Pregnane-10,2-carbolactones from a Hawaiian Marine Sponge in the Genus <i>Myrmekioderma</i>

Four new pregnanes, 3β,4β-dihydroxy-17-methyl-17α-pregna-5,13-diene-10,2-carbolactone (<b>1</b>), 6β-chloro-3β-hydroxy-17-methyl-17α-pregna-4,13-diene-10,2-carbolactone (<b>2</b>), 3β-hydroxy-6β-methoxy-17-methyl-17α-pregna-4,13-diene-10,2-carbolactone (<b>3</b>), and 3β,6β-dihydroxy-17-methyl-17α-pregna-4,13-diene-10,2-carbolactone (<b>4</b>), were isolated from an undescribed species of <i>Myrmekioderma</i> Ehlers along with the known pregnane carbolactone (<b>5</b>). The structures of the new compounds were determined by spectroscopic methods and comparison with previously described compounds. Compound <b>5</b> showed almost 4-fold activation of pregnane X receptor, while <b>2</b> inhibited BACE1 with an IC₅₀ value of 82 μM

Neopetrocyclamines A and B, Polycyclic Diamine Alkaloids from the Sponge <i>Neopetrosia</i> cf <i>exigua</i>

Two new polycyclic alkaloids, neopetrocyclamines A and B (<b>1</b> and <b>2</b>), along with the known metabolites papuamine (<b>3</b>) and haliclonadiamine (<b>4</b>), were isolated from the Indonesian sponge <i>Neopetrosia</i> cf <i>exigua</i>. Neopetrocyclamine A contains a formamidinium moiety, a rare functional group. While these compounds share the same basic biosynthetic building blocks, the size of the ring system differs in <b>1</b> and <b>2</b> because of the formamidinium moiety. Biological evaluations of <b>1</b>–<b>4</b> revealed that papuamine is cytotoxic against glioblastoma SF-295 cells (GI₅₀ = 0.8 μM)

Isolation and Structure Determination of Two Microcystins and Sequence Comparison of the McyABC Adenylation Domains in <i>Planktothrix</i> Species

Microcystins (MCs) are toxic heptapeptides found in cyanobacteria and share the common structure <i>cyclo</i>(-d-Ala¹-l-X²-d-isoMeAsp³-l-Z⁴-Adda⁵-d-isoGlu⁶-Mdha⁷). The letters X and Z in the general formula above represent a wide range of l-amino acids that occupy positions 2 and 4, respectively. In general the variation in structural variants is due to the exchange of amino acids in position 7, 2, and 4. In the present work we report two homotyrosine (Hty)-containing microcystin variants, [d-Asp³,(<i>E</i>)-Dhb⁷]-MC-HtyY (<b>1</b>) and [d-Asp³,(<i>E</i>)-Dhb⁷]-MC-HtyHty (<b>2</b>), which were isolated from strain No80 of <i>Planktothrix rubescens.</i> Their structures were elucidated using amino acid analysis as well as 1D and 2D NMR techniques. The adenylation domains of McyABC involved in amino acid activation in positions 7, 2, and 4 of the microcystin molecule, respectively, were compared with corresponding genes of <i>Planktothrix</i> strain CYA126/8 producing [d-Asp³,Mdha⁷]-MC-RR and [d-Asp³,Mdha⁷]-MC-LR. While the adenylation domain comparison of McyAB between the two <i>Planktothrix</i> strains revealed considerable DNA recombination, the adenylation domain of McyC showed only a single amino acid substitution, which was correlated with the replacement of Arg by Hty in position 4 of the microcystin molecule

Spongiapyridine and Related Spongians Isolated from an Indonesian <i>Spongia</i> sp.

New compounds 18-nor-3,17-dihydroxyspongia-3,13(16),14-trien-2-one (<b>1</b>), 18-nor-3,5,17-trihydroxyspongia-3,13(16),14-trien-2-one (<b>2</b>), and spongiapyridine (<b>3</b>) and the known compound 17-hydroxy-4-<i>epi</i>-spongialactone A (<b>4</b>) were isolated from an Indonesian sponge of the genus <i>Spongia</i>. The structures of <b>1</b>–<b>3</b> were deduced by analyses of physical and spectroscopic data. Diterpene <b>3</b> is unusual, as the D-ring is a pyridyl ring system rather than the standard δ-lactone. The structure elucidation of this compound was complicated by facile exchange of the axial proton at the C-11 methylene with deuterium from methanol-<i>d</i>₄. The isolated compounds were tested for biological activity in a battery of in vitro assays (TNF-α-induced NFκB, LPS-induced iNOS, RXR stimulation, quinone reductase 1 induction, aromatase inhibition, TRPM7 ion channels, and aspartic protease BACE1 inhibition). Norditerpene <b>2</b> modestly inhibited aromatase with an IC₅₀ of 34 μM and induced quinone reductase 1 activity with a CD (the concentration needed to double the enzymatic response) of 11.2 μM. The remaining isolates were inactive

Streamlined Preparation and Coordination Chemistry of Hybrid Phosphine–Phosphaalkene Ligands

