Mass spectrometry in structural and stereochemical problems. CCLVI—electron impact induced fragmentation of juvenile hormone analogs

Complete high resolution mass spectra of several analogs of the juvenile hormones have been analyzed with the aid of our recently developed INTSUM program and mass spectra of deuterated analogs. Representative compounds chosen for study included the biologically interesting (2E, 4E)-3,7,11-trimethyl-2,4-dodecadienoates (1,2), (2E,4E)-11-methoxy-3,7,-11-trimethyl-2,4-do-decadienoates (3,4) and three analogs (5-7) of the trans-trans-farnesoate skeleton. These compounds display characteristic fragmentations which can be used to detect the presence of the compounds in complex mixtures using mass fragmentography or aid in the structure elucidation of related compounds.     

Asymmetric synthesis of 2-alkyl-perhydroazepines from [5,3,0]-bicyclic lactams

The synthesis and utility of a novel class of [5,3,0]-bicyclic lactams are described. Produced by the cyclodehydration of (R)-phenylglycinol with omega-keto acids, lactams 4-6 were obtained as separable diastereomeric mixtures ( approximately 2:1) in low yields ( approximately 40%). Higher chemical yield (up to 61%) was realized via an alternate route involving ring closure metathesis of 2-allyl-N-acroyl oxazolidines, 8. Stereoselective reductions of the syn-bicyclic lactams, 4a and 5a, occurred with the use of alane or lithiumaluminum hydride, affording azepine alcohols, 11a and 15a, of the R configuration at the 2-position, in good to moderate yields (50-88%). High selectivity was also observed in the diisobutylaluminum hydride reduction of the epimeric anti lactams, 4b and 5b, affording azepine alcohols, 11b and 15b, of the S configuration at C-2. Hydrogenolytic cleavage of the N-benzyl moiety afforded chiral 2-substituted perhydroazepines, (R)- and (S)-12, in good yields and good enantiomeric excesses (84-94%).     

Synthesis and structural characterisation of [Au2Pt2(PPh3)4(CN-xylyl)4](PF6)2: A platinum—gold cluster with a flattened butterfly geometry

[Au₂Pt₂(PPh₃)₄(CN-xylyl)₄](PF₆)₂ (CN-xylyl = 2,6-dimethylphenylisocyanide) has been synthesised from [Pt(C₂H₄)(PPh₃)₂] and [Au(CN-xylyl)₂]⁺ in CH₂Cl₂ and in the presence of an excess of CN-xylyl. A single crystal X-ray diffraction study has demonstrated that the metal atoms define a flattened butterfly with the gold atoms occupying the higher connectivity sites and forming a short bond of length 2.590(2) Å. The platinum—gold distances lie in the range 2.710(2)–3.026(2) Å.     

Dual responsive chemosensors for anions: the combination of fluorescent PET (Photoinduced Electron Transfer) and colorimetric chemosensors in a single molecule

The design and synthesis of two novel fluorescent PET anion sensors is described, based on the principle of ‘fluorophore-spacer-(anion)receptor’. The sensors 1 and 2 employ simple diaromatic thioureas as anion receptors, and the fluorophore is a naphthalimide moiety that absorbs in the visible part of the spectrum and emits in the green. Upon recognition of anions such as F⁻ and AcO⁻ in DMSO, the fluorescence emission of 1 and 2 was ‘switched off’, with no significant changes in the UV-vis spectra. This recognition shows a 1:1 binding between the receptor and the anions. In the case of F⁻, further additions of the anion, gave rise to large changes in the UV-vis spectra, where the λ_max at 455 nm was shifted to 550 nm. These changes are thought to be due to the deprotonation of the 4-amino moiety of the naphthalimide fluorophore. This was in fact found to be the case, using simple naphthalimide derivatives such as 6. Sensors 1 and 2 can thus display dual sensing action; where at low concentrations, the fluorescence emission is quenched, and at higher concentrations the absorption spectra are modulated.     

Some novel heterocyclic systems derived from 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-α]benzimidazole and the corresponding diamine

The preparation of 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-a]benzimidazole from 1,4-diacetamido-2,3-dinitrobenzene is described. Reaction of this compound with 2,5-dimethoxytetrahydrofuran produces 2,3-dihydro-8-nitro-7-N-pyrrolo-1H-pyrrolo[1,2-a]benzimidazole, which can be cyclised to produce two new heterocyclic ring systems, 9,10-dihydro-8H-pyrrolo[1,2-a]pyrrolo(1′,2′:1,2]imidazo[5,4-f]quinoxaline and 9,10-dihydro-8H-pyrrolo[2,1-c]pyrrolo[1′,2′:1,2]imidazo[4,5-h][1,2,4]benzotriazine. The corresponding diamine, 7,8-diamino-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazole undergoes a variety of condensation reactions to produce several new heterocyclic systems, for example, with formic acid, 1,7,8,9-tetrahydroimidazo-[4,5-e]pyrrolo[2,1-6]benzimidazole is formed and with diacetyl, 9,10-dihydro-2,3-dimethyl-8H-pyrrolo-[1′,2′:1,2]imidazo[5,4-y]quinoxaline is obtained.     

