8 research outputs found
Direct Stereoselective Synthesis of Enantiomerically Pure <i>anti</i>-Ī²-Amino Alcohols
Enantiomerically pure <i>anti</i>-Ī²-amino alcohols
were synthesized from optically pure Ī±-(<i>N</i>,<i>N</i>-dibenzylamino)Ābenzyl esters, derived from Ī±-amino
acids, by the sequential reduction to aldehyde with DIBAL-H at ā78
Ā°C and subsequent in situ addition of Grignard reagents. Besides <i>anti</i>-Ī²-amino alcohols, <i>anti-</i>2<i>-</i>amino<i>-</i>1,3-diols and <i>anti</i>-3-amino-1,4-diols were obtained in good yields (60ā95%) and
excellent stereoselectivity (de > 95%). Our technique is compatible
with free hydroxyl groups present in the substrate. To demonstrate
the versatility of the method, spisulosine and sphinganine were synthesized
in two steps from the appropriate <i>N</i>,<i>N</i>-dibenzyl-l-aminobenzyl ester in 42% and 45% yield, respectively
Synthesis of Luffarin L and 16-<i>epi</i>-Luffarin L Using a Temporary Silicon-Tethered Ring-Closing Metathesis Reaction
The
first synthesis of luffarin L (<b>1</b>) and 16-<i>epi</i>-luffarin L (<b>2</b>) by a silicon-tethered ring
closing metathesis as a key step has been achieved. The stereochemistry
and absolute configuration of the natural sesterterpenolide luffarin
L (<b>1</b>) and a new route for the stereoselective synthesis
of sesterterpenolides with a luffarane skeleton have been established
Biomimetic Synthesis of Two Salmahyrtisanes: Salmahyrtisol A and Hippospongide A
Sesterterpenes with a salmahyrtisane
skeleton have been synthesized
for the first time. (ā)-Sclareol has been selected as a precursor
for the synthesis of two novel natural products: salmahyrtisol A (<b>1</b>) and hippospongide A (<b>2</b>). Our results represent
a biomimetic approach to obtaining salmahyrtisanes from hyrtiosanes.
Salmahyrtisol A has shown an activity comparable to that of the standard
anticancer drugs in the cell lines A549, HBL-100, HeLa, and SW1573
Synthesis and Antiproliferative Activity of [RuCp(PPh<sub>3</sub>)<sub>2</sub>(HdmoPTA)](OSO<sub>2</sub>CF<sub>3</sub>)<sub>2</sub> (HdmoPTA = 3,7ā<i>H</i>ā3,7-Dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)
The complex [RuCpĀ(PPh<sub>3</sub>)<sub>2</sub>(HdmoPTA)]Ā(OSO<sub>2</sub>CF<sub>3</sub>)<sub>2</sub> (<b>2</b>; HdmoPTA = 3,7-<i>H</i>-3,7-dimethyl-1,3,7-triaza-5-phosphabicycloĀ[3.3.1]Ānonane)
was synthesized and characterized. Its crystal structure was determined
by single-crystal X-ray diffraction. The complex showed a more potent
antiproliferative activity than cisplatin against a representative
panel of human cancer cells
Catalytically Generated Ferrocene-Containing Guanidines as Efficient Precursors for New Redox-Active Heterometallic Platinum(II) Complexes with Anticancer Activity
The
potential of structurally new ferrocene-functionalized guanidines
as redox-active precursors for the synthesis of heterometallic platinumĀ(II)āguanidine
complexes with anticancer activity was studied. To this end, an atom-economical
catalytic approach was followed by using ZnEt<sub>2</sub> to catalyze
the addition of aminoferrocene and 4-ferrocenylaniline to <i>N</i>,<i>N</i>ā²-diisopropylcarbodiimide. Furthermore,
reaction of a platinumĀ(II) source with the newly obtained guanidines
FcāNī»CĀ(NH<sup>i</sup>Pr)<sub>2</sub> (<b>3</b>) and FcĀ(1,4-C<sub>6</sub>H<sub>4</sub>)āNī»CĀ(NH<sup>i</sup>Pr)<sub>2</sub> (<b>4</b>) provided access to the heterometallic
complexes [PtCl<sub>2</sub>{FcāNī»CĀ(NH<sup>i</sup>Pr)<sub>2</sub>}Ā(DMSO)] (<b>5</b>), [PtCl<sub>2</sub>{FcĀ(1,4-C<sub>6</sub>H<sub>4</sub>)āNī»CĀ(NH<sup>i</sup>Pr)<sub>2</sub>}Ā(DMSO)] (<b>6</b>), and [PtCl<sub>2</sub>{FcĀ(1,4-C<sub>6</sub>H<sub>4</sub>)āNī»CĀ(NH<sup>i</sup>Pr)<sub>2</sub>}<sub>2</sub>] (<b>7</b>). Electrochemical studies evidence the remarkable
electronic effect played by the direct attachment of the guanidine
group to the ferrocene moiety in <b>3</b>, making its one-electron
