Macrocyclische Spermidinalkaloide aus Maytenus tnossambicensis (KLOTZSCH) BLAKELOCK 12. Mitteilung über Celastraceen-Inhaltsstoffe

Macrocyclic Spermidine Alkaloids from Maytenus mossambicensis (KLOTZSCH) BLAKELOCK In addition to celabenzine ( 1 ), three new macrocyclic spermidine alkaloids cyclocelabenzine ( 2 ), isocyclocelabenzine ( 3 ) and hydroxyisocyclocelabenzine ( 4 ) have been isolated from Maytenus mossambicensis (klotzsch) blakelock, var. mossambicensis. The three alkaloids show the 13-membered lactam ring of celabenzine being linked to the benzoyl residue within the spermidine unit. Hydroxyisocyclocelabenzine ( 4 ) is the first known spermidine alkaloid with a hydroxy function at the macrocyclus. The structural elucidation was based mainly on spectroscopic methods, specially ¹H- and ¹³C-NMR. spectroscopy.     

Macrocyclische Spermidinalkaloide aus Pleurostylia africana LOES. 9. Mitteilung über Celastraceen-Inhaltsstoffe

Macrocyclic Spermidine Alcaloids from Pleurostylia africana LOES . The structure of pleurostyline, a new macrocyclic spermidine alkaloid from Pleurostylia africana (Celastraceae), has been elucidated mainly by ¹H- and ¹³C-NMR.-spectroscopy. Pleurostyline represents a new structure type in which spermidine is incorporated in a 13-membered lactam ring to which an additional cinnamoyl residue is fused to yield a 7-membered ring. The same plant contains also the spermidine alkaloids celacinnine and cellallocinnine of which ¹³C- and high field ¹H-NMR.-measurements have been carried out for the first time. Both alkaloids are interconvertible by UV.-irradiation. In addition the existence of rotational isomerism of one amide group of these alkaloids has been demonstrated by NMR.-spectroscopy.     

Inhibition of blood coagulation factor XIIIa-mediated cross-linking between fibronectin and collagen by polyamines

Soluble fibronectin is found in body fluids and media of cultured adherent cells. Insoluble fibronectin is found in tissue stroma and in extracellular matrices of cultured cells. Fibronectin is a substrate for factor XIIIa (plasma transglutaminase) and can be cross-linked to collagen and to the alpha chain of fibrin. We have used sodium dodecyl sulfate-polyacrylamide gel electrophoresis to investigate the possibility that factor XIIIa-mediated cross-linking is influenced by polyamines. Spermidine inhibited cross-linking between fibronectin and type I collagen, isolated alpha 1 (I) collagen chains, or iodinated cyanogen bromide fragment 7 of alpha 1 (I) chains (125I-alpha 1 (I)-CB7). Half-maximal inhibition of cross-linking between 125I-alpha (I)-CB7 and fibronectin was observed when 0.1 mM spermine or spermidine was present. Spermidine, 0.7 mM, partially inhibited cross-linking between fibronectin and the alpha chain of fibrin but failed to inhibit cross-linking between the fibrin monomers of a fibrin clot. Spermidine also failed to inhibit cross-linking between fibronectin molecules when aggregation of fibronectin was induced with dithiothreitol. In contrast, 0.7 mM monodanyslcadaverine inhibited fibronectin-collagen, fibronectin-fibrin, fibronectin-fibronectin, and fibrin-fibrin cross-linking. Spermidine or spermine, 0.7 mM, enhanced the cross-linking between molecules of partially amidinated fibronectin, suggesting that N1,8-(di-gamma-glutamyl)-polyamine cross-linkages were formed. Spermidine and spermine failed to enhance cross-linking between monomers of amidinated fibrin. These results indicate that physiologic concentrations of polyamines specifically disturb transglutaminase-catalyzed cross-linking between fibronectin and collagen.     

Synthese von selektiv N- funktionalisierten Polyamin-Derivaten

Synthesis of Selectively N-Functionalized Polyamine Derivatives A threefold differently protected derivative 8 of the triamine spermidine ( 2 ) has been prepared in three steps starting from propane-1,3-diamine ( 1 ). The protected spermidine derivative 8 was converted to its spermine analogue 12 , a useful polyamine intermediate. In a convergent way, the fourfold differently protected derivative 18 of the tetraamine spermine ( 3 ) has been obtained by coupling the two different and separately prepared propane-1,3-diamine units 15 and 17 . Spermidine derivative 19 and spermine derivative 20 , both selectively protected at both primary amino groups, have been Prepared from the free polyamines 2 and 3 , respectively, in a direct approach.     

