Macrocyclic Lactam Synthesis via a Ring Expansion Reaction:  Construction of the Cripowellin Skeleton

Moon, Bongjin; Han, S. F.; Yoon, Yeo-Jin; Kwon, Hyejin

doi:10.1021/ol047520+

Cited by 20 publications

(16 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Purification by column chromatography (chloroform/ methanol, 14:1) yielded the desired 5,10b-ethanophenanthridine 5a-5l . The NMR spectral data for known compounds ( 5a [54] and 5b [54]) matched those in the literature. The characterization of all new compounds is given below.…”

Section: Methodssupporting

confidence: 61%

“…More recent modifications of this method involved the reactions utilizing hypervalent iodine to achieve the desired phenolic coupling. Such efforts led to the total syntheses of maritidine [49–51], siculine [52], oxocrinine [52], epicrinine [52], powelline [53], and 14,15-dideoxycripowellin [54]. Analysis of all published total syntheses of the crinine-type alkaloids reveals that the biomimetic strategy provides the shortest route to these natural products.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells

Henry

Kidner

Reisenauer

et al. 2016

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Plants of the Amaryllidaceae family produce a large variety of alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting proliferation of cancer cells resistant to various pro-apoptotic stimuli and representing tumors with dismal prognoses refractory to current chemotherapy, such as glioma, melanoma, non-small-cell lung, esophageal, head and neck cancers, among others. Using this discovery as a starting point and taking advantage of a concise biomimetic route to the crinine skeleton, a collection of crinine analogues were synthetically prepared and evaluated against cancer cells. The compounds exhibited single-digit micromolar activities and retained this activity in a variety of drug-resistant cancer cell cultures. This investigation resulted in the discovery of new bicyclic ring systems with significant potential in the development of effective clinical cancer drugs capable of overcoming cancer chemotherapy resistance.

show abstract

Section: Methodssupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells

Henry

Kidner

Reisenauer

et al. 2016

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…Macromolecules [1][2][3][4][5] have been the targets of the synthetic efforts of investigators, largely because of their widespread applications related to their medicinal, insecticidal and/or phytotoxic properties [6][7][8][9][10][11][12][13][14]. Accordingly, we endeavored to synthesize a new series of macrocyclic systems as possible candidates for biological screening.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel aromatic macrolactones via ring closing metathesis of substituted phenylalkanoic acid allylic esters

Brown

Hoàn

2008

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

show abstract

“…1 13 (E)-But-2-enoic Acid 2-Benzoyl-3-phenyl-benzofuran-4-yl Ester 7a (Scheme 3). To a solution of 1-methoxy-3-methoxymethoxy-benzene 22 (17, 0.20 g, 1.19 mmol) in dry THF (10 mL) at 0°C was added nBuLi (0.96 mL, 1.6 mol in hexane) dropwise. After addition was completed, the mixture was stirred at same temperature for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Anti-Influenza Drug Discovery: Structure−Activity Relationship and Mechanistic Insight into Novel Angelicin Derivatives

Yeh

Coumar

Horng³

et al. 2010

J. Med. Chem.

143

View full text Add to dashboard Cite

By using a cell-based high throughput screening campaign, a novel angelicin derivative 6a was identified to inhibit influenza A (H1N1) virus induced cytopathic effect in Madin-Darby canine kidney cell culture in low micromolar range. Detailed structure-activity relationship studies of 6a revealed that the angelicin scaffold is essential for activity in pharmacophore B, while meta-substituted phenyl/2-thiophene rings are optimal in pharmacophore A and C. The optimized lead 4-methyl-9-phenyl-8-(thiophene-2-carbonyl)-furo[2,3-h]chromen-2-one (8g, IC(50) = 70 nM) showed 64-fold enhanced activity compared to the high throughput screening (HTS) hit 6a. Also, 8g was found effective in case of influenza A (H3N2) and influenza B virus strains similar to approved anti-influenza drug zanamivir (4). Preliminary mechanistic studies suggest that these compounds act as anti-influenza agents by inhibiting ribonucleoprotein (RNP) complex associated activity and have the potential to be developed further, which could form the basis for developing additional defense against influenza pandemics.

show abstract

Macrocyclic Lactam Synthesis via a Ring Expansion Reaction: Construction of the Cripowellin Skeleton

Abstract: [reaction: see text] The cripowellin ring skeleton, a macrocyclic [2.3.5]-bicyclic ketolactam, was smoothly generated via construction of a spiro(benzazepin-cyclohexane-1,3-dione) employing oxidative cyclization as a key step and a subsequent ring expansion reaction.

Cited by 20 publications

References 19 publications

5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells

5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells

Synthesis of novel aromatic macrolactones via ring closing metathesis of substituted phenylalkanoic acid allylic esters

Anti-Influenza Drug Discovery: Structure−Activity Relationship and Mechanistic Insight into Novel Angelicin Derivatives

Contact Info

Product

Resources

About