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Dimeric indole and quinolinone alkaloidsRutherford, M. J. January 1985 (has links)
No description available.
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Enantiospecific approaches to indole alkaloidsHollinshead, S. P. January 1987 (has links)
No description available.
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A novel approach to the total synthesis of corynanthe indole alkaloids via cyclopentanoid intermediariesWingfield, M. January 1985 (has links)
No description available.
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Synthetic studies towards aspidospermidineSharpe, Andrew January 1995 (has links)
No description available.
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A novel method for the synthesis of Indolo[2,1-a]isoquinolines and modelling studies of 3-substituted oxindoles against PfPK5Sello, Thato Saoeni 08 September 2008 (has links)
Many naturally occurring and synthetically made azapolycyclic aromatic ring
systems display important biological activities. One class of naturally occurring
azapolycyclic aromatic ring systems is the dibenzopyrrocoline alkaloids, made
from an indole nucleus fused to an isoquinoline system sharing the same
nitrogen, i.e. the indolo[2,1-a]isoquinoline nucleus. The indolo[2,1-a]isoquinoline
and its analogues have been reported to possess antileukemic, tubulin
polymerization inhibitory and antitumor activity.
A variety of indolo[2,1-a]isoquinolines have been synthesized in our labs. This
includes, the 5,12-dimethyl-6-phenylindolo[2,1-a]isoquinoline, using the Suzuki-
Miyaura cross-coupling reaction and reaction conditions for the formation of
aromatic rings (KOBut in DMF) developed in our laboratories. In this dissertation,
we outline the syntheses of (±)-5,6-dihydro-6-phenylindolo[2,1-a]isoquinolin-5-ol
and 2-(1-benzyl-1H-benzo[d]imidazol-2-yl)benzaldehyde. We also discuss the
synthesis and the modelling studies, (docked in silico) of the 3-substituted
oxindoles in the X-ray crystal structure of the PfPK5 cyclin dependent kinase
(CDK).
The synthesis of indolo[2,1-a]isoquinolines started with N-protection of isatin and
benzimidazole with a benzyl group to afford 1-benzylindoline-2,3-dione and 1-
benzyl-1H-benzo[d]imidazole, respectively. The next step was the synthesis of
the brominated compound, 1-benzyl-2-bromo-1H-indole, and the iodated
compound, 1-benzyl-2-iodo-1H-benzo[d]imidazole. 1-Benzyl-2-bromo-1H-indole
was synthesized by means of a functional group interconversion of the oxygen in
the 3-position of isatin to two chlorine atoms initially, followed by removal of those
chlorine atoms with activated zinc, followed by the conversion of the carbonyl of
the oxindole to give a 2-bromoindole using POBr3. 1-Benzyl-2-iodo-1Hbenzo[
d]imidazole was synthesized in two ways. Firstly, 1-benzyl-1Hbenzo[
d]imidazole was exposed to LDA followed by iodinating the 2-position by
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exposure of the intermediate to diiodoethane. The second method uses a
halogenating method developed in our labs. 1-Benzyl-1H-benzo[d]imidazole was
exposed to isopropylmagnesium chloride lithium chloride followed by I2. Having
obtained the halogenated products, both sets of halogenated precursors were
coupled with 2-formylphenylboronic acid using the Suzuki-Miyaura crosscoupling
reaction to obtain the products, 2-(1-benzyl-1H-indol-2-yl)benzaldehyde
and 2-(1-benzyl-1H-benzo[d]imidazol-2-yl)benzaldehyde in 98 and 67% yield,
respectively. Aromatization of 2-(1-benzyl-1H-indol-2-yl)benzaldehyde occurred
easily using tBuOK in DMF at room temperature to afford (±)-5,6-dihydro-6-
phenylindolo[2,1-a]isoquinolin-5-ol in 75% yield (7:3 ratio of anti-: syn-) but
exposing 2-(1-benzyl-1H-benzo[d]imidazol-2-yl)benzaldehyde to the same
reaction conditions did not afford the desired product. Dehydrating (±)-5,6-
dihydro-6-phenylindolo[2,1-a]isoquinolin-5-ol using methanesulfonyl chloride in
CH2Cl2 was unsuccessful. Further attempts at dehydrating (±)-5,6-dihydro-6-
phenylindolo[2,1-a]isoquinolin-5-ol were prevented due to time constraints.
In the last part of the project, a library of 3-substituted oxindoles (13 molecules)
was synthesized successfully and the compounds were docked in silico in the
active site of an X-ray crystal structure of PfPK5, a cyclin dependent kinase of
the Plasmodium falciparum, the agent causing the most severe form of human
malaria. Eleven of the thirteen compounds were synthesized by condensation of
oxindole and a suitable aldehyde in the presence of piperidine. The other two, 3-
(propan-2-ylidene)indolin-2-one and 5,6-dimethoxy-3-(methylthio)indolin-2-one,
were synthesized differently. 3-(Propan-2-ylidene)indolin-2-one was synthesized
by reacting the oxindole with acetone in the presence of HCl and 5,6-dimethoxy-
3-(methylthio)indolin-2-one was synthesized following Gassman’s methodology.
Two molecules scored well in the molecular modelling studies using the X-ray
crystal structure of PfPK5, namely, (E/Z)-3-(3,4-dimethoxybenzylidene)indolin-2-
one and (Z)-3-(4-hydroxybenzylidene)indolin-2-one.