oxidation extremely easy. Guanidine-based FeāPt complexes <b>5</b> and <b>6</b> are active against all human cancer cell
lines tested, with GI<sub>50</sub> values in the range 1.4ā2.6
Ī¼M, and are more cytotoxic than cisplatin in the resistant T-47D
and WiDr cell lines
<i>ent</i>-Labdane Diterpenoids from the Aerial Parts of <i>Eupatorium obtusissmum</i>
Six new <i>ent</i>-labdane
diterpenoids, uasdlabdanes
AāF (<b>1</b>ā<b>6</b>), were isolated from
the aerial parts of <i>Eupatorium obtusissmum</i>. The new
structures were elucidated through spectroscopic and spectrometric
data analyses. The absolute configurations of compounds <b>1</b> and <b>2</b> were established by X-ray crystallography, and
those of <b>3</b>ā<b>6</b>, by comparison of experimental
and calculated electronic circular dichroism spectra. The antiproliferative
activity of the compounds was studied in a panel of six representative
human solid tumor cell lines and showed GI<sub>50</sub> values ranging
from 19 to >100 Ī¼M
Reactivity and Biological Properties of a Series of Cytotoxic PtI<sub>2</sub>(amine)<sub>2</sub> Complexes, Either <i>cis</i> or <i>trans</i> Configured
Six diiodidoādiamine platinumĀ(II) complexes, either <i>cis</i> or <i>trans</i> configured, were prepared,
differing only in the nature of the amine ligand (isopropylamine,
dimethylamine, or methylamine), and their antiproliferative properties
were evaluated against a panel of human tumor cell lines. Both series
of complexes manifested pronounced cytotoxic effects, with the <i>trans</i> isomers being, generally, more effective than their <i>cis</i> counterparts. Cell cycle analysis revealed different
modes of action for these new PtĀ(II) complexes with respect to cisplatin.
The reactivity of these platinum compounds with a number of biomolecules,
including cytochrome c, two sulfur containing modified amino acids,
9-ethylguanine, and a single strand oligonucleotide, was analyzed
in depth by mass spectrometry and NMR spectroscopy. Interestingly,
significant differences in the reactivity of the investigated compounds
toward the various model biomolecules were observed: in particular
we observed that <i>trans</i> complexes preferentially release
their iodide ligands upon biomolecule binding, while the <i>cis</i> isomers may release the amine ligands with retention of iodides.
Such differences in reactivity may have important mechanistic implications
and a relevant impact on the respective pharmacological profiles
Reactivity and Biological Properties of a Series of Cytotoxic PtI<sub>2</sub>(amine)<sub>2</sub> Complexes, Either <i>cis</i> or <i>trans</i> Configured
Six diiodidoādiamine platinumĀ(II) complexes, either <i>cis</i> or <i>trans</i> configured, were prepared,
differing only in the nature of the amine ligand (isopropylamine,
dimethylamine, or methylamine), and their antiproliferative properties
were evaluated against a panel of human tumor cell lines. Both series
of complexes manifested pronounced cytotoxic effects, with the <i>trans</i> isomers being, generally, more effective than their <i>cis</i> counterparts. Cell cycle analysis revealed different
modes of action for these new PtĀ(II) complexes with respect to cisplatin.
The reactivity of these platinum compounds with a number of biomolecules,
including cytochrome c, two sulfur containing modified amino acids,
9-ethylguanine, and a single strand oligonucleotide, was analyzed
in depth by mass spectrometry and NMR spectroscopy. Interestingly,
significant differences in the reactivity of the investigated compounds
toward the various model biomolecules were observed: in particular
we observed that <i>trans</i> complexes preferentially release
their iodide ligands upon biomolecule binding, while the <i>cis</i> isomers may release the amine ligands with retention of iodides.
Such differences in reactivity may have important mechanistic implications
and a relevant impact on the respective pharmacological profiles