Direct Stereoselective Synthesis of Enantiomerically Pure <i>anti</i>-β-Amino Alcohols

Enantiomerically pure <i>anti</i>-β-amino alcohols were synthesized from optically pure α-(<i>N</i>,<i>N</i>-dibenzylamino)­benzyl esters, derived from α-amino acids, by the sequential reduction to aldehyde with DIBAL-H at −78 °C and subsequent in situ addition of Grignard reagents. Besides <i>anti</i>-β-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 (60–95%) 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. (−)-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(PPh₃)₂(HdmoPTA)](OSO₂CF₃)₂ (HdmoPTA = 3,7‑<i>H</i>‑3,7-Dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)

The complex [RuCp­(PPh₃)₂(HdmoPTA)]­(OSO₂CF₃)₂ (<b>2</b>; HdmoPTA = 3,7-<i>H</i>-3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo­[3.3.1]­nonane) 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 platinum­(II)–guanidine complexes with anticancer activity was studied. To this end, an atom-economical catalytic approach was followed by using ZnEt₂ to catalyze the addition of aminoferrocene and 4-ferrocenylaniline to <i>N</i>,<i>N</i>′-diisopropylcarbodiimide. Furthermore, reaction of a platinum­(II) source with the newly obtained guanidines Fc–NC­(NHⁱPr)₂ (<b>3</b>) and Fc­(1,4-C₆H₄)–NC­(NHⁱPr)₂ (<b>4</b>) provided access to the heterometallic complexes [PtCl₂{Fc–NC­(NHⁱPr)₂}­(DMSO)] (<b>5</b>), [PtCl₂{Fc­(1,4-C₆H₄)–NC­(NHⁱPr)₂}­(DMSO)] (<b>6</b>), and [PtCl₂{Fc­(1,4-C₆H₄)–NC­(NHⁱPr)₂}₂] (<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 Fe–Pt complexes <b>5</b> and <b>6</b> are active against all human cancer cell lines tested, with GI₅₀ values in the range 1.4–2.6 μM, 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 A–F (<b>1</b>–<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>–<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 GI₅₀ values ranging from 19 to >100 μM

Reactivity and Biological Properties of a Series of Cytotoxic PtI₂(amine)₂ Complexes, Either <i>cis</i> or <i>trans</i> Configured

Six diiodido–diamine platinum­(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 Pt­(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 PtI₂(amine)₂ Complexes, Either <i>cis</i> or <i>trans</i> Configured

Six diiodido–diamine platinum­(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 Pt­(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