The polyamines of Xanthium strumarium and their response to photoperiod

Flowering plants of Xanthium strumarium L., grown in 8 h photoperiods, were analysed for polyamines. Putrescine, spermidine and spermine were found throughout the plant in three forms: (a) as free polyamines; (b) conjugates soluble in 5% trichloracetic acid (TCA); and (c) bound to the TCA-insoluble precipitate. On a fresh weight basis, total polyamines are most abundant in young leaves and buds, especially flower buds. Spermidine predominates in the free polyamine fractions, while spermine is dominant in the conjugated fraction. Transfer of vegetative plants from 16 h photoperiods to 1, 2, 3, or 4 inductive cycles (8 h light + 16 h uninterrupted dark) caused rapid and marked changes in the polyamine titer of the leaves and ultimately, floral initiation. The titer of free putrescine per mg protein declined progressively with induction in all leaf sizes, while the titers of free spermidine and spermine rose during days 2 and 3 in small and expanding leaves. Conjugated putrescine, spermidine and spermine rose sharply after only 1 inductive cycle, especially in small and expanding leaves, and maintained the higher level for at least several cycles. In plants given 4 inductive cycles, buds harvested after 4 additional days had sharply elevated levels of conjugated polyamines, especially spermine, on a protein basis.     

Polyamine distribution in the rat intestinal mucosa

As the first step in a study of mucosal polyamine metabolism during intestinal adaptation, we have measured mucosal polyamine concentrations at different sites along the normal rat intestine. Putrescine, spermidine, spermine and cadaverine were measured by spectrofluorometric analysis after thin-layer chromatography of their dansylated derivatives. Spermidine was present in the largest amounts at each of the sampling sites. The ratio of the concentration of spermidine to that of spermine paralleled the established pattern of cellular proliferation in the normal intestine as did the putrescine concentration (nmol per 10 cm) which decreased from duodenum to colon. These results provide the essential background to an assessment of the role of polyamines in the intestinal adaptive response.     

The Analgesic Properties of Corydalis yanhusuo

Corydalis yanhusuo extract (YHS) has been used for centuries across Asia for pain relief. The extract is made up of more than 160 compounds and has been identified as alkaloids, organic acids, volatile oils, amino acids, alcohols, and sugars. However, the most crucial biological active constituents of YHS are alkaloids; more than 80 have been isolated and identified. This review paper aims to provide a comprehensive review of the phytochemical and pharmacological effects of these alkaloids that have significant ties to analgesia.     

5,6-Dihydropyrrolo[2,1-b]isoquinolines as scaffolds for synthesis of lamellarin analogues

Efficient modular synthetic routes to open chain marine alkaloids such as lamellarins have been developed. 5,6-Dihydropyrrolo[2,1-b]isoquinoline scaffolds were prepared, and protocols enabling regioselective bromination followed by Suzuki cross-coupling were established for the introduction of aryl groups onto the 2- and 3-positions.     

Synthese von N-(4-Aminobutyl)-16-aza-19-nonadecanlactam und N-(4-Aminobutyl)-17-aza-20-icosanlactam (Desoxoinandenin)

Synthesis of N-(4-Aminobutyl)-16-aza-19-nonadecanelactam and N-(4-Aminobutyl)-17-aza-20-icosanelactam (Desoxoinandenine) According to Scheme 1, the two homologous macrocyclic spermidine derivatives 12 and 23 were synthesized. Key steps in both cases were two different types of ring-enlargement reactions. Compound 12 was identical with a degradation product of the naturally occurring spermidine alkaloids of inandenine-type.     

Bioorganic studies on marine natural products--diverse chemical structures and bioactivities

The discovery of new molecules contributes to the development of basic scientific concepts, leads to valuable drug-oriented compounds, and suggests possible new pharmacological reagents. Newly discovered substances can even be responsible for the creation of new scientific fields. Due to the radically different habitats of marine organisms, several notable examples of secondary metabolites from marine organisms have been isolated. Two of the most remarkable properties of these compounds are their structural and physiological diversities. These bioactive compounds are candidates for drugs or biological probes for physiological studies. Palytoxin is a polyol compound that shows extreme acute toxicity. Halichondrins are remarkable antitumor macrolides from sponge. Pinnatoxins, potent shellfish poisons, cause food poisoning. This paper describes bioorganic studies on such newly discovered wonders of nature. Several bioactive marine alkaloids and important substances involved in dynamic ecological systems are also described.     

Structure of macrocyclic alkaloids, oncinotin and isoocinotin

Two new macrocyclic alkaloids oncinotine ( 1 ) and isooncinotine ( 2 ) have been isolated from Oncinotis nitida BENTH . 1 can be converted into 2 by an amide exchange reaction. The spermidine residue was present in both bases. The structural elucidation was based mainly on (I) the determination of the functional groups, (II) degradation to compounds 12 and 13 and (III) mass spectrometric investigation of 1 and of the above mentioned degradation products.     

Macrocyclic Spermine Alkaloids from Verbascum: Isolation,Structure Elucidation,and Syntheses of the (E/Z)-Isomeric Pairs (S)-Verbasikrine/(S)-Isoverbasikrine and (S)-Verbamekrine/(S)-Isoverbamekrine

The isolation and structure elucidation of the 17-membered macrocyclic spermine alkaloids (S)-verbasikrine ( 3 ), (S)-isoverbasikrine ( 6 ), (S)-verbamekrine ( 9 ), and (S)-isoverbamekrine ( 12 ) is presented. The syntheses of their racemates are described. The HPLC/APCI-MS analysis of the original total alkaloid extract of Verbascum pseudonobile is presented.     

