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The selective tritiation of the methylene carbon atom of the carcinogens, N-fluoren-3-yl-and N-fluoren-1-ylacetohydroxamic acid, has been investigated. The synthesis of N-[9-3H]fluoren-3-ylacetohhydroxamic acid involves hydrogenolysis of 3-aminofluoren-9-one to [9-3]fluoren-3-amine with LiAl3H4-A1C1-. The tritiated amine is oxidized to 3-nitro-[9-3H]fluorene with m-chloroperoxybenzoic and the labeled nitro compound is partially hydrogenated to the 3H-hydroxamic acid with 10% Pd–C catalyst in presence of acetic anhydride and triethylamine or dimethylaniline. N-[9-3H]fluoren-1-ylacetohydroxamic acid may be obtained from 1-aminofluoren-9-one by the same procedure. However, N-[9-3H]fluoren-2-ylacetohydroxamic acid cannot be prepared in this way because reduction of 2-aminofluoren-9-one with LiA1H4-A1C13 does not proceed beyond the alcohol, 2-aminofluoren-9-ol.

A selective and quantitative method was developed for a microscale preparation of 4-thiouracil-2-14C by the direct thiation of uracil-2-14C. From pyridine, dioxane, and tetralin as the thiation solvents, the best yield was obtained in dioxane (96.6% of 4-thiouracil-2-14C). The simultaneous labelling with 14C + 35S was obtained by isotope exchange with elemental sulfur-35S on refluxing in dimethylformamide. The present procedure may be used as a general method for the preparation of 14C or 14C + 35S labelled bases of nucleic acids of both the pyrimidine and purine type as well as the corresponding nucleosides and nucleotides.

Interest in labeled compounds which can be studied as brain metabolites and can be detected in vivo has led to production of carbon-11 labeled acetoacetic acid (1-11C-acetoacetic acid). This synthesis, which was designed specifically for use with short-lived isotopes, utilizes a solution of the stable enolate anion of acetone, generated by the reaction of CH3Li and isopropenyl acetate, to which the 11CO2 is added to produce the labeled acetoacetic acid in ∼55% yield with a synthesis time of only 40 minutes from the end of bombardment.

Catalytic reductive dehalogenation of 5-bromo-6-azauracil with carrier-free tritium led to 6-azauracil-5-3 H of a molar activity of 19.0 Ci/mmole. The reaction conditions for the catalytic reductive dehalogenation were examined in tracer experiments. Microbial transformation was used for the preparation of 6-azauridine-5-3 H from 6-azauracil-5-3 H. 6-Azauridine-5-3- H was prepared at a molar activity of 18.8 Ci/mmole. In both compounds the stability of tritium was investigated in an aqueous medium at 100°C.

Analogs of adenosine-3′,5′-cyclic phosphate (cAMP) modified in positions 2 (Cl, Br, SCH 3 ) and 2′ (2,4-dinitrophenyl) and doubly modified in positions 1 and 2 (N 1 O and Cl), 2 and 2′ (Cl and 2,4-dinitrophenyl), have been synthesized by convenient methods. These derivatives have been examined as alternative activators of cAMP-dependent protein kinase isolated from bovine muscle and as alternative substrates for a cyclic phosphodiesterase from bovine heart. All analogs activated the kinase, most of them being more effective than cAMP. All were degraded by the diesterase, several at lower rates.

Starting from 3, 4-dimethylfluorene the title compound, 5, 6-dimethyl-7, 12-dihydro-indeno[1,2-a]fluorene (IV), is synthesized in four steps (overall yield 9%). The same hydrocarbon is also obtained in four steps starting from the phthalaconecarboxylic acid of Gabriel. This corroborates the structure of IV.

The 1 B 2u -band CD of siccanin ( 3 ) and some of its derivatives obeys the known rules for the benzene chromophore with the appropriate substitution pattern. The CD spectrum of the chromanone 8 is better resolved than that of related flavanones, the band between 300–320 nm is most probably the 1 B 2u -band of this chromophore. The non-planar styrenes 10–12 symmetrically substituted in the benzene ring with respect to the “pivot” bond follow Crabbe's rule, and the absolute configuration of siccanochromene-A ( 13 ) in the chromene ring follows from its CD to be S .

Six alkaloids have been isolated from the fruits of the plant Daphniphyllaceae . Two of them are new alkaloids, namely methyl homodaphniphyllate ( 1 ) and daphnilactone-B ( 2 ). The structure of the former was deduced by chemical transformation from daphniphylline ( 3 ). The structure of daphnilactone-B was estimated by the exhaustive spectral analysis as well as by chemical evidences, and finally determined by an X-ray crystallographic analysis of the free base.

5-Cyclooctenylbromid (I) reagiert mit Dimethyllithiumcuprat (II) zu den Bicyclo= (3,3,0)octanen (IIIa) und (IIIb) und nur zu 23% zum Methyl-cycloocten (IV).

The systematic analysis of solid phase peptide synthesis by Edman degradation becomes possible by the development of a technique (high pressure liquid chromatography) for the determination of phenylthiohydantoins in trace amounts. By its qualitative beside the quantitative results the degradation method offers the possibility to follow formation and propagation of failure sequences over more than one synthetic cycle. Scope and limitations of the method are discussed.

Epoxyzucker mit freien Hydroxylgruppen konnen unter Verwendung von Rutheniumoxid und Natriumperjodat zu den Epoxyketosen ohne Angriff auf die Epoxy- Gruppe oxidiert werden.

