Total Synthesis of the Marine Natural Product (−)‐Cribrostatin 4 (Renieramycin H)

Chen, Xiaochuan; Zhu, Jieping

doi:10.1002/anie.200700539

Cited by 50 publications

(28 citation statements)

References 46 publications

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“…In their synthesis of renieramycin H, the Zhu group has interestingly reported control of Pictet-Spengler regioselectivity in a related system by variation of acid concentration xxiii. It was found in that case that lowering the concentration of methanesulfonic acid to 0.1% in CH 2 Cl 2 could invert the ortho:para selectivity from 3.4:1 to 2:3.…”

Section: Resultsmentioning

confidence: 99%

Synthetic Studies on Et-743. Assembly of the Pentacyclic Core and a Formal Total Synthesis

Fishlock

Williams

2008

J. Org. Chem.

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A formal total synthesis of the potent anticancer agent Et-743 is described. The tetrahydroisoquinoline core is stereoselectively constructed using a novel radical cyclization of a glyoxalimine. Further elaboration of this core rapidly accessed the pentacyclic core of Et-743, but a mixture of regiosisomers was obtained in the key Pictet-Spengler ring closure. A known advanced intermediate in the synthesis of Et-743 was intercepted, constituting a formal synthesis of the molecule.

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Section: Resultsmentioning

confidence: 99%

Synthetic Studies on Et-743. Assembly of the Pentacyclic Core and a Formal Total Synthesis

Fishlock

Williams

2008

J. Org. Chem.

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“…Keywords: alkaloids · alkylation · click chemistry · organocatalysis · sesamol tries 2-4), quinine (2 a) was found to yield 7 a in a good 75 % yield with enhanced 30 % ee (Table 1, entry 3). Encouraged by this result, we studied the catalytic ability of modified Cinchona alkaloids on the same reaction (Table 1, entries [5][6][7][8][9][10][11][12][13][14]. Cupreine (2 c) provided 7 a in good yield (77 %), but with low enantioselectivity (21 % ee; Table 1, entry 6), whereas its pseudoenantiomeric partner cupreidine (1 c) offered moderate enantioselectivity (50 % ee; Table 1, entry 5).…”

Section: Resultsmentioning

confidence: 99%

“…[10] As an electron-rich phenol, sesamol and its derivatives are good nucleophiles for Friedel-Crafts reactions to construct complex natural products. [11] Jurd et al reported the Mannichtype Friedel-Crafts aminoalkylation of sesamol and the application of the resulting Mannich bases in the synthesis of antitumor agents. [12] Frackenpohl et al also reported the same reaction and its application to the synthesis of insecticidal heterolignans.…”

Section: Introductionmentioning

confidence: 99%

Organocatalytic Asymmetric Friedel–Crafts Reaction of Sesamol with Isatins: Access to Biologically Relevant 3‐Aryl‐3‐hydroxy‐2‐oxindoles

Kumar

Kaur

Chauhan

et al. 2014

Chemistry An Asian Journal

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The Friedel-Crafts reaction of electron-rich phenols with isatins was developed by employing bifunctional thiourea-tertiary amine organocatalysts. Cinchona alkaloid derived thiourea epiCDT-3 a efficiently catalyzed the Friedel-Crafts-type addition of phenols to isatin derivatives to provide 3-aryl-3-hydroxy-2-oxindoles 7 and 9 in good yield (80-95 %) with good enantiomeric excess (83-94 %). Friedel-Crafts adduct 7 t was subjected to a copper(I)-catalyzed azide-alkyne cycloaddition to obtain biologically important 3-aryl-3-hydroxy-2-oxindole 11 in good enantiomeric excess and having a 1,2,3-triazole moiety.

