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Isolation, structure determination, synthesis, and biochemistry of the low-molecular-weight compounds of the secretion of exocrine glands of termites are described, with an emphasis on pheromones and defensive compounds.

Practical EPC-syntheses of δ-substituted-β-keto δ-lactones, subunits of the cochleamycins and macquarimicins, are presented. In consequence Tietze's tandem reaction is employed to combine δ-allyl-β-keto δ-lactone with a hydrindene derivative, the second subunit of these acetogenic antibiotics. Model reactions for the final oxidative radical tandem cyclization reveal that the electrophilic radical cyclizes exclusively in exo - trig fashion. However, with the intended precursor of macquarimicin C allylic hydrogen abstraction thwarted the oxidative radical tandem cyclization.

A racemic as well as an EPC-synthesis of the cis-hydrindene subunit of the cochleamycins, physiologically active microbial secondary metabolites, are reported. The five stereogenic centres of this subunit are introduced in high stereoselectivity in a short sequence by intermolecular Diels–Alder reaction, stereoselective methylation and hydride reduction. Cyclisation via nucleophilic addition, acidic fragmentation, regioselective Shapiro reaction and inversion of a secondary alcohol are the further key steps of these syntheses.

The cis -decalin subunit of coloradocin is synthesized starting with an intermediate of our synthetic attempts towards nodusmicin. After transforming the additional functionalities of this tetracyclic β-diketal reductive cleavage with SmI 2 leads to a tricyclic diketone. Selective reduction is followed by acidic fragmentation to the desired cis -decalin derivative. The very mild conditions of this fragmentation led us to examine a synthetic variant that should allow easy connection with other subunits of the projected convergent synthesis of this antibiotic.

The highly substituted subunit 6 of our convergent synthesis of nodusmicin was prepared utilizing Evans' oxazolidinone protocol. Compound 6 was then adjoined to the decalin subunit 7 using Martin's olefination method. To improve on the formation of the hindered trisubstituted double bond, the following model reactions were devised: reductive coupling of ester and keto functionality of tricycle 16 led to the α-hydroxyketone, which was converted to the cyclic sulfate 19 via the diol. Sodium naphthalide then converted 19 to the olefins 20 .

Starting with the unsaturated 1,4-meso-diol 1 , the enantiomerically pure 4-silyloxy enone 6 is prepared in high yields via diastereomeric acetals and equilibration. Enone 6 is converted to the cis-decalinone derivative 17 with fragmentation as the key step. Consequently oxidation to the conjugated enedione 24 , reduction to the enediol 25 and intramolecular oxymercuration produces, depending on the reaction conditions, either the unsaturated tricyclic ether 27 , which constitutes a link to a known 18-deoxynargenicin synthesis, or the saturated tricyclic ether 26 , which represents the starting material for the construction of the tenmembered ring of nodusmicin.

The diketone3 was reduced to the diol which then was transformed to the tetracyclic diketal5 by treatment with sodium in ethanol. Protection of the remaining hydroxy group was followed by hydrolysis of the dimethylketal. The resulting ketone7 was stereoselectively converted to the tertiary alcohol by methyl magnesium chloride. Acidic retrograde aldol reaction of the tertiary alcohol led to the decalindione10, which was partially dehydrogenated by cupric chloride under basic conditions. The resulting endione1 cyclized by light induced hydrogen abstraction and collapse of the resulting diradical to the perhydronaphtho[1,8-bc]furan derivative.

Our first target on the way towards the synthesis of nodusmicin is the preparation of the title compound. Meso diol1 is partially etherified, then oxidized to the enone. The sterically compressed structure of this compound is the rationale of the highly stereoselective introduction of the substituents. (CH3)2CuLi introduces the methyl group and the enolate is captured as silylenol ether, which in turn is transformed to the α-hydroxyketone by OsO4. Reduction leads to the vicinaltrans diol. Protection of theexo-hydroxy group is followed by treatment with sodium in ethanol. Via intramolecular nucleophilic addition, substitution and dechlorination the tetracyclic diketal8 is formed. After exchange of the protective groups and partial hydrolysis of the ketals the tertiary alkohol is obtained with methyl Grignard reagent. Acidic fragmentation yields the desired title compound.

The applicability of the recently developed annulation method1,2 is demonstrated by the construction of regio- and stereospecifically substituted fused ring systems.

As an antagonist of the platelet activating factor, chatancin (1), which is isolated from a soft coral, is of potential therapeutic use. The first total synthesis [Eq. (1)] of this structurally unusual diterpene in racemic form is described along with the formal total syntheses of natural (+)-chatancin as well as unnatural (-)-chatancin.