In a new approach to the specific labelling of organic compounds with tritium use is made of isotope exchange with tritium of certain specific hydrogen atoms in organic molecules when stirred with tritium gas in solution at room temperature in the presence of a metal hydrogen transfer catalyst. Specifically labelled tritiated compounds of high specific activity and radio-chemical purity are obtained. The method can be used for labelling a wide variety of organic compounds including purines, purine nucleosides and nucleotides, aromatic amines and amino acids, carbohydrates and steroids. Numerous examples are cited and possible mechanisms discussed.

Aus den Blattem von Cordyline cannifolia und C.Stricta wurde ein neues Sapogenindiol, das Cordylagenin (I) isoliert und identifiziert.

A PMR study of ten poly-(2,4-dinitrophenoxy)benzenes and naphthalenes together with appropriate reference compounds, showed that (1) relatively long-range anisotropic effects are observed; (2) these are roughly additive when several benzene rings are present; (3) in the absence of steric effects there is no preference between syn and anti dispositions of substituting rings about the central ring; (4) concerted libration and concerted rotation occur freely even in highly substituted diaryl ethers; and (5) a twist conformation is preferred about the individual ether links.

The protonation and deprotonation rates of the coordinated amide groups in the Ni2+ and Cu2+ complexes of 3,7-diazanonanediamide (DANA) and in the Cu2+ complex of 3,7-diazanonane-N,N′-diethylamide (DANEA) have been studied by stopped-flow techniques. For the interconversion M(H−2L) ⇌ ML, two consecutive reactions are observed in the case of Cu2+ with DANA or DANEA, whereas there is only one reaction for Ni2+ with DANA. Cu(H−2DANEA) is unusually labile, indicating a strong interaction between the N-ethyl groups. The conversion of the O- into the N-coordinated amide groups in NiDANA2+ is 25 times slower than in CuDANA2+. In the case of Ni2+ this excludes a step with water substitution, which is involved in one of the reaction paths observed for the Cu2+ complexes, since the rates of water exchange differ by a factor of 105 for the two metal ions.

A controlled clinical trial was carried out in which three drug regimens, rifampicin plus isoniazid, rifampicin plus PAS, and isoniazid plus PAS, administered for 6 months, were compared in patients with newly diagnosed pulmonary tuberculosis. The drugs were given in the following doses: rifampicin, 450 mg up to 60 kg and 600 mg over 60 kg body weight in one dose; isoniazid, 5 mg/kg in one dose; PAS, 10 g up to 60 kg and 12 g over 60 kg body weight, divided in two doses. Bacteriological results showed that all the treatment regimens had a similar efficacy. In the groups of patients who were administered rifampicin, faster disappearance of tubercle bacilli from sputum was observed. The roentgenographic changes were comparable in all groups. According to the results obtained, rifampicin is a drug whose effectiveness and tolerability are comparable with those of isoniazid.

Das naturliche Vorkommen des Reticulins (I) im Lerchensporn Corydalis cava (Papaveraceae) wurde sowohl durch Isolierung des Morphinandienons Sinoacutin (V) als auch durch Nachweis radioaktiv markierten Reticulins nach Futterungsversuchen mit markierten Aminosauren bewiesen, Damit ist in Erganzung zu fruheren Versuchen Reticulin als Biosynthesevorstufe der Aporphin-Alkaloide festgestellt. Detection of Reticuline as Precursor in Corydalis cava The natural presence of reticuline (I) in the larkspur Corydalis cava (Papaveraceae) was demonstrated by the isolation of the morphinanedienone-type alkaloid sinoacutine (V). Furthermore, after feeding experiments with labelled amino acids, labelled reticuline was detected in the plant. These results, combined with previous feeding experiments, provide strong evidence that reticuline is the precursor of aporphine alkaloids.

The methyl esters of the uronic acids derived from uridine, 5-fluorodeoxyuridine, 6-aza-2′-deoxyuridine and 2′,3′-o-isopropylideneadenosine were converted to the amides with aqueous d0·88 ammonia. After protection of the sugar hydroxyls each 5′-carboxamide was dehydrated with phosphoryl chloride at −5° to yield, after deprotection, the respective novel 5′-nitrile nucleosides. Treatment of the protected 5′-nitrile nucleosides with ammonium azide in DMF gave, after deprotection, the novel 5′-C-tetrazole nucleosides.

Homo-p-chinon (4 = Bicyclo[4.1.0]hept-3-en-2,5-dion) wurde hergestellt und auf seine Spektraleigenschaften untersucht. Die UV.-, IR.- und NMR.-Spektren sind charakteristisch fur die darin enthaltene Endion-und cis-disubstituierte Cyclopropan-Substruktur, ohne eine starke Wechselwirkung zwischen den beiden zum Ausdruck zu bringen. Basische Thermolyse des Bis-p-toluolsulfonylhydrazons (9) von Homo-p-chinon ergab das bekannte 1,7 a-Diaza-inden (10). Dies bestatigt den fruher postulierten Mechanismus der Bamford-Stevens-Reaktion mit den zwei isomeren Bis-homo-p-chinonen (1a und 2a).

A number of 1-allylthio and 1-crotylthio 1-aminoalkenes derived from ketones and active methylene compounds has been prepared and rearranged to the corresponding thioamides (thio-Claisen rearrangement). Besides rearrangement products, small amounts of 1-alkyl-thio-N-alkyl-N-phenyl-1-aminoalkenes have also been isolated. When the ketene derivatives did possess a H-atom on nitrogen, cleavage of the formed thioamide produced phenyl isothiocyanate and substituted active methylene compounds.