The formal oxidative addition of electron-rich transoid dienes to bromonaphthoquinones

Grunwell, John R.; Karipides, A.; Wigal, Carl T.; Heinzman, Stephen W.; Parlow, John J.; Surso, J. A.; Clayton, L.; Fleitz, Fred J.; Daffner, Martin; Stevens, Jonathan E.

doi:10.1021/jo00001a020

Cited by 89 publications

(65 citation statements)

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“…We planned to introduce the 3,4-di-O-methyl-l-rhamnopyranoside and the bromodiene side chain to aglycon 3 via a stereoselective glycosylation [7] and a Stille-type reaction, [8] respectively. We planned to assemble 5 from three readily available building blocks; aldehyde 6, ester 7, and the known silyl dienol ether 8; [10] in a convergent manner by exploiting an Abiko-Masamune anti-aldol reaction [11] and a vinylogous Mukaiyama aldol reaction. [6b,d] Notably, in our hands, acylation of the C13 tertiary alcohol was impractical by any other means.…”

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confidence: 99%

Total Synthesis, Stereochemical Reassignment, and Biological Evaluation of (−)‐Lyngbyaloside B

et al. 2014

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(-)-Lyngbyaloside B is a 14-membered macrolide glycoside isolated from the marine cyanobacterium Lyngbya sp. as a cytotoxic substance by Moore and co-workers. The first total synthesis of (-)-lyngbyaloside B and the reassignment of its stereostructure is described. The synthesis features an Abiko-Masamune aldol reaction, a vinylogous Mukaiyama aldol reaction, and a macrocyclization involving an acyl ketene intermediate for the construction of the macrocyclic backbone, which contains an acylated tertiary alcohol. The antiproliferative activity of selected compounds against a small panel of human cancer cell lines is also reported.

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confidence: 99%

Total Synthesis, Stereochemical Reassignment, and Biological Evaluation of (−)‐Lyngbyaloside B

et al. 2014

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“…Pyrone formation from different aldehydes was possible by addition of ketene acetal 7, [10] oxidation with the Dess-Martin periodinane (DMP) [11] and ring closure. [12,13] Isovaleraldyde (6) for example was converted to pyrone 8 in 75 % overall yield.…”

Section: Resultsmentioning

confidence: 99%

“…The crude product was purified by flash chromatography (P/EA 98:2) to give 25 as a colorless oil (631 mg, 0.93 mmol, 98 %) which decomposed slowly at RT. R f = 0.62 (P/EA 90: 10) (27): A solution of nBuLi in hexanes (2.5 m, 1.36 mL, 3.4 mmol) at À40 8C was added to a solution of 2-phenyl-1,3-dithiane [15a] (654 mg, 3.33 mmol) in dry THF (40 mL). The resulting orange solution was stirred for 2 h at À40 8C.…”

Section: -[1-(2-methoxyethoxymethoxy)cyclohexyl]acetaldehyde (15)mentioning

confidence: 99%

Diastereoselective Reactions at Enantiomerically Pure, Sterically Congested Cyclohexanes as an Entry to Wailupemycins A and B: Total Synthesis of (+)‐Wailupemycin B

Kirsch

Bach

2005

Chemistry A European J

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Wailupemycin A (1) and B (2) are polyketide natural products with a highly substituted cyclohexanone core. Three different routes for the syntheses of these compounds were pursued, which commenced from either (R)-(-)-carvone (ent-5) or (S)-(+)-carvone (5). In the first approach it was attempted to construct the skeleton of wailupemycin A from triol 19 (nine steps from ent-5; 19 % yield) by a sequence of diastereoselective epoxidation, nucleophilic ring opening at C-13 and carbonyl addition at C-5. The synthetic plan failed at the stage of the carbonyl addition to aldehyde 27, which had been obtained in seven steps (18 % yield) from triol 19. The second route included an epoxide ring opening at C-13 and a carbonyl addition at C-7 as key steps. It could have led to either wailupemycin A or B depending on the diastereoselectivity of the addition step. Starting from allylic alcohol 30 (six steps from ent-5; 59 % yield) the cyclohexanone 28 was obtained in five steps (54 % yield). Unfortunately, the carbonyl addition failed also in this instance. In the eventually successful third attempt the skeleton of wailupemycin B was built from cyclohexanone 43 (eight steps from 5; 53 % yield) by highly diastereoselective carbonyl addition reactions at C-7 and C-12. The phenyl group at C-14 was introduced at a late stage of the synthetic sequence. Careful protecting group manipulation finally allowed for the total synthesis of (+)-wailupemycin B. The absolute and relative configuration of the natural product was unambiguously confirmed. The total yield of wailupemycin B amounted to 6 % over 23 steps starting from (S)-(+)-carvone (5).

