Incorporation of Sulfur Dioxide into the Products of Reaction of Schiff Bases with Halo- or Alkylthio-ketenes in Liquid SO2. Preliminary communication

A simple ‘three-component-reaction’ between halo- or alkylthio-ketenes, Schiff bases and sulfur dioxide, yielding 4-oxo-1,3-thiazolidine-1,1-dioxides 4 in one step, is presented.     

Structural and Molecular Basis of the Catalytic Mechanism of Geranyl Pyrophosphate C6-Methyltransferase: Creation of an Unprecedented Farnesyl Pyrophosphate C6-Methyltransferase

Prenyl pyrophosphate methyltransferases enhance the structural diversity of terpenoids. However, the molecular basis of their catalytic mechanisms is poorly understood. In this study, using multiple strategies, we characterized a geranyl pyrophosphate (GPP) C6-methyltransferase, BezA. Biochemical analysis revealed that BezA requires Mg²⁺ and solely methylates GPP. The crystal structures of BezA and its complex with S-adenosyl homocysteine were solved at 2.10 and 2.56 Å, respectively. Further analyses using site-directed mutagenesis, molecular docking, molecular dynamics simulations, and quantum mechanics/molecular mechanics calculations revealed the molecular basis of the methylation reaction. Importantly, the function of E170 as a catalytic base to complete the methylation reaction was established. We also succeeded in switching the substrate specificity by introducing a W210A substitution, resulting in an unprecedented farnesyl pyrophosphate C6-methyltransferase.     

The Electrocyclic Cyclopropyl-Allyl Rearrangement. Preliminary communication

MINDO-2 SCF calculations indicate that ring-opening of cyclopropyl radical (I) to allyl radical (II) is more favourable via a disrotatory reaction path, the calculated activation energy being ～30 kcal/mole. (For conrotatory opening the activation energy was found to be ～44 kcal/mole.) The two critical motions of the nuclei during the transformation are found to be strongly decoupled, i.e. rupture of the CH₂βCH₂ bond precedes rotation of the CH₂ groups. As predicted by qualitative theories both ring-opening modes are unfavourable since they involve a change in electronic ground-state symmetry between I and II. The preferred ring-opening mode is discussed qualitatively in terms of Evans' principle.     

The Adamantane Rearrangement of 1,2endo-Trimethylenenorbornane. Preliminary communication

1,2endo-Trimethylenenorbornane (1) in the presence of aluminium bromide in carbon disulfide at ?60° isomerizes at a much higher rate than its 2exo-isomer 2 to 2endo, 6endo-trimethylenenorbornane (3) as the sole product. By consequence, the hydrocarbon 2 being the next intermediate in the sequence of the adamantane rearrangement of 1 seems to be very unlikely.     

Photoactive Analogs of Farnesyl Pyrophosphate Containing Benzoylbenzoate Esters: Synthesis and Application to Photoaffinity Labeling of Yeast Protein Farnesyltransferase

Farnesyl pyrophosphate (FPP) is involved in a large number of cellular processes including the prenylation of transforming mutants of Ras proteins implicated in cancer. Photoactive analogs could provide useful information about enzyme active sites that bind farnesyl pyrophosphate; however, the availability of such compounds is extremely limited. Molecules that incorporate benzophenone moieties are attractive photoaffinity labeling reagents because of their useful photochemical properties. Here, the syntheses of two compounds, 3a and 3b, containing para- and meta-substituted benzoylbenzoates are described. Compounds 3a and 3b are competitive inhibitors (with respect to FPP) of yeast protein farnesyltransferase (PFTase) with K(i) values of 910 and 380 nM, respectively. Both compounds inactivate PFTase upon photolysis, resulting in as much as 44% inactivation of enzyme activity. Photolysis of PFTase in the presence of [(32)P]3a or of [(32)P]3b results in preferential labeling of the beta subunit, suggesting that this subunit is involved in prenyl group recognition. These compounds should be valuable tools for studying enzymes that utilize FPP as a substrate.     

Twista-4,9-diene. Preliminary communication

A synthesis of twista-4,9-diene ( 17 ) from tricyclo[4.3.1.0^3,8]dec-4-en-10-one ( 2 ) is described.     

Light-induced dehydrodimerization of pyrroles. Preliminary communication

Irradiation (λ>280 nm) of 3-hydroxypyrroles 1 in acetonitrile leads to the formation of 3,3′-bi-3H-pyrroles 2 in reasonable to good yields.     

The Radical Cation of Cyclobutene and its Photoproduct. Preliminary communication

The hitherto unknown radical cation of cyclobutene ( 2 ) has been generated in a CFCl₃ matrix by γ rays at 77 K. The coupling constants, as determined from the ESR spectrum of 2 ⁺, are 2.80 and 1.11 mT for the four CH₂ and the two CH = protons, respectively. Photo-induced ring opening of 2 ⁺ yields a radical cation which exhibits the same ESR and ENDOR spectra as those observed upon direct ionization of s-trans-buta-1, 3-diene (s-trans -1 ). The radical cation s-trans -1 ⁺, should, therefore, be the final product of this conversion.     

