report the first total synthesis of (−)-N-methylwelwitindolinone C isothiocyanate. Our route features a number of key transformations, including an indolyne cyclization to assemble the ...4.3.1-bicyclic scaffold, as well as a late-stage intramolecular nitrene insertion to functionalize the C11 bridgehead carbon en route to the natural product.
We report the total synthesis of (−)-N-methylwelwitindolinone C isonitrile, in addition to the total syntheses of the 3-hydroxylated welwitindolinones. Our routes to these elusive natural products ...feature the strategic use of a deuterium kinetic isotope effect to improve the efficiency of a late-stage nitrene insertion reaction. We also provide a computational prediction for the stereochemical configuration at C3 of the hydroxylated welwitindolinones, which was confirmed by experimental studies.
The total synthesis of N‐methylwelwitindolinone D isonitrile (1) has been achieved in 17 steps from a readily available carvone derivative. The route features a double C–H functionalization event ...involving a keto oxindole substrate to introduce the tetrahydrofuran ring of the natural product.
The welwitindolinones with bicyclo4.3.1 cores are a class of natural products that have attracted tremendous interest from the synthetic community because of their fascinating structures and ...promising biological profiles. More than 15 research groups worldwide have reported progress toward these elusive natural products. This Minireview describes contemporary studies aimed at the total synthesis of these challenging targets, in addition to the two recently completed syntheses of welwitindolinones with bicyclo4.3.1 cores reported by Rawal and Garg in 2011. Both of the completed efforts rely on C4C11 bond constructions to access the congested bicyclic framework of these elusive natural products.
17 years in the making: The welwitindolinones with bicyclo4.3.1 cores are a class of natural products that have attracted tremendous interest from the synthetic community. Contemporary studies aimed at the total synthesis of these challenging targets are described, including two recently completed syntheses (see one example).
An overview of Parkinson’s disease (PD) prevalence, diagnosis, and currently available treatment options is provided. A comprehensive list of different classes of marketed pharmaceutical drug ...products and the syntheses of various drug substances are summarized based on published literature.
Foslevodopa (FLD, levodopa 4′-monophosphate, 3) and foscarbidopa (FCD, carbidopa 4′-monophosphate, 4) were identified as water-soluble prodrugs of levodopa (LD, 1) and carbidopa (CD, 2), ...respectively, which are useful for the treatment of Parkinson’s disease. Herein, we describe asymmetric syntheses of FLD (3) and FCD (4) drug substances and their manufacture at pilot scale. The synthesis of FLD (3) employs a Horner–Wadsworth–Emmons olefination reaction followed by enantioselective hydrogenation of the double bond as key steps to introduce the α-amino acid moiety with the desired stereochemistry. The synthesis of FCD (4) features a Mizoroki–Heck reaction followed by enantioselective hydrazination to install the quaternary chiral center bearing a hydrazine moiety.
Synthetic Studies Inspired by Vinigrol Huters, Alexander D.; Garg, Neil K.
Chemistry : a European journal,
August 2, 2010, Letnik:
16, Številka:
29
Journal Article
Recenzirano
Vinigrol, a diterpene natural product, has been a fascinating target for total synthesis for over two decades. This minireview describes recent synthetic studies that have ultimately allowed access ...to the coveted vinigrol scaffold. Barriault’s synthesis of the vinigrol core is described, in addition to the elegant strategies disclosed by Njarđarson and Hanna. The first total synthesis of vinigrol, reported by Baran in 2009, is also highlighted. This review showcases the fundamental role that natural products play in spawning innovations in synthetic chemistry.
Vinigrol, a diterpene natural product, has been a fascinating target for total synthesis for over two decades. Recent synthetic studies that have ultimately allowed access to the coveted vinigrol scaffold, including the approaches reported by Barriault, Njarđarson, and Hanna, as well as the first total synthesis of vinigrol, reported by Baran in 2009, are described.
A concise synthesis of the N-methylwelwitindolinone C isothiocyanate scaffold is disclosed. The approach relies on an indolyne cyclization to construct the 4.3.1-bicyclic ring system present in the ...natural product. Subsequent oxidation of the indole core occurs with excellent diastereoselectivity to afford oxindole 2, the structure of which was confirmed by X-ray crystallographic analysis.
Why Do Some Fischer Indolizations Fail? Çelebi-Ölçüm, Nihan; Boal, Ben W; Huters, Alexander D ...
Journal of the American Chemical Society,
04/2011, Letnik:
133, Številka:
15
Journal Article
Recenzirano
Odprti dostop
The mechanisms of the Fischer indole synthesis and competing cleavage pathways were explored with SCS-MP2/6-31G(d) and aqueous solvation calculations. Electron-donating substituents divert the ...reaction pathway to heterolytic N−N bond cleavage and preclude the acid-promoted 3,3-sigmatropic rearrangement.
The total synthesis of N-methylwelwitindolinoneD isonitrile (1) has been achieved in 17 steps from a readily available carvone derivative. The route features a double C-H functionalization event ...involving a keto oxindole substrate to introduce the tetrahydrofuran ring of the natural product.
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