Recent progress in the chemistry of monoterpenoid indole alkaloids derived from secologanin

Leonard, John

doi:10.1039/a707500f

Cited by 128 publications

(46 citation statements)

References 91 publications

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“…However, lactam 9 was isolated in 60% yield when Ag 3 PO 4 was added to the reaction (entry 4). The combination of Pd 2 (dba) 3 and BINAP was also able to promote the cyclization in the presence of Ag 3 PO 4 (entry 5). Nolan's NHC catalyst was not effective (entry 6).…”

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“…Motivated by their bioactivities and attractive polycyclic structures, enormous synthetic studies on this class of compounds have been carried out. [3][4][5][6][7][8][9] Since the bond formation between the indole and the terpenoid moiety had been well resolved, much effort has been made to enhance the stereoselective construction of the quaternary carbon. Among these studies, strategies based on chiral auxiliary are dominant, and catalytic enantioselective method remains as a challenging task.…”

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Toward General Access to the <i>Aspidosperma</i>-Type Terpenoid Indole Alkaloids: Synthesis of the Key 3,3-Disubstituted Piperidones through Enantioselective Intramolecular Heck-Type Reaction of Chloroformamides

Yasui

Takeda

Takemoto

2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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An enantioselective intramolecular Heck-type reaction of chloroformamides has been developed for the synthesis of 3,3-disubstituted piperidones. The desired piperidone was formed in the presence of a palladium catalyst, an optically active phosphoramidite ligand, K 3 PO 4 and Ag 3 PO 4 . The obtained piperidone was converted to epieburnamonine.Key words enantioselective reaction; total synthesis; terpenoid indole alkaloid Chem. Pharm. Bull. 56(11) 1567-1574 (2008) © 2008 Pharmaceutical Society of Japan * To whom correspondence should be addressed. e-mail: takemoto@pharm.kyoto-u.ac.jp under normal conditions (entries 1-3). However, lactam 9 was isolated in 60% yield when Ag 3 PO 4 was added to the reaction (entry 4). The combination of Pd 2 (dba) 3 and BINAP was also able to promote the cyclization in the presence of Ag 3 PO 4 (entry 5). Nolan's NHC catalyst was not effective (entry 6).With these results in hand, syntheses of each cis-trans isomer of alkenyl chloroformamide 2 were performed. Alkene (E)-4 was synthesized through hydroalumination as a key step (Fig. 5). 4-Pentyn-1-ol (10) was transformed into alcohol 11 through oxidation, acetalization, and hydroxymethylation using benzotriazolylmethanol (BtCH 2 OH). 22) Alcohol 11 was then subjected to the hydroalumination-iodination sequence 23,24) to give (Z)-iodo alkene 12, whose configuration was confirmed by NOE experiment. Ethylation by Suzuki coupling, followed by benzylation gave the desired alkene (E)-4.Change of the starting material afforded the alternative stereoisomer (Fig. 6). (Z)-Iodoalkene 14 was synthesized from 2-pentyn-1-ol (13) through hydroalumination and iodination. Since benzylation of the hydroxy group under either basic or acidic conditions competed with decomposition of the starting material, protection by THP group was carried out. The resultant THP ether 15 underwent Negishi coupling with 3,3-(dimethoxy)propylzinc chloride 16. 25) Selective hydrolysis of the THP ether and benzylation afforded the desired alkene (Z)-4.Alkenyl acetals (E)-4 and (Z)-4 were coupled with tryptamine 3 26) through hydrolysis and reductive amination to give amines (E)-17 and (Z)-17, respectively (Fig. 7). These compounds were converted to the corresponding chloroformamides (E)-2 and (Z)-2 by treating with triphosgene and Et 3 N.Before the enantioselective Heck-type reaction, a racemic reaction was attempted to find out a suitable palladium source ( Table 2). The cyclized product 1 was isolated after hydrolysis of the resultant enol ether. At the early stage, poor reproducibility was a serious problem. After several attempts, it was found that the activity of the catalyst is highly associated with the conditions used to mix palladium sources and ligands prior to the addition of chloroformamide 2. When [Pd(h 3 -C 3 H 5 )Cl] 2 was premixed with (p-tol) 3 P at 30°C for 30 min, the disappearance of 2 was slow and the yield was 30% after 24 h (entry 1). In contrast, the starting material disappeared in 3 h and yield reached 49% when premixing was performed at 40°C...