Incorporation of chlorine into hydroxy-apatite

Ca₅OH(PO₄)₃ and Ca₅Cl(PO₄)₃ readily form solid solutions Ca₅(OH_1−xCl_x)(PO₄)₃, if synthesized at 1000°C under p_H2O = 4 Torr from CaHPO₄, Ca(CH₃COOH)₂ and CaCl₂. The crystallographic a-axis expands from 9.418 to 9.634 Å, the c- axis contracts from 6.884 to 6.778 Å with increasing Cl content. A new OH stretching band appears in the IR spectrum at 3496 cm⁻¹ for x < 0.5. Two new OH bending bands appear at 755 and 795 cm⁻¹ for x > 0.5. By comparison with the corresponding IR bands in the hydroxy-fluoroapatite solid solution it is to be concluded that the OH…Cl hydrogen bond is stronger than the OH…F bond. This anomalous behavior reflects the difficulty encountered when Cl⁻ substitutes for OH⁻ in the (OH, Cl)-apatite. The large Cl⁻ prefers the halfway position between the Ca-triangles (as in pure Cl-apatite) whereas the OH⁻ sits slightly above or below the plane of the three Ca²⁺ (as in pure OH-apatite). Geometrically this is unfavorable leading to the a-axis contraction and to the OH…Cl compression. The seemingly strong hydrogen bond found in (OH, Cl)-apatite solid solutions destabilizes the structure and explains why, under biological conditions, the OH-apatite discriminates against Cl⁻.     

Development of Petri Net-Based Dynamic Model for Improved Production of Farnesyl Pyrophosphate by Integrating Mevalonate and Methylerythritol Phosphate Pathways in Yeast

In this case study, we designed a farnesyl pyrophosphate (FPP) biosynthetic network using hybrid functional Petri net with extension (HFPNe) which is derived from traditional Petri net theory and allows easy modeling with graphical approach of various types of entities in the networks together. Our main objective is to improve the production of FPP in yeast, which is further converted to amorphadiene (AD), a precursor of artemisinin (antimalarial drug). Natively, mevalonate (MEV) pathway is present in yeast. Methyl erythritol phosphate pathways (MEP) are present only in higher plant plastids and eubacteria, but not present in yeast. IPP and DAMP are common isomeric intermediate in these two pathways, which immediately yields FPP. By integrating these two pathways in yeast, we augmented the FPP synthesis approximately two folds higher (431.16 U/pt) than in MEV pathway alone (259.91 U/pt) by using HFPNe technique. Further enhanced FPP levels converted to AD by amorphadiene synthase gene yielding 436.5 U/pt of AD which approximately two folds higher compared to the AD (258.5 U/pt) synthesized by MEV pathway exclusively. Simulation and validation processes performed using these models are reliable with identified biological information and data.     

A Photo-initiated Wagner-Meerwein Rearrangement. Preliminary communication

Irradiation of the octalin-derived sesquiterpene oxide α-agarofuran in methanol leads to rearrangement to the perhydroazulene system, in addition to simple double-bond migration to β-agarofuran. This rearrangement apparently proceeds through a carbonium-ion-like intermediate, whereas conventional generation of a carbocation leads only to opening of the oxide ring without rearrangement.     

Hydride Abstraction from Benzocyclopropene. Preliminary communication

The reaction between benzocyclopropene ( 1 ) and triphenylmethyl fluoroborate in acetonitrile shows an isotope effect of 6.7 and the isolation of the resulting triphenylmethane and benzaldehyde has been effected. A mechanism for the formation of the latter is proposed, involving an intermediate benzocyclopropenium ion ( 2 ).     

Dendrophanes: Water-Soluble Dendritic Receptors. Preliminary communication

The dendritic cyclophanes (dendrophanes ) 1–3 containing a [6.1.6.1]paracyclophane as the initiator core embedded in dendritic poly(ether-amide) shells of first ( 1 ), second ( 2 ), and third ( 3 ) generation were prepared and characterized. The X-ray crystal-structure analyses of esters 7 and 4 , derivatives of cyclophane core 9 and first-generation dendrophane 1 , respectively, displayed open cavity binding sites suitable for the inclusion complexation of aromatic substrates. With their carboxylate surface groups, dendrophanes 1–3 were readily soluble in aqueous phosphate buffer (pH 8.0), and the complexation of naphthalene derivatives was investigated by ¹H-NMR and fluorescence titrations. The binding studies demonstrated that the cyclophane cavity remains open and accessible to appropriate substrates even at higher dendritic generations. The 1:1 complexes formed in aqueous buffer were of similar stability to those formed by the unbranched core 9 (K_a between 1000 and 10000 1 mol^?1, 300 K). Investigations with the fluorescent probe 6-(p-toluidino)naphthalene-2-sulfonate ( 12 ) showed that the micropolarity at the dendrophane core decreases with increasing generation number.     

The Reaction of Pyruvic Acid with Amines and Aminoesters Reexamined. Preliminary communication

Phenylglycine esters react with pyruvic acid to give α-methylsuccinic amides 9 instead of the expected Schiff bases 8 , analogously to p-anisidine but unlike aniline.