Fritz Sauter

A bicentennial of betulin

Abstract The literature on the history, identification, determination, isolation and distribution in plants of betulin as well as its technological applications and its pharmacology is reviewed and the chemotaxonomy of the angiosperms in relation to betulin is discussed.

NEW HETERO-ANNELATION REACTIONS USING N-BIS-(METHYLTHIO)-METHYLENE-AMINO AND RELATED REAGENTS

SummaryReaction of acyclic (B1–3) and cyclic (R4–5)BMMA (=N-[bis-(methylthio)-methylene]-amino) reagents withGewald-type thiophene derivatives (2,3) led to annelation of pyrimidine moieties. Thus, linear thiazolo- or thiazino- and pyrrolo-, pyrido- or azepino-fused thiopyrano[4′,3′:4,5]thieno-[2,3-d]pyrimidines (5 and6) as well as the angular imidazo-fused thiopyrano[4′,3′:4,5]thieno-[2,3-d]pyrimidine8 were easily obtained from one-pot reactions in good yields.ZusammenfassungUmsetzung von acyclischen (R1–3) und cyclischen (R4–5)BMMA-Reagenzien (BMMA=N-[bis-(Methylthio)-methylen]-amino)mitGewald-artigen Thiophenderivaten (2,3) führte zur Anellierung von Pyrimidinringen. Auf diese Weise konnten linear kondensierte Thiazolo- oder Thiazino- und Pyrrolo-, Pyrido- oder Azepinothiopyrano[4′,3′:4,5]thieno[2,3-d]pyrimidine (5 und6) sowie das angulär imidazo-anellierte Thiopyrano[4′,3′:4,5]thieno[2,3-d]pyrimidin8 in guten Ausbeuten auf direkte Weise in Eintopfreaktionen erhalten werden.

Cycloadditions of nitrile oxides and nitrones to 4,4-methylene-1-methylpiperidine: Studies in regio- and stereoselectivity

SummaryA series of spiro-substituted isoxazole derivatives were synthesized by 1,3-dipolar cycloadditions of nitrile oxides and nitrones to 4,4-methylene-1-methylpiperidine. Since nmr studies confirmed that only one regioisomer was formed selectively, semi-empirical quantum mechanical methods (AM1) were used to rationalize this regiochemical preference via calculation and inspection of HOMO-LUMO-energy and coefficients. X-ray structure analysis carried out for one of these products showed the occurrence of only one stereoisomer, explicable by comparing AM1-calculated ΔHf-values of all possible cycloadducts.ZusammenfassungEine Reihe von spiro-substituierten Isoxazolderivaten wurden durch 1,3-dipolare Cycloaddition von Nitriloxiden und Nitronen an 4,4-Methylen-1-methylpiperidin erhalten. Da NMR-Studien ergaben, daß dabei nur eine der beiden denkbaren regioisomeren Strukturen entsteht, wurde versucht, diese regiochemische Preferenz durch Berechnung und Vergleich von aus halb-empirischen quantenmechanischen Methoden (AM1) ermittelten HOMO-LUMO-Energien und Koeffizienten zu erklären. Zusätzlich wurde an einem dieser Produkte dessen Stereochemie mittels Röntgenstrukturanalyse als einheitlich festgestellt, interpretierbar durch Vergleich der AM1-ermittelten ΔHf-Werte der in Frage kommenden Cycloaddukte.

Reagents for new heteroannelation reactions III. 2-(Methylthio)-2-thiazoline

SummaryA variety of partly novel tri- and tetracyclic hetero systems were obtained by reaction of heteroaromatic 2-aminoesters with 2-(methylthio)-2-thiazoline, yielding double-annelation of a thiazolo[2,3-b]pyrimido moiety in a one-pot process.ZusammenfassungEine Reihe z.T. neuer tri- und tetracyclischer Heterosysteme wurde durch Reaktion von heteroaromatischen 2-Aminoestern mit 2-(Methylthio)-2-thiazolin erhalten, wobei im Eintopfverfahren durch doppelte Cyclisierung jeweils eine Thiazolo[2,3-b]pyrimido-Einheit anelliert wurde.

