Sequential claisen and cope rearrangement for formation of 3-(-1-methylethyl)-substituted α,β-unsaturated aldehydes

3-(1-Methylethyl)-7-methyl2,6-octadienal, was prepared from 1,1,3-triethoxy-3,4-dimethylpentane and 3-methyl-2-buten-l-ol in a one-pot procedure utilising Claisen and Cope rearrangement of an intermediate dienol-allyl ether.     

Structures cristallines et moléculaires des muscs macrocycliques III. La muscone et sa 2,4-dinitrophénylhydrazone

Crystal and Molecular Structure of Macrocyclic Musks. III. Muscone and its 2, 4-Diuitrophenylhydrazone Muscone (3-methylcyclopentadecanone C₁₆H₃₀O) forms orthorhombic plastic-crystals with Z = 2 (a = 5.560(4), b = 8.176(6), c = 17,168(20) Å). Single crystals are obtained by zone melting at 258 °K. The high degree of disorder and the ambiguity of space group have precluded a structural determination by X-ray diffraction methods. The crystal structure of muscone 2,4-dinitrophenylhydrazone (DNPHM; C₂₂H₃₄N₄O₄, triclinic, space group P¯, a = 8.015 (4), b = 8.235 (2), c = 17.409 (4) Å. α = 102.69 (4), β; = 93.86 (3), γ = 96.03 (3)° Z = 2) was solved by direct methods and refined to a final R of 0.155 (R_ω = 0.102). The macrocycle shows static disorder, which could be partially resolved by analysis of the anisotropy of the atomic vibrational parameters. Eight possible conformers with reasonable geometries emerged from the subsequent refinements and were used as starting models in force-field calculations, which converged to four quinquangular conformations ([25233]; [34233]; [21423*4]; [3423*4]) with similar energies. In the molecular packing, the interactions between macrocycles and substituents are minimized. They are comparable to those described for the cis- and trans-civetone DNPH derivatives [1] [2].     

Approaches to charge calculations in molecular mechanics

Alternative methods of estimating atomic charges in haloalkanes are presented, derived from quantum mechanical and classical treatments. A scheme based on a breakdown of the transmission of charge by polar atoms into one-bond, two-bond, and three-bond additive contributions is given, in which the one-bond effect is proportional to the difference in the electronegativities of the bonded atoms, and the two- and three-bond effects functions of the atomic electronegativity and polarizability. Suitable developments of the basic scheme, including an iterative self-consistent process, give calculated dipole moments for a variety of haloalkanes in good agreement with the observed values. The atomic charges obtained by this scheme are compared with other estimates of these charges. They are similar to those derived from a simple LCAO –MO scheme but differ from those obtained by population analysis of more refined quantum mechanical calculations.     

Quantum chemistry with an attached processor

The Floating Point Systems, Inc. Model 164 Attached Processor (FPS-164) is a high-speed, pipelined, parallel processor designed for large-scale scientific computation. Benchmark studies of operations common in quantum chemistry codes are discussed and the performance of the FPS-164 is compared with other commonly available computers. A complete system of electronic structure codes has been implemented on the FPS-164 using the Fortran-77 cross-compiler and calls to optimized vector and matrix routines. The conversion of a generalized valence bond (GVB ) code illustrates the strategy adopted to adapt Fortran codes to the FPS-164. A typical production example, a large scale (GVB ) and configuration interaction calculation on the vinyl radical, shows a net throughput equivalent to nearly nine VAX 11/780 computers.     

Photochemical and Photophysical Studies of 3-Amino-6-lodoacridine and the Inactivation of λ Phage

Abstract— The photochemistry and photophysics of 3-amino-6-io-doacridine (Acr-I) was studied. Photolysis (350 nm) of Acr-I (free base) generates products consistent with a free radical intermediate in methanol, benzene and carbon tetrachloride. The Acr-I hydrochloride is shown to bind to calf thymus DNA and to the self-complementary dinucleotide cytidylyl-(3′-5′)-guanosine (CpG) minidu-plex in a manner similar to that of proflavine (Acr-NH₂), a known DNA intercalator. The Acr-I is shown to more efficiently nick supercoiled plasmid DNA pBR322 upon 350 nm or 420 nm photolysis than Acr-NH₂. The efficiency of Acr-I-sensitized DNA nicking is not oxygen dependent. Photolysis of the Acr-I/(CpG)₂ complex leads to cleavage of the dinucleotide and to cytidine base release by selective damage to a specific ribose moiety. Dinucleotide cleavage occurs equally well in the presence or absence of oxygen, thereby eliminating a singlet oxygen- or peroxyl radical-mediated process. Photolysis of Acr-I in the presence of a mononucleotide (GMP) or a non-self-complementary dinucleotide (uridylyl-[3′-5′]-cytidine– UpC) does not lead to fragmentation and base release. Similarly, photolysis of the Acr-NH₂/(CpG)₂ complex does not lead to fragmentation and base release. The data indicate that photolysis of an iodinated intercalator bound to CpG or plasmid DNA generates an intercalated aryl radical and that the reactive intermediate initiates a sequence of reactions that efficiently nick nucleic acids. The inactivation of Λ phage sensitized by Acr-I with UV (350 nm) light is oxygen independent but with visible (420 nm) light is strongly oxygen dependent. The Acr-I fluoresces more intensely when excited at 446 than at 376 nm. Thus, UV photolysis may lead to C-I bond homolysis and free radical formation, a process that is not energetically feasible with visible light. The results demonstrate the difficulty of extrapolating model studies involving simple molecules and DNA to understanding the mechanism of viral inactivation with a particular sensitizer.     