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Toward General Access to the <i>Aspidosperma</i>-Type Terpenoid Indole Alkaloids: Synthesis of the Key 3,3-Disubstituted Piperidones through Enantioselective Intramolecular Heck-Type Reaction of Chloroformamides

Yasui

Takeda

Takemoto

2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The neutral losses of H 2 O, C 2 H 5 N, CH 2 O, C 2 H 4 O, CH 3 OH, HCOOCH 3 , and C 4 H 6 molecules and CH 3 radical are the main CID-fragmentation patterns for compound 2 (Scheme 2). The losses of CH 3 OH and HCOOCH 3 indicate the presence of the methyl formate group in compound 2. The product ion at m/z 297 is formed by sequential losses of CH 2 O and C 2 H 4 O from the precursor ion at m/z 371 and produces the base peak at m/z 265 by losses of CH 3 OH.…”

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“…These product ions are formed by loss of a CH 3 radical from the product ions at m/z 234, 232, and 220. The product ions at m/z 168, 144, and 130 in the low-mass range are the characteristic ions of the indole part.…”

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Analysis of Monoterpenoid Indole Alkaloids Using Electrospray Ionization Tandem Mass Spectrometry

Fang

et al. 2015

Chem Nat Compd

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[6,7] properties. Well-known examples, such as vinblastine and vincristine, have been used for cancer chemotherapy [2,3]. Structural characterization is key for the study of their bioactivities. Therefore, reliable, fast, and low-cost analysis methods for this class of compounds are highly desirable. Mass spectrometry (MS), especially tandem mass spectrometry (MS/MS), is an important physicochemical method for the identification of alkaloids such as vinca alkaloids [8], plumeran indole alkaloids [9], epipolythiodioxopiperazines [10, 11], communesins [12], and uleine alkaloids [13]. In our laboratory, three monoterpenoid indole alkaloids with unique skeletons, that is echitaminic acid, N b -demethylechitamine, and N-methyl aspidodasycarpine, were isolated from the trunk barks of Winchia calophylla [14][15][16][17]. To our knowledge, these indole alkaloids have not been studied in detail by electrospray ionization (ESI)-MS/MS. Herein, the three compounds were studied with collision-induced dissociation (CID)-MS/MS using an ESI quadrupole time-of-flight (QTOF) MS/MS hybrid instrument in positive-ion mode. The aim of the study was to obtain sufficient information on the structure of these compounds, such as their degradation products, metabolites, and biosynthesis intermediates.

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Alkaloid Biosynthesis

O’Connor

2008

Wiley Encyclopedia of Chemical Biology

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How nature synthesizes complex secondary metabolites, or natural products, can be studied only by working within the disciplines of both chemistry and biology. Alkaloids are a complex group of natural products with diverse mechanisms of biosynthesis. This article highlights the biosynthesis of four major classes of plant‐derived alkaloids. Only plant alkaloids for which significant genetic information has been obtained were chosen for review. Isoquinoline alkaloid, terpenoid indole alkaloid, tropane alkaloid, and purine alkaloid biosynthesis are described here. The article is intended to provide an overview of the basic mechanism of biosynthesis for selected members of each pathway. Manipulation of these pathways by metabolic engineering is highlighted also.

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Recent progress in the chemistry of monoterpenoid indole alkaloids derived from secologanin

Cited by 128 publications

References 91 publications

Toward General Access to the <i>Aspidosperma</i>-Type Terpenoid Indole Alkaloids: Synthesis of the Key 3,3-Disubstituted Piperidones through Enantioselective Intramolecular Heck-Type Reaction of Chloroformamides

Toward General Access to the <i>Aspidosperma</i>-Type Terpenoid Indole Alkaloids: Synthesis of the Key 3,3-Disubstituted Piperidones through Enantioselective Intramolecular Heck-Type Reaction of Chloroformamides

Analysis of Monoterpenoid Indole Alkaloids Using Electrospray Ionization Tandem Mass Spectrometry

Alkaloid Biosynthesis

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