PHOTOSENSITIZED CARCINOGEN DEGRADATION AND THE POSSIBLE ROLE OF SINGLET OXYGEN IN CARCINOGEN ACTIVATION

Abstract— Dye sensitized photo-oxidation of various chemical carcinogens including 2-acetylaminofluorene, benzo(a)pyrene, 9,10-dimethyl-1,2-benzanthracene and 4-nitroquinoline- N -oxide has been studied in the presence and absence of oxygen. Visible light from a filtered 150 W Xe arc was used for photolysis. and carcinogen destruction was monitored spectrophotometrically. The carcinogens were solubilized in aqueous solution within micelles of various lipid-like surfactants. Photosensitized destruction of carcinogens by several triplet sensitizers has been observed. Enhanced damage in the presence of oxygen is also found. These results are consistent with photochemical oxidative damage to carcinogens being produced in aerated solutions via the sensitizer triplet state, possibly involving singlet oxygen. These manifold reactions are catalysed by micelles which concentrate polycyclic hydrocarbons in the non-polar environment within the micelles where the exclusion of water probably increases reactive species lifetimes. This model photochemical system mimics the aerobic metabolic activation of chemical carcinogens, which in part is believed to be mediated by various forms of activated oxygen.     

L-Phenylalanine Cyclohexylamide: A simple and convenient auxiliary for the synthesis of optically pure α,α-disubstituted (R)- and (S)-amino acids

This work describes L -phenylalanine cyclohexylamide ( 5c ) as a simple, cheap, and powerful chiral auxiliary for the synthesis of a series of optically pure α,α-disubstituted (R)- and (S)-amino acids of type 1 , such as (R)- and (S)-2-methyl-phenylalanine ( 1a ), (R)- and (S)-2-methyl-2-phenylglycine ( 1b ), and (R)- and (S)-2-methylvaline ( 1c ; Scheme 3). These amino acids were efficiently transformed into the suitably protected and activated amino acid building blocks (R)- and (S)- 12b and (R)- and (S)- 12c (Scheme 4) which are ready for incorporation into peptides by solution or solid-phase techniques. Based on the crystal structures of 6b, 6c , and 7a belonging to the diastereoisomeric peptides series 6 and 7 , the absolute configurations of each member of the series were determined. β-Turn geometries of type II′ and I were observed for 6b and 7a , respectively, whereas 6c crystallized in an extended conformation. The impacts of side-chain variation on conformation and crystal packing of these triamides are discussed.     

Practical synthesis of 1-aryl-6-(hydroxymethyl)-2-ketopiperazines via a 6-exo amide-epoxide cyclization

[reaction: see text] Chiral 1-aryl-6-(hydroxymethyl)-2-ketopiperazines can be prepared via an operationally simple, 6-exo epoxide ring-opening cyclization to form the ketopiperazine C6-N1 bond in high yields and with excellent enantiomeric purity.     

Installation of a Shielded SIMS for the Analysis of Irradiated Nuclear Fuels

A CAMECA IMS 6F secondary ion mass spectrometer (SIMS) for the analysis of irradiated nuclear fuel has been installed in the Microbeam Analysis Laboratory of the Institute for Transuranium Elements (ITU). This device is specially equipped with heavy metal shielding to enable the safe examination of irradiated nuclear fuel samples with activities up to 75 GBq. At ITU the shielded SIMS will be used in conjunction with EPMA taking advantage of the complementary nature of the two techniques and will make important contributions to ongoing research programmes such as the safety of nuclear fuels, the partitioning and transmutation programme and the characterisation of spent fuels. The paper describes the shielded SIMS installation and presents a selection of results from the commissioning tests.     

An Efficient Synthesis of Optically Pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-ama) and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-aml)

An efficient synthesis of enantiomerically pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-Ama) 1a and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-Aml) 1b is described (Schemes 1 and 2). Resolution of the racemic amino acids was achieved using L -phenylalanine cyclohexylamide ( 2 ) as chiral auxiliary. The free amino acids 1a, b were converted to the N^α-Boc,N^γ-Z-protected derivatives 11a, b (Scheme 3) ready for incorporation into peptides. Based on the three crystal structures of the diastereoisomeric peptides 8a, 8b , and 9b , the absolute configurations in both series were determined. β-Turn type-I geometries were observed for structures 8b and 9b , whereas 8a crystallized in an extended backbone conformation.