The synthesis of phenanthrodibenzothiophenes

The synthesis of phenanthro[1,2-c]dibenzothiophene (6) , phenanthro[4,3-c]dibenzothiophene (10) , phenanthro[2,1-a]dibenzothiophene (14) , phenanthro[3,4-a]dibenzothiophene (16) , phenanthro[1,2-a]dibenzothiophene (19) , phenanthro[2,1-b]dibenzothiophene (20) , 8-methylphenanthro[3,2-a]dibenzothiophene (24) , 7-methylphenanthro[1,2-a]dibenzothiophene (25) , phenanthro[3,4-a]dibenzothiophene (27) , phenanthro[4,3-a]-dibenzothiophene (28) , 6-methylphenanthro[2,3-a]dibenzothiophene (31) , and 5-methylphenanthro[4,3-a]dibenzothiophene (32) is described.     

Structural isomerism of mono- and sesquiterpenoid skeletons

A generator of chemical structures (CONGEN) has been utilized to investigate two aspects of the structural isomerism of mono- and sesquiterpenoid skeletons: (1) the scope of possible isomers under various structural constraints; and (2) the scope of possible isomers based on a mechanistic model which allows interactive exploration of reactions of formation and interconversion. The possibilities, even under severe constraints, are many more than the structural types commonly encountered in natural. These results indicate the potential danger of structural assignment based in part on biogenic grounds.     

Photobinding of ketoprofen in vitro and ex vivo

Ketoprofen (KP), a non-steroidal anti-inflammatory drug of the 2-aryl propionic class, has been shown to produce photoallergic side effects as well as cutaneous photosensitizing properties that induce other phototoxic effects. In the present study we investigated photobinding of ketoprofen to both human serum albumin (HSA), a model protein, and to ex vivo pig skin and its photodegradation. Results demonstrate that photoadduct formation and photodegradation progressively increased with irradiation time where they reach a maximum. Maximum photobinding to the viable layer of the epidermis was about 7-8% of the initial radiolabelled KP added, in the region of 15-30 min UV irradiation. These results were comparable to in vitro results that were seen with photobinding of KP to HSA; in this case, the quantity of covalently bound material was approximately 10% of the initial, after a maximum of 18 min irradiation. It was found by HPLC analysis that the KP decrease is accompanied by an increase of the corresponding photoproduct, decarboxylated ketoprofen (DKP). The yield of DKP reaches a maximum at around 15 min. DKP appears to play an important role in vitro and ex vivo, being the major photoproduct and responsible for the photobinding process. Using micro-autoradiographical techniques we investigated the penetration and distribution of ketoprofen in ex vivo pig skin in greater detail. It was apparent that percutaneous absorption was taking place and that most of the ketoprofen was predominately localised in fibroblasts in the papillary dermis. No other specific localisation within the skin architecture was identified. Although there were differences in the quantities of bound ketoprofen within the different layers of the skin, these levels did not appear to correlate with irradiation time.     

Efficient synthesis of various acycloalkenyl derivatives of pyrimidine using cross-metathesis and Pd(0) methodologies

Novel acyclonucleosides (9a-d, 10a-d, 18a,b and 19a,b) have been prepared using Pd(0) and cross-metathesis methodologies. The allylic N-alkylation under Tsuji-Trost conditions was used to introduce the nucleobase, while the Suzuki-Miyaura reaction afforded C-5 substituted uracil analogues. The cross-metathesis performed with a ruthenium catalyst was used to provide new acycloalkenyl nucleosides. The antiviral activities of all final compounds have been evaluated.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 14. 14-methylbenzo[h]naphtho-[1′2′:4,5]thieno[2,3-c][1,6]naphthyridine

Benzo[h]naphtho[1′2′:4,5]thieno[2,3-c][1,6]naphthyridine, a novel polycyclic heterocyclic ring system, has been synthesized as the 14-methyl derivative 8 in four steps from known intermediates. The structure of 8 is supported by assignment of the proton and the protonated carbon atoms by 2D-nmr techniques (COSY and a carbon-hydrogen one-bond coupling experiment).