Structures and cytotoxic properties of sponge-derived bisannulated acridines

A reinvestigation of sponge natural products from additional Indo-Pacific collections of Xestospongiacf. carbonaria and X. cf. exigua has provided further insights on the structures, biological activities, and biosynthetic origin of bisannulated acridines. These alkaloids include one known pyridoacridine, neoamphimedine (2), and three new analogues, 5-methoxyneoamphimedine (4), neoamphimedine Y (5), and neoamphimedine Z (6). A completely new acridine, alpkinidine (7), was also isolated. A disk diffusion soft agar assay, using a panel of five cancer cell lines (solid tumors and leukemias) and two normal cells, was used to evaluate the differential cytotoxicity (solid tumor selectivity) of the sponge semipure extracts and selected compounds including amphimedine (1), 2, 4, and 7. While all four compounds were solid tumor selective, 1 and 2 were the most potent and 4 was the most selective. The rationale used to characterize the new structures is outlined along with the related biosynthetic pathways envisioned to generate 2 and 7.     

A short synthetic route to the calystegine alkaloids

An efficient strategy is described for the synthesis of enantiopure calystegine alkaloids. The key step employs a zinc-mediated fragmentation of benzyl-protected methyl 6-iodo-glycosides followed by in situ formation of the benzyl imine and Barbier-type allylation with zinc, magnesium, or indium metal. Stereochemistry in the pivotal allylation is controlled by the choice of the metal. The functionalized 1,8-nonadienes, thus formed, are converted into cycloheptenes by ring-closing olefin metathesis. Regioselective hydroboration and oxidation give the corresponding cycloheptanones, which are deprotected to afford the desired calystegines. Hereby, calystegine B(2), B(3), and B(4) are prepared from D-glucose, D-galactose, and D-mannose, respectively. This route constitutes the shortest synthesis of calystegine B(2) and gives rise to the first total syntheses of calystegine B(3) and B(4).     

Structural studies in main group chemistry : XIX. Organotin(IV) derivatives of tetracyanoethylene, 7,7,8,8-tetracyanoquinodimethane and 2,3,5,6-tetrachlorobenzoquinone. The isolation of stable organotin-substituted radicals

The reaction of organotin chlorides with the lithium salt of 7,7,8,8-tetracyanoquinodimethane (TCNQ) or hexaalkylditins with TCNQ yield stable organotin-substituted free radicals of the types R₃SnTCNQ^. (R = Me, n-Pr, n-Bu) and Me₂Sn(TCNQ^.)₂. The reaction of hexaphenylditin with TCNQ yields a (σ → π) charge transfer complex of stoichiometry (Ph₃SnSnPh₃)·TCNQ, whilst [Me₂SnCl(terpyridyl)⁺](TCNQ^-·) was isolated from the reaction of [Me₂SnCl(terpyridlyl)⁺][Me₂SnCl₃^-] and LiTCNQ. The oxidation of hexaalkylditins by tetracyanoethylene (TCNE) yields stable free radicals of the type R₃SnTCNE·, but treatment with 2,3,5,6-tetrachlorobenzoquinone yields either R₃SnOC₆Cl₄O·-p (R = Me) or R₃SnOC₆Cl₄OSnR₃-p (R = n-Bu, Ph). Tin-119 Mössbauer spectroscopy shows that the derivatives R₃SnTCNQ· and R₃TCNE· have trigonally-bipyramidally coordinated tin with planar [SnC₃] skeletons and bridging [TCNQ·] and [TCNE·] groups forming infinite one-dimensional chain structures. Me₃SnOC₆Cl₄O·-p was inferred to possess a similar structure but with oxy bridges forming chains with a Sn---O---Sn---O backbone. Me₂Sn(TCNQ·)₂ has a structure intermediate between tetrahedral and octahedral with a non-linear MeSnMe unit and anisobidentate chelation by two TCNQ groups. The TCNQ derivatives were of two types: (i) “green” or “brown”, indicative of delocalisation of the Ione electron over the cyanoquinone ligand, and (ii) a “blue” form in which spin-pairing of the Ione electron between adjacent organic groups takes place. Me₃SnTCNQ· may exist in both forms depending upon the mode of preparation.     

Neutral solvent/crown ether interactions 3. Reorientation of the hydrogen bonds in the low temperature (−150°C) structure of 18-crown-6·2(CH3NO2)

The title complex was crystallized from a saturated solution of 18-crown-6 in nitromethane at 5°C and cooled to –150°C prior to X-ray diffraction data collection. At –150° C 18-crown-6·2(CH₃NO₂) is monoclinic,P2₁/_n witha=9.290(2),b=7.864(6),c=13.627(8) Å, =1000.84(4)° andD _calc=1.31 g cm^–3 for Z=2. Leastsquares refinement using 1521 independent observed reflections [F _o5(F _o)] led to a final conventionalR value of 0.041. The complex at –150°C is isostructural with its room temperature structure with the exception of the orientation of the methyl hydrogen atoms and their crown ether oxygen interactions. The methyl group hydrogen atoms were fully refined isotropically. The crown ether resides around a center of inversion and hasD _3d symmetry. There is one methyl hydrogen...crown interaction at 2.35(3) Å, one apparently bifurcated hydrogen bond utilizing a second methyl hydrogen atom (2.55(3), 2.65(3) Å) and the third hydrogen atom is actually directed away from the crown ring (closest H...O contact=2.67(3) Å). Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82048 (5 pages).For part 2, see reference [24].     