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In conclusion, we managed to synthesize (±)-5,6-dihydro-6-phenylindolo[2,1-
a]isoquinolin-5-ol using the Suzuki Miyaura cross-coupling reaction and reaction
conditions that lead to aromatization (tBuOK in DMF at room temperature) as key
steps and 2-(1-benzyl-1H-benzo[d]imidazol-2-yl)benzaldehyde using the Suzuki-
Miyaura cross-coupling reaction. A library of 3-substituted oxindoles was made
and using molecular modelling were docked in silico into the crystal structure of
the active site of PfPK5 with 2 compounds showing promise, for further studies.
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Total synthesis of indole alkaloids: pt. 1. Asymmetric synthesis of (-)-ibogamine. pt. 2. An approach toward the synthesis of koumineChoi, Younggi 04 February 2003 (has links)
PART I. The preparation of (-)-ibogamine (1) in fourteen steps from
benzoquinone and in 10% overall yield is a powerful illustration of the value of
the asymmetric Diels-Alder reaction as a starting point in a multistep synthesis.
All four cycloadducts, 70, 77, 84 and 96, obtained with the (S)-BINOL-TiCl���
complex were found to have the same absolute configuration. Furthermore, they
are in the same enantiomeric series that Mikami observed with 1,4-naphthoquinone using the same catalyst, lending confidence to future stereochemical predictions that may be made with this system.
PART II. Three different routes for the synthesis of the
hexahydroisoquinoline 98 met obstacles which defeated our approach to
koumine. The Diels-Alder reaction of cyclic 1-azadienes 102 and 108 was
abandoned due to the lack of reactivity of the dienes. An anionic oxy-Cope
rearrangement of the azabicyclo[2.2.2]octane system caused mainly
decomposition of the starting materials. Finally, an intramolecular [2+2]
photocycloaddition generated "crossed", "straight" and hydroisoquinoline
products in varying ratios, depending on the substituent pattern of the substrate,
but this approach was not synthetically useful. The results from this last study
may be valuable for predicting the regiochemical outcome of certain
intramolecular photocycloadditions. / Graduation date: 2003
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Modulation of chemically-induced hepatocarcinogenesis by indole-3-carbinol : mechanisms and species comparisonOganesian, Aram 25 November 1997 (has links)
There is plenty of evidence from epidemiology studies
supporting a link between certain components in the human
diet and cancer incidence. It is estimated that 3-4 million
annual cases of cancer could be prevented worldwide just by
changing dietary habits. In parts of the world where
vegetables and fruits constitute a large part of the diet,
certain cancer incidences are markedly lower compared to
Western countries. In particular, consumption of cruciferous
vegetables is negatively associated with occurrence of
certain cancers. One of the compounds from crucifers that is
implicated in chemoprevention, is indole-3-carbinol(I3C),
documented to inhibit tumor formation in several tissues in
rodents, including the mammary tissue. I3C and is currently
being evaluated in several clinical trials as a
chemopreventive agent against breast cancer in humans. There
are, however, some legitimate concerns regarding the use of
Pure I3C since, depending upon conditions of administration,
I3C can act as a promoter of hepatocarcinogenesis. Evidence
is presented here that dietary I3C can promote and/or
enhance liver tumor formation in rainbow trout (supporting
earlier reports in literature) and the C57BL/6J mouse
(enhancement in short-term pre-initiation exposure through
lactational transfer, inhibition in a long-term post-initiation
feeding study). I3C is also reported to promote
in the rat liver model. A major concern associated with
dietary I3C supplementation relates to its estrogenic
effects as seen in trout and also its ability to induce
certain cytochrome P-450s involved in procarcinogen
activation. Biological effects of I3C are attributed to its
acid condensation products. It was observed in this study that
I3C acts through different mechanisms, including the Ah
receptor-mediated and estrogenic pathways. Understanding of
the role of I3C derivatives in beneficial and/or hazardous
effects resulting from dietary exposure will be crucial in
evaluating the promise of I3C as a chemoprevention agent.
Questions pertaining to the risk/benefit of the use of dietary
I3C supplementation for preventing estrogen-related diseases,
without increasing the risk of promotion of
hepatocarcinogenesis in humans, may depend on whether the
mechanism(s) of action of I3C derivatives in humans is more
like the adult mouse or the neonatal mouse, rat and trout. / Graduation date: 1998
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Degradation of N-heterocyclic aromatics indole and 2-methylindole by bacteria from wetland sediment and characterization of the bacteria involvedYip, Choi-wan, January 2005 (has links)
Thesis (M. Phil.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.
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Synthèse et évaluation pharmacologique de peptidomimétiques à structure indoliques antagonistes potentiels de la LHRHPuget, Alain Le Baut, Guillaume. January 2003 (has links) (PDF)
Thèse doctorat : Pharmacie. Chimie thérapeutique : Université de Nantes : 2003. / Bibliogr. f. 188-195.
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Nouvelles synthèses de dérivés hetérocycliques pour applications biologiques (Céphalosporines, Coumarines et Indoles) = New synthesis of heterocyclic derivatives for biological applications (Cephalosporins, Coumarins and Indoles) /Rodriguez Dominguez, Juan Carlos Kirsch, Gilbert. Prieto, Sylvia. January 2006 (has links) (PDF)
Thèse de doctorat : Synthèse organique : Metz : 2006. / Thèse soutenue sur ensemble de travaux. Bibliogr. p. 98 -108.
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