GC/MS and chemometrics in archaeometry

Summary100 mg amounts of glue on two copper-age arrowheads have been investigated by means of gas-chromatography/mass spectrometry and chemometrics. The samples have been identified as birch bark derivatives, but the distribution patterns of triterpenoids and steroids show significant differences to similar samples from younger archaeological periods that can be explained by the use of a different species of birch and a different method of preparation.

A Novel Synthesis of 3,3-(Spiro)substituted Azetidines

A smooth and efficient new synthesis for 3,3-disubstituted azetidines, starting from readily available nitriles, was established: α-hydroxymethylation of the starting materials, followed by O-tosylation and LiAlH 4 -reduction of the key intermediates thus obtained, led ― via spontaneous cyclization of the intermediate amino derivatives ― to 3,3disubstituted azetidines. Scope and limitations of this new method were studied with respect to generalized applicability: the target compounds were accessible in good yields for a variety of starting materials (cyclic and acyclic di(hetero)aryl, (hetero)arylalkyl, dialkyl, as well as basic moieties). The products thus obtained may be of interest for ensuing conversions due to their unblocked nitrogen

Synthesen neuer Chinolon-Chemotherapeutika, 1. Mitt.: Pyridochinoline und Pyridophenanthroline als “lin-benzo-Nalidixinsäure”-Derivate

Expansion of nalidixic acid (NA) has been accomplished by linear insertion of a benzo-ring between the two pyrido moieties. The resulting compounds exhibit antibacterial activity comparable toNA and are highly fluorescent. The regioselective hydrogenation of 1,7-phenanthrolines was studied.

Synthesis of spiro-substituted 1,3-oxazines by a new sequence leading to spiroheterocycles

SummaryThe target compounds, i.e. 1,3-oxazines which are spiro-substituted in position 6 by a piperidine moiety, are derived from 1-oxa-3,9-diaza-spiro[5.5]undecane, a novel heterocyclic parent system. They were all approached by the following three-step sequence: 1,3-dipolar cycloadditions of nitrile oxides and nitrones to piperidines bearing an exocyclic methylene group gave the corresponding spiro-substituted oxazole derivatives3. In a consecutive step these were cleaved by hydrogenolysis to γ-amino-alcohols4, which in a final step were recyclized by insertions of a C1-unit to yield the target structures5–10: thus ade facto ring-extension of spiro-oxazoles to spiro-oxazines was accomplished.ZusammenfassungDie Zielverbindungen, d.h. 1,3-Oxazine mit einem Piperidinring als Spiro-Substituenten in 6-Stellung, leiten sich von 1-Oxa-3,9-diaza-spiro[5.5]undecan, einem neuen heterocyclischen Grundkörper, ab. Sie wurden alle mit Hilfe der folgenden dreistufigen Synthesefolge zugänglich gemacht: 1,3-dipolare Cycloadditionen von Nitriloxiden und Nitronen an Piperidinderivate mit einer exocylischen Methylengruppe gaben die entsprechenden spiro-substituierten Oxazolderivate3. Diese wurden anschließend hydrogenolytisch zu den γ-Aminoalkoholen4 gespalten, welche schließlich wieder unter Einschub von einem C-Atom zu den Zielstrukturen5–10 cyclisiert wurden: dadurch wurde einede facto-Ringerweiterung von Spiro-Oxazolen zu Spiro-Oxazinen erreicht.

Synthese von 1H-[1]Benzothieno[3,2—c]pyrazol-Derivaten

Derivatives of 1H-[1]Benzothieno[3,2−c]pyrazole were synthesized by a new method: 1.3-dipolar cycloaddition of substituted benzo[b]thiophene-1.1-dioxides with C-methyl-N-phenyl and C,N-diaryl-nitrilimines, resp., gave the corresponding title compounds. The structure was proved by conversion to known compounds.

Cyclisierungsreaktionen zu Thiazolo[3,2—a]thieno[2,3-d]pyrimidinen

Cyclisation of 2-(β-oxo-alkylthio)-thieno[2.3-d]pyrimidin-4(3H)-ones gave separable mixtures of the title substances and their [2.3-b]-isomers. The structure of the two isomers were be proved by comparison with a linear product synthesized by an unambiguous method. Similar cyclisations were achieved by reactions of 2-mercapto-thieno[2.3-d]pyrimidin-4(3H)-ones with chloroacetone, 1.2-dibromoethane or 1.3-dibromopropane.