A rationally designed and selective synthesis of hybrid phosphine–phosphaalkene ligands <i><b>E</b></i><b>-1a</b> (Cy₂PCH₂CHPMes*, Mes* = 2,4,6-tri-<i>tert</i>-butylphenyl) and <i><b>E</b></i><b>-1b</b> (Ph₂PCH₂CHPMes*) was developed using phospha-Wittig methodology. The new hybrid ligands <i><b>E</b></i><b>-1a</b> and <i><b>E</b></i><b>-1b</b> were used to prepare the Pd and Pt dichloride complexes Pd­(Cy₂PCH₂CHPMes*)­Cl₂ (<b>2a</b>), Pd­(Ph₂PCH₂CHPMes*)­Cl₂ (<b>2b</b>), Pt­(Cy₂PCH₂CHPMes*)­Cl₂ (<b>3a</b>), and Pt­(Ph₂PCH₂CHPMes*)­Cl₂ (<b>3b</b>). The crystal structures of <i><b>E</b></i><b>-1a</b>, <i><b>E</b></i><b>-1b</b>, <b>2a</b>·1.33CHCl₃, <b>3a</b>·CH₃CN, and <b>3b</b> were determined. DFT calculations (M06/LACV3P**) on <b>2a</b> revealed that the π* orbital located on the PC unit is low-lying and accessible. An NBO analysis concluded that the phosphaalkene ligand is a significantly poorer σ donor and a slightly better π acceptor than its tertiary phosphine counterpart, due to the presence of the PC double bond

Heterocycles Derived from Generating Monovalent Pnictogens within NCN Pincers and Bidentate NC Chelates: Hypervalency versus Bell-Clappers versus Static Aromatics

Generating monovalent pnictogens within NCN pincers has resulted in the isolation of three distinct types of 1,2-azaheteroles, highly aromatic nitrogen analogues like pyrazole-based <b>5</b>, aromatic yet fluxional P- and As-derived bell-clappers <b>1</b> and <b>2</b>, and hypervalent Sb and Bi derivatives <b>3</b> and <b>4</b>, which are supported by 3-center, 4-electron N–E–N bonds. Careful analysis of the solid-state structures of <b>1</b>–<b>5/[5-Me]­[OTf]</b> in combination with NICS calculations (at the GIAO/M06/cc-pVTZ­(-PP) level) and other computational methods (NBO) suggest that simpler NC chelates may support new phosphorus- and arsenic-containing heterocycles. Indeed, reduction of ECl₂ (E = P or As) derivatives supported by <i>N</i>-Dipp (Dipp = 2,6-diisopropylphenyl) substituted NC bidentate ligands produced 1,2-benzoazaphosphole <b>11</b> and 1,2-benzoazaarsole <b>12</b>. NICS calculations revealed <b>11</b> and <b>12</b> had aromatic character on par with that of pyrazole-based <b>5</b>

Streamlined Preparation and Coordination Chemistry of Hybrid Phosphine–Phosphaalkene Ligands

A rationally designed and selective synthesis of hybrid phosphine–phosphaalkene ligands <i><b>E</b></i><b>-1a</b> (Cy₂PCH₂CHPMes*, Mes* = 2,4,6-tri-<i>tert</i>-butylphenyl) and <i><b>E</b></i><b>-1b</b> (Ph₂PCH₂CHPMes*) was developed using phospha-Wittig methodology. The new hybrid ligands <i><b>E</b></i><b>-1a</b> and <i><b>E</b></i><b>-1b</b> were used to prepare the Pd and Pt dichloride complexes Pd­(Cy₂PCH₂CHPMes*)­Cl₂ (<b>2a</b>), Pd­(Ph₂PCH₂CHPMes*)­Cl₂ (<b>2b</b>), Pt­(Cy₂PCH₂CHPMes*)­Cl₂ (<b>3a</b>), and Pt­(Ph₂PCH₂CHPMes*)­Cl₂ (<b>3b</b>). The crystal structures of <i><b>E</b></i><b>-1a</b>, <i><b>E</b></i><b>-1b</b>, <b>2a</b>·1.33CHCl₃, <b>3a</b>·CH₃CN, and <b>3b</b> were determined. DFT calculations (M06/LACV3P**) on <b>2a</b> revealed that the π* orbital located on the PC unit is low-lying and accessible. An NBO analysis concluded that the phosphaalkene ligand is a significantly poorer σ donor and a slightly better π acceptor than its tertiary phosphine counterpart, due to the presence of the PC double bond

Synthesis of a Tris(phosphaalkene)phosphine Ligand and Fundamental Organometallic Reactions on Its Sterically Shielded Metal Complexes

A new tris­(phosphaalkene)­phosphine ligand (<b>1</b>) was synthesized via phospha-Wittig methodology. Metalation of <b>1</b> with [RhCl­(C₂H₄)₂]₂ and [IrCl­(COE)₂]₂ (COE = cyclooctene) produced trigonal bipyramidal metal chlorides <b>2a</b> (M = Rh) and <b>2b</b> (M = Ir) in which the ligand coordinates in a tetradentate fashion. X-ray crystallographic studies on <b>1</b>·1.5THF, <b>2a</b>·5CHCl₃, and <b>2b</b>·2.5CHCl₃ combined with DFT calculations revealed a pronounced change in hybridization of the phosphaalkene phosphorus atoms upon coordination to the Rh/Ir centers, resulting in highly sterically congested metal complexes. Nucleophilic substitution on <b>2a</b> with NaN₃ afforded Rh–N₃ complex <b>3</b>; computational analysis, IR spectroscopy, and ¹⁵N­{¹H} NMR spectroscopy on isotopologue ^<b>15</b><b>N-3</b> provided additional structural insights. Halide abstraction of the chloride in <b>2b</b> with AgOTf in the presence of acetonitrile afforded cationic Ir–NCMe complex <b>4</b>. Evidence of the bound acetonitrile unit was obtained by 2D NMR spectroscopy and deuterium labeling studies