Synthesis of saframycins. II. Preparations and reactions of N-methyl-2,5-piperazinediones.

Kubo, Akinori; Saito, Naoki; Yamato, H.; Yamauchi, Reiko; Hiruma, Kazumi; Inoue, Satoshi

doi:10.1248/cpb.36.2607

Cited by 24 publications

(12 citation statements)

References 2 publications

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“…Related synthetic studies were performed by A. Kubo et al on the synthesis of saframycin A [20], in the transformation of (±)-saframycin B to (±)-saframycin C and D [21], and in the transformation of (-)-saframycin A to (-)saframycin Mx [22], using SeO 2 in different reaction solvents (Scheme 2).…”

Section: Synthetic Routes To the Saframycinsmentioning

confidence: 99%

Advances in the Chemistry and Pharmacology of Ecteinascidins, A Promising New Class of Anticancer Agents

Manzanares¹,

Cuevas²,

Garcı́a-Nieto³

et al. 2001

CMCACA

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Ecteinascidins are marine natural products consisting of two or three linked tetrahydroisoquinoline subunits and an active carbinolamine functional group. Their potent antiproliferative activity against a variety of tumor cells has made them attractive candidates for development as anticancer agents. The lead compound, ecteinascidin 743 (ET 743), is currently in phase II clinical trials but the low amounts present in its natural source, the tunicate Ecteinascidia turbinata, made it necessary to develop efficient synthetic procedures. Recent improvements on the original synthesis are reviewed as well as new strategies starting from readily available cyanosafracin B. ET 743 is known to bind to the minor groove of DNA giving rise to a covalent adduct with the exocyclic amino group at position 2 of a guanine in a fashion similar to saframycin antibiotics. Some of the resulting complexes have been studied by a variety of biochemical and spectroscopic methods and also by computer simulations. The rules for sequence specificity have been well established (preferred targets are RGC and YGG, where R and Y stand for purine and pyrimidine, respectively), and it has been shown that binding of ET 743 to DNA is accompanied by minor groove widening and DNA bending towards the major groove. Although the precise target for antitumor action remains to be unambiguously defined, a role in affecting the transcriptional regulation of some inducible genes is rapidly emerging.

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Section: Synthetic Routes To the Saframycinsmentioning

confidence: 99%

Advances in the Chemistry and Pharmacology of Ecteinascidins, A Promising New Class of Anticancer Agents

Manzanares¹,

Cuevas²,

Garcı́a-Nieto³

et al. 2001

CMCACA

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“…We have reported the preparation of alcohol 6a having trans configuration at C-6 to C-11a, which involved the stereoselective Pictet-Spengler type cyclization of N-methyl-3-arylmethylpiperazine-2,5-dione 34) with ethyl diethoxyacetate, followed by chemoselective transformation. 35) We first studied the conversion of trans isomer 6a into cis-alcohol 6b (Chart 1).…”

Section: Resultsmentioning

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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“…The stereospecific intramolecular Pictet–Spengler cyclization is one of the key steps for the construction of the pentacyclic skeleton of the bistetrahydroisoquinoline alkaloids. Organic acids such as HCOOH, MeSO 3 H, CF 3 SO 3 H, and CF 3 COOH have been used to realize the cyclization [6–23]. Previous research in our group mainly focused on the study of new approaches to construct the pentacyclic skeleton and the discovery of simplified derivatives of the bistetrahydroisoquinoline alkaloids [24].…”

Section: Introductionmentioning

confidence: 99%

Scherfließen und Wandgleiten von Massen für den Pulverspritzguss

Hage

Aichele

2015

Chemie Ingenieur Technik

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Der vorliegende Beitrag beschreibt die Koppelung von Modellen für Scherfließen und Wandgleiten über die Wandschubspannung. Der Ansatz beinhaltet die Sonderfälle einer Coulombschen Wandreibung nach Uhland und einer über die Kapillarlänge konstanten Wandgleitgeschwindigkeit nach Mooney. Als Beispiel wird das Fließmodell für strukturviskose Fluide nach Ostwald und de Waele mit einer Wandschubspannung verknüpft, die im Gleitbereich von der Potenz des Druckes abhängt. Die untersuchten Massen für den Metallpulverspritzguss verhielten sich rheologisch entsprechend dem beschriebenen Modell.

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Synthesis of saframycins. II. Preparations and reactions of N-methyl-2,5-piperazinediones.

Cited by 24 publications

References 2 publications

Advances in the Chemistry and Pharmacology of Ecteinascidins, A Promising New Class of Anticancer Agents

Advances in the Chemistry and Pharmacology of Ecteinascidins, A Promising New Class of Anticancer Agents

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

Scherfließen und Wandgleiten von Massen für den Pulverspritzguss

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