Synthesis of the tetrahydroisoquinoline alkaloid (+/-)-renieramycin G and A (+/-)-lemonomycinone analogue from a common intermediate

The total synthesis of tetrahydroisoquinoline alkaloids (+/-)-renieramycin G (4) and a lemonomycinone analogue (7) is described. A general strategy to synthesize both the mono- and bistetrahydroisoquinoline alkaloids from a common advanced intermediate, 17, is presented.     

An ab initio structural and vibrational analysis of gauche,trans,trans- and gauche,cis,trans-hexa-1,3,5-trienes

The results of complete geometry optimizations of the high energy stable gauche,Trans,trans- and gauche,Cis,trans- rotamers of hexa-1,3,5-trienes are reported at the RHF/6-31G//RHF/B-31G level. The angles of rotation around one of the single C-C bonds are found to be 33.7° and 45.5°, respectively. The corresponding harmonic force fields of these molecules are also reported at this level and corrected using scale factors transferred from buta 1,3-diene. Aspecial scale factor was used for the central C=C double bond stretching coordinate to take into account vibronic coupling. The theoretical vibrational frequencies, calculated with the scaled quantum mechanical (SQM) force fields, allow a complete interpretation of the experimental vibrational spectra of these molecules.Preliminary results were reported at the Austin XII Symposium on Molecular Structure, Austin, TX, February 28 through March 3, 1988, S 18, p. 111 (USA) and at the XIXth European Congress on Molecular Spectroscopy, Dresden, September 4 through September 8, 1989, p. 226 (GDR).     

Stokes/anti-stokes intensity ratio in the resonance region

Relative intensities of the Stokes and anti-Stokes Raman lines associated with the I-I stretching mode of I₂ and symmetric stretching mode of MnO^?₄ are presented. The data indicate that the maxima in the excitation profile of the anti-Stokes scattering are shifted from those of the Stokes scattering. The experimental Stokes/anti-Stokes intensity ratios agree with the theoretical values obtained with parameters from the electronic absorption spectra.     

Inter- and intramolecular pi-stacking interactions in cis-bis[1-(9-anthracene)]phosphirane complexes of platinum(II)

The bis[1-(9-anthracene)phosphirane]dithiolatoplatinum(II) complexes, Pt[1-(9-anthracene)phosphirane](2)(dithiolate), where dithiolate = 1,1-dimethoxycarbonyl-ethylene-2,2-dithiolate (dmdt) (2), 1,1-diethoxycarbonyl-ethylene-2,2-dithiolate (dedt) (3), 1-ethoxycarbonyl-1-cyano-ethylene-2, 2-dithiolate (ecdt) (4), and 1,1-dicyano-ethylene-2,2-dithiolate (dcdt) (5), were prepared from cis-dichlorobis[1-(9-anthracene)phosphirane]platinum(II) (1). Complexes 3 and 5 were characterized by X-ray crystallography and were found to have vastly different crystal and molecular structures. The crystal and molecular structure of 3 is dominated by intramolecular pi-stacking between the anthracene rings of the cis-bis(anthracene)phosphiranes with a ring...ring separation of 3.48(6) A. The molecular structure of 5 does not exhibit an intramolecular interaction between the anthracene rings. Instead, the crystal structure of 5shows significant intermolecular pi-stacking between the anthracene rings of the phosphirane ligands of adjacent molecules packed in the crystal lattice. The intermolecular stacking interaction results in a ring...ring separation of 3.33(4) A. Complexes 2-5 were found to emit at 530 nm at low temperatures in the solid state. Complex 5 emits strongly in fluid THF or benzene solution at 430 nm.     

Aza-analogues of cage compounds: Potential precursors to azacubanes and 1-azahomocubanes

Exploration of the reactions of the 9-azahomocubane system led to derivatives of two small-ring systems containing aza-bridging atoms, 5-azatetracyclo[4.2.0.0^3,8.0^4,7]octane and 9-azatetracyclo[4.3.0.0^2,5.0^4,7]nonane. The structures were characterized by X-ray diffraction analyses. There are no prior X-ray structural reports on these systems.     

Diffusion coefficients of the monomer and oligomers in hydroxyethyl methacrylate

The diffusion coefficients are reported of rubbery ternary systems consisting of the polymer, its monomer analogue (i.e., the saturated equivalent of the monomer), and trace quantities of oligomers (dimer, trimer, tetramer and hexamer) for 2‐hydroxyethyl methacrylate (HEMA). These have been obtained with pulsed‐field‐gradient NMR spectroscopy with a polymer weight fraction (f_p) of 0 ≤ f_p ≤ 0.4. The oligomers are macromonomers synthesized with a cobalt catalytic chain‐transfer agent. The diffusion coefficients are about an order of magnitude smaller than those for monomers such as methyl methacrylate; this effect is ascribed to hydrogen bonding in HEMA. The diffusion coefficient D_i of an i‐meric oligomer has been fitted with moderate accuracy by an empirical universal scaling relation, D_i(f_p)/D₁(f_p) ≈ i, previously found to provide an adequate fit to corresponding data for styrene and for methyl and butyl methacrylates. The approximate empirical scaling relation seems to hold for a remarkably wide range of types of monomer/polymer systems. These results are of use in modeling rates and molecular weight distributions in free‐radical polymerization, particularly for termination (which is chain‐length‐dependent and is controlled by the diffusion coefficient of chains of the low degrees of polymerization studied here). © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2491–2501, 2003