General strategies for alkaloid synthesis via intramolecular [4 + 2] cycloadditions of enamides. Application to the formal total synthesis of racemic lycorine

Martin, Stephen F.; Tu, Chih yun

doi:10.1021/jo00331a049

Cited by 28 publications

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“…Narciclasine [1} and lycorine [16} were obtained by extraction of the bulbs of Nar- cissus incomparabilis (31). Syntheses have been reported for (+)-lycoricidine (32,33), for racemic lycorine (34)(35)(36)(37)(38), and pancratistatin (8) as well as for the isonarciclasines 13a and 13b (39)(40)(41)). An elegant, highly-convergent synthesis of racemic lycorine has been reported (42) based in part upon synthetic strategy described by Stork and Morgans (43).…”

Section: Resultsmentioning

confidence: 99%

Antiviral (RNA) Activity of Selected Amaryllidaceae Isoquinoline Constituents and Synthesis of Related Substances

et al. 1992

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A series of 23 Amaryllidaceae isoquinoline alkaloids and related synthetic analogues were isolated or synthesized and subsequently evaluated in cell culture against the RNA-containing flaviviruses (Japanese encephalitis, yellow fever, and dengue viruses), bunyaviruses (Punta Toro, sandfly fever, and Rift Valley fever viruses), alphavirus (Venezuelan equine encephalomyelitis virus), lentivirus (human immunodeficiency virus-type 1) and the DNA-containing vaccinia virus. Narciclasine [1], lycoricidine [2], pancratistatin [4], 7-deoxypancratistatin [5], and acetates 6-8, isonarciclasine [13a], cis-dihydronarciclasine [14a], trans-dihydronarciclasine [15a], their 7-deoxy analogues 13b-15b, lycorines 16 and 17, and pretazettine [18] exhibited consistent in vitro activity against all three flaviviruses and against the bunyaviruses, Punta Toro and Rift Valley fever virus. Activity against sandfly fever virus was only observed with 7-deoxy analogues. In most cases, however, selectivity of the active compounds was low, with toxicity in uninfected cells (TC50) occurring at concentrations within 10-fold that of the viral inhibitory concentrations (IC50). No activity was observed against human immunodeficiency virus-type 1, Venezuelan equine encephalomyelitis virus, or vaccinia viruses. Pancratistatin [4] and its 7-deoxy analogue 5 were evaluated in two murine Japanese encephalitis mouse models (differing in viral dose challenge, among other factors). In two experiments (low LD50 viral challenge, variant I), prophylactic administration of 4 at 4 and 6 mg/kg/day (2% EtOH/saline, sc, once daily for 7 days, day -1 to +5) increased survival of Japanese-encephalitis-virus-infected mice to 100% and 90%, respectively. In the same model, prophylactic administration of 5 at 40 mg/kg/day in hydroxypropylcellulose (sc, once daily for 7 days, day -1 to +5) increased survival of Japanese-encephalitis-virus-infected mice to 80%. In a second variant (high LD50 viral challenge), administration of 4 at 6 mg/kg/day (ip, twice daily for 9 days, day -1 to +7) resulted in a 50% survival rate. In all cases, there was no survival in the diluent-treated control mice. Thus, 4 and 5 demonstrated activity in mice infected with Japanese encephalitis virus but only at near toxic concentrations. To our knowledge, however, this represents a rare demonstration of chemotherapeutic efficacy (by a substance other than an interferon inducer) in a Japanese-encephalitis-virus-infected mouse model.

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Section: Resultsmentioning

confidence: 99%

Antiviral (RNA) Activity of Selected Amaryllidaceae Isoquinoline Constituents and Synthesis of Related Substances

et al. 1992

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“…In our cases only polar, intractable mixtures were obtained. Other conditions employed with similar results included: heating at 150°C in polyphosphoric acid; 15 treating with POCl 3 in refluxing benzene; 16 or reacting with Eaton's acid (P 2 O 5 / MeSO 3 H). 17 From the 1 H NMR spectra of the crude reaction products it was obvious that the benzyl protecting group was not inert to the relatively harsh reagents and reaction temperature conditions that were required to effect the Bischler-Napieralski cyclization.…”

Section: Figurementioning

confidence: 99%

An Efficient Synthesis of Thalifoline

Youchu¹,

Georghiou²

2002

Synthesis

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“…A more convenient route to ortho-quinodimethanes, which requires much milder conditions than that from benzocyclobutenes, is by elimination from suitable ortho-silylmethylbenzylammonium salts induced by fluoride ion. The quinodimethane (141), for example, generated in the presence of dimethyl fumarate gave the adduct ( 142 Similarly, the precursor (143) gave oestrone methyl ether (144) in 86% yield in a stereoselective reaction (see also ref. 137) and in a novel route to 11-oxygenated steroids, the 11-ketotestosterone derivative (147) was obtained by ozonization of the tetracyclic precursor (146) itself formed stereoselectively by intramolecular Diels-Alder cycli~ation'~~ of (145).…”

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confidence: 99%

Chapter 13. Synthetic methods

Carruthers¹

1981

Annu. Rep. Prog. Chem., Sect. B

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The pace of advance in organic synthesis makes it impossible to include more than a selection of recent methods in this Report. A number of important topics, for example oxidation and reduction, have been omitted (but not forgotten), and it is hoped that it may be possible to include some of these in next year's Report. AlcoholsAn extremely simple, convenient, and selective method for acetylating primary alcohols in the presence of secondary ones has been reported,' and has been applied in the carbohydrate series.* Primary hydroxyalkylphenols are thus converted into acetoxyalkylphenols and primary aromatic amines into the corresponding acetamides. t-Butyldimethylsilyl, tri-isopropylsilyl, and octadecyldimethylsilyl triflates are useful reagents for silylation of hindered alcohols which react sluggishly with the usual silylating agent^.^ 1,2-and 1,3-diols are conveniently protected by conversion into their di-t-butylsilylene derivatives by reaction with di-t-butyldichlorosilane. The protecting group is easily removed by treatment with pyridinium hydr~fluoride.~The de-oxygenation of secondary alcohols by radical reduction of thiocarbonyl esters has been shown to be a general reaction of value in the synthesis and modification of natural products.' By appropriate modification of experimental conditions the reaction has now been extended to primary alcohols.6 A modified Barton procedure was used to convert ribonucleosides into 2'-deoxyn~cleosides.~ Methods for the inversion of secondary alcohols are valuable in synthesis. Caesium carboxylates in dimethyl formamide are good nucleophiles and are useful for the introduction of hydroxy-substituents by SN2 nucleophilic substitution. In practice the best results were obtained with the propionate. Mesylates of several secondary alcohols were cleanly converted into the propionates of the inverted alcohol in high yield in warm dimethyl formamide. The inversion of (S)-2-octanol,

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General strategies for alkaloid synthesis via intramolecular [4 + 2] cycloadditions of enamides. Application to the formal total synthesis of racemic lycorine

Cited by 28 publications

References 0 publications

Antiviral (RNA) Activity of Selected Amaryllidaceae Isoquinoline Constituents and Synthesis of Related Substances

Antiviral (RNA) Activity of Selected Amaryllidaceae Isoquinoline Constituents and Synthesis of Related Substances

An Efficient Synthesis of Thalifoline

Chapter 13. Synthetic methods

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