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“…Dioxinones have been used as masked β -ketoesters and as precursors to extended enolates. 22,23 However, their use as nucleophiles is quite uncommon, with only one example when our Prins approach was initially disclosed. 24 …”

Section: Lewis Acid Mediated Pyranone Synthesismentioning

confidence: 99%

Pyranone Natural Products as Inspirations for Catalytic Reaction Discovery and Development

McDonald

Scheidt

2015

Acc. Chem. Res.

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CONSPECTUS Natural products continue to provide a wealth of opportunities in the areas of chemical and therapeutic development. These structures are effective measuring sticks for the current state of chemical synthesis as a field and constantly inspire new approaches and strategies. Tetrahydropryans and tetrahydropyran-4-ones are found in numerous bioactive marine natural products and medicinal compounds. Our interest in exploring the therapeutic potential of natural products containing these motifs provided the impetus to explore new methods to access highly functionalized, chiral pyran molecules in the most direct and rapid fashion possible. This goal led to exploration and development of a Lewis acid-mediated Prins reaction between a chiral β-hydroxy-dioxinone and aldehyde to produce a pyran–dioxinone fused product that can be processed in a single pot operation to the desired tetrahydropyran-4-ones in excellent yield and stereoselectivity. Although the Prins reaction is a commonly employed approach toward pyrans, this method uniquely provides a 3-carboxy-trisubstituted pyran and utilizes dioxinones in a manner that was underexplored at the time. The 3-carboxy substituent served as a key synthetic handhold when this method was applied to the synthesis of highly functionalized pyrans within the macrocyclic natural products neopeltolide, okilactiomycin, and exiguolide. When employed in challenging macrocyclizations, this tetrahydropyranone forming reaction proved highly stereoselective and robust. Another major thrust in our lab has been the synthesis of benzopyranone natural products, specifically flavonoids, because this broad and diverse family of compounds possesses an equally broad range of biological and medicinal applications. With the goal of developing a broad platform toward the synthesis of enantioenriched flavonoid analogs and natural products, a biomimetic, asymmetric catalytic approach toward the synthesis of 2-aryl benzopyranones was developed. A bifunctional hydrogen bonding/ Brønstead base catalyst was ultimately found to enable this transformation in analogous manner to the biosynthesis via the enzyme chalcone isomerase. Employing thiourea catalysts derived from the pseudoenantiomeric quinine and quinidine, alkylidene β-ketoesters can be isomerized to 3-carboxy flavanones and decarboxylated in a single pot operation to stereodivergently provide highly enantioenriched flavanones in excellent yield. This method was applied to the synthesis of the abyssinone family of natural products, as well as the rotenoid, deguelin. An analogous method to isomerize chalcones was developed and applied to the synthesis of isosilybin A. In both of these related endeavors, the need for novel enabling methodologies toward the efficient creation of targeted molecular complexity drove the discovery, development and deployment of these stereoselective catalytic transformations.

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The formal oxidative addition of electron-rich transoid dienes to bromonaphthoquinones

Cited by 89 publications

References 0 publications

Total Synthesis, Stereochemical Reassignment, and Biological Evaluation of (−)‐Lyngbyaloside B

Total Synthesis, Stereochemical Reassignment, and Biological Evaluation of (−)‐Lyngbyaloside B

Diastereoselective Reactions at Enantiomerically Pure, Sterically Congested Cyclohexanes as an Entry to Wailupemycins A and B: Total Synthesis of (+)‐Wailupemycin B

Pyranone Natural Products as Inspirations for Catalytic Reaction Discovery and Development

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