Macrocyclic Spermine Alkaloids from Verbascum: The (E/Z)-Isomeric Pairs (−)-(S)-Verbasitrine/(−)-(S)-Isoverbasitrine and (+)-(S)-Verbametrine/(+)-(S)-Isoverbametrine: Isolation,Structure Elucidation,and Synthesis

The isolation and structure elucidation of the 17-membered macrocyclic spermine alkaloids (−)-(S)-verbasitrine ( 2 ), (−)-(S)-isoverbasitrine ( 4 ), (+)-(S)-verbametrine ( 6 ), and (+)-(S)-isoverbametrine ( 8 ) is presented. The synthesis of their racemates is described.     

Estimation of urinary diamines and polyamines by thin-layer chromatography

The dansylated derivatives of ammonia, 1.3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, spermidine, histamine, and spermine were separated by one ascending development in chloroform—triethylamine (5:1) on a 250-μm silica gel 60 plate. Putrescine, cadaverine, spermidine, and spermine in human urine were quantitated by a direct scan of the fluorescent intensity of the spots corresponding to these compounds. Higher amounts of spermidine and spermine were found in the urines of cancer patients compared to the values of these substances in normal urine.     

HPLC analysis of polyamines and their acetylated derivatives in the picomole range using benzoyl chloride and 3,5-dinitrobenzoyl chloride as derivatizing agent

Analytical methods are described for the quantitative determination of putrescine, cadaverine, spermidine, spermine and the acetylated derivatives of spermidine and spermine in biological fluids using pre-column derivatization with either benzoyl chloride or 3,5-dinitrobenzoyl chloride, which were added to each sample as solutions in diethyl ether. Putrescine, spermidine and spermine can be analysed in seminal plasma at nanogram levels when benzoyl chloride is used as derivatizing agent. In the analysis of putrescine, cadaverine, spermidine and acetyl derivatives of spermidine and spermine, higher sensitivity is obtained with 3,5-dinitrobenzoyl-chloride. This method can readily be used in the determination of acetylated polyamines in urine samples.     

The Syntheses of Cyclic Spermine Alkaloids: Analogues of Buchnerine and Budmunchiamine C

The syntheses of two macrocyclic spermine alkaloids, analogues 1 and 2 of budmunchiamine C and buchnerine, in which N,N′‐bis(2‐aminoethyl)hexane‐1,6‐diamine (PA 262; 4 ) replaces spermine as polyamine backbone, were accomplished by two different methods. The first synthetic approach was based on a metal‐template intramolecular amidation of tetraamino esters prepared from a Michael addition of protected PA 262 10 to ethyl hexadec‐2‐ynoate ( 12 ) and ethyl prop‐2‐ynoate 17 , respectively (see Schemes 4 and 5, resp.). The consecutive Michael addition of ethane‐1,2‐diamine to unsaturated esters and aminolysis was employed in the second synthetic approach to prepare the precursors 23 and 24 (Scheme 6). The macrocyclic lactams were then constructed by macrocyclization of sulfonamido derivatives 25 and 26 in DMF with Cs₂CO₃ as catalyst.     

Complex Formation of Crown Ethers with the Cucurbit[6]uril–Spermidine and Cucurbit[6]uril–Spermine Complex in Aqueous Solution

Alkyl amines are able to form complexes with either crown ethers or cyclodextrins or cucurbit[6]uril. The same is known for polyamines such as spermidine and spermine. However, the simultaneous formation of such polyamines with crown ethers and cucurbit[6]uril has not been studied. The ability of polyamines such as spermidine and spermine to form mixed complexes with different ligands, e.g. crown ethers and cucurbit[6]uril has been studied in aqueous solution using pH-metric and calorimetric titrations. The thermodynamic data of reaction between crown ethers with spermidine, spermine and their cucurbit[6]uril complexes have been determined. The presence of cucurbit[6]uril on the polyamines has no important influence upon the reaction of these amines with crown ethers. The reactions between polyamines, cucurbit[6]uril and crown ethers are simple examples for the self organization of molecules due to specific interactions. Received in final form: 26 January 2005     

Asymmetric Synthesis of the Alkaloids mayfoline and N(1)-acetyl-N(1)-deoxymayfoline

The total syntheses of the spermidine alkaloids (?)-mayfoline ( 11 ) and (+)-N(1)-acetyl-N(1)-deoxymayfoline ( 12 ) are described. These macrocyclic lactams belong to the most interesting conjugates of the polyamine derivatives very commonly found in nature. The enantioselective syntheses were achieved through resolution of the methyl 3-amino-3-phenylpropanoate ( 2 ) by recrystallization of its (+)-L -tartrate salt. Construction of the 13-membered ring ensued through condensation, reductive ring expansion (internal bond cleavage), and finally a transamidation reaction involving a second ring expansion.     

Two New Spermidine Alkaloids from Chisocheton weinlandii

The investigation of the MeOH extract of the leaves of Chisocheton weinlandii Harms (Meliaceae) revealed two new open‐chain spermidine alkaloids, chisitine 1 