4-tert-Butyl-3,4,5,6-tetrahydropyridine-1-oxide (1) and 6-butyl-3,4,5,6-tetrahydropyridine-1-oxide (2) were prepared and isolated in their monomeric forms. In many aprotic solvents these compounds are converted into their dimers. The main product in both cases is the addition product of identical enantiomers. In the case of compound1 a very small amount of an addition product of the optical antipodes is also formed, which is the thermodynamically most stable isomer. In contrast, compound2 yielded an addition product of the optical antipodes in larger amounts, with a thermodynamically less favourable structure. These dimerizations are solvent dependent, reversible and sensitive to steric hindrance.

As a first step toward total synthesis of histrionicotoxin and its congeners, the preparation of (±)-cis-Azaspiro[5.5]undecan-8-ol (11) is described.

Pentene-1 was added to the unsubstituted and to two alkylsubstituted 3,4,5,6-tetrahydropyridine-1-oxides. These reactions yielded mainly (exclusively) the product of axialexo addition, next to very small amounts of those ofendo addition, addition with inverse regiochemistry and of equatorial attack. The conformations of the major adducts were elucidated.

A variation of the recently described synthesis of porantherilidine leads to an intermediate, which can be converted to porantheridine as well as to porantherilidine.

4-tert-Butyl-3,4,5,6-tetrahydropyridine-1-oxide (1) and 6-Butyl-3,4,5,6-tetrahydropyridine-1-oxide (2) were selected to study the stereochemistry of 1,3-additions (nucleophilic additions) to these unsaturated six membered ring systems. Butylmagnesiumbromide, sodiumboronhydride and potassium cyanide were chosen as reagents. They added axially to1, but yielded mixtures of the two possible stereoisomeres with2.

The preparation of the title compounds is easily accomplished by cycloaddition of 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene with allylic and homoallylic alcohols yielding tetrachloronorbornene carbinols and their homologues resp., which cyclize under basic conditions by nucleophilic addition to the strained double bond. Dechlorination is achieved by simultaneous or subsequent treatment with sodium in refluxing ethanol. The range and limitations of this reaction sequence are discussed and the dependence of the reaction rate of the intramolecular nucleophilic addition on the structure, the nucleophilicity of the anionic entity and the presence of the chlorine atoms are demonstrated.

Zusammenfassung The synthesis of Porantheridine is described. Keystep of this synthesis is the 1,3-dipolar addition of a nitron to an alkene.

Adalin (1-Pentyl-9-azabicyelo[3.3.1]nonan-3-on, 1) ist das Abwehrsekret des europ~isehen Marienkgfers Adalia bipunktata L. 1, das yon Tursch, Braekman und Mitarbeitern isoliert wurde. Die Strukturaufklarung dieses Naturstoffes durch dieselben Autoren beruht auf spektroskopisehen Daten, R5ntgenstrukturanalyse und chemischen Umwandlungen 2 sowie auf einer Synthese 3. Die Ahnliehkeit des Reduktionsproduktes des Adalins, Dihydroadalin [(1R,3S)i-Pentyl-9-azabicyclo[3.3.1]nonan-3-ol] (2) mit neurophysiologiseh aktiven Alkaloiden wie den Tropaalkaloiden 4 und den Histrionieotoxinen~ bewog uns, eine Synthese des Adalins fiber die Zwisehenstufe des Dihydroadalins aufzubauen.

Smooth fragmentation of the strained title compounds under acidic conditions is achieved. Depending on structure, solvent, Lewis acid and nucleophile stereospecifically substituted cyclopentanones as well as cyclohexanones could be gained in good yields.

Der Austausch von phenolischen OH-Gruppen gegen Wasserstoff durch Hydrogenolyse von Athern der entsprechenden Phenole mit stickstoffhaltigen Heterocyclen wurde studiert.

Publisher Summary This chapter describes the novel amphibian toxins, their isolation, structure, and syntheses, the phenomenon of receptors that selectively bind to specific agents. The chapter also discusses the location and function of amphibious venoms; spiropiperidines, cis -decahydroquinolines, and octahydroindolizidines; neurotoxins, receptors, and ion transport. Amphibian venoms may offer only some passive protection. The venoms are located in skin glands, in some cases in the eggs of the species, and very rarely in the bloodstream. Tetrodotoxin and saxitoxin bind at receptor site 1 and block the ion transport activity of the sodium channel. The steroidal alkaloids batrachotoxin and, to a lesser degree, veratridine and the terpinoids aconitine and grayanotoxin, bind at receptor site 2, a common binding site probably in the sodium channel, belonging to a subunit exercising control over other subunits that must interact for the various functions of the sodium channel. Batrachotoxin is the most useful probe for biochemical studies of neurotoxin receptor site 2 on the sodium channel.