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“…Renieramycin G and cribrostatin 4 are tetrahydroisoquinolines possessing a C-21 lactam carbonyl group; however, they exhibit low cytotoxicity and are less active than their respective C-21 cyano or carbinolamine containing relatives. To date, five total syntheses of renieramycin G [15][16][17][18][19][20][21] and four total syntheses of cribrostatin 4 [22][23][24][25] have been published. Several studies on the SAR of renieramycins, including renieramycin G and cribrostatin 4, were conducted, 8,[26][27][28][29][30] but the cytotoxicity profiles of these compounds were not addressed.…”

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confidence: 99%

Preparation of Tricyclic Lactam Model Compounds of Renieramycin and Saframycin Anticancer Natural Products from Common Intermediate

Nakai

Yokoya

Saito

2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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Tricyclic lactam model compounds of the left half (ABC ring) of renieramycin and saframycin anticancer natural products were prepared from common intermediate 6a. Readily available alcohol 6a was converted into enamide 8, and this was followed by transformation into 6b through a hydrobromination reaction in a stereoselective manner. Some diastereomers at C-6 to C-11a of the tricyclic lactam model compounds having several functional groups at C-6 were prepared from 6a or 6b in good yields. We presented also an unexpected reductive acetylation of the p-quinone to produce the corresponding 3,4-dehydro derivative.Key words renieramycin; saframycin; tetrahydroisoquinoline; hydrobromination; preparation; reductive acylation Tetrahydroisoquinoline natural products, including renieramycins, saframycins, ecteinascidins, naphthyridinomycins, and quinocarcins, have persistently attracted considerable interest for more than 30 years due to their novel structures and meager availability in nature, as well as their potent antitumor activity 1,2) ( Fig. 1). Ecteinascidin 743, in particular, has received considerable attention for its strong in vivo activity.3)It is currently marketed in over fifty countries for the treatment of soft-tissue sarcoma and phase II/III clinical trials for the treatment of other cancers are ongoing. 4,5) In the course of our research of new metabolites from marine animals, we isolated renieramycin M in gram scale from the Thai blue sponge Xestospongia sp. by pretreatment with potassium cyanide.6,7) Structure-activity relationship (SAR) investigations of a variety of derivatives of renieramycin M 8-10) yielded several pieces of evidence pointing to the fact that virtually all biologically active members of this family of natural products, such as 1, possess a carbinolamine or cyano function at C-21, which permits the formation of potent electrophilic iminium ion species 2, a compound that has been implicated in the formation of covalent bonds with DNA and possibly other bio macromolecules (Fig. 2). We are also very interested in the biological activities of renieramycin G 11) and cribrostatin 4 (=renieramycin H [12][13][14] ) because both compounds show antiproliferative activity. Renieramycin G and cribrostatin 4 are tetrahydroisoquinolines possessing a C-21 lactam carbonyl group; however, they exhibit low cytotoxicity and are less active than their respective C-21 cyano or carbinolamine containing relatives. To date, five total syntheses of renieramycin G [15][16][17][18][19][20][21] and four total syntheses of cribrostatin 4 22-25) have been published. Several studies on the SAR of renieramycins, including renieramycin G and cribrostatin 4, were conducted, 8,[26][27][28][29][30] but the cytotoxicity profiles of these compounds were not addressed.Among a handful of studies of simple models containing a lactam ring, such as 3, Ong and coworkers reported that pentacyclic scaffold 4 showed low cytotoxicity.31,32) Avendaño and coworkers discovered that pyrazino[1.2-b] isoquinoline-4-one derivative 5 in...

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Total Synthesis of the Marine Natural Product (−)‐Cribrostatin 4 (Renieramycin H)

Cited by 50 publications

References 46 publications

Synthetic Studies on Et-743. Assembly of the Pentacyclic Core and a Formal Total Synthesis

Synthetic Studies on Et-743. Assembly of the Pentacyclic Core and a Formal Total Synthesis

Organocatalytic Asymmetric Friedel–Crafts Reaction of Sesamol with Isatins: Access to Biologically Relevant 3‐Aryl‐3‐hydroxy‐2‐oxindoles

Preparation of Tricyclic Lactam Model Compounds of Renieramycin and Saframycin Anticancer Natural Products from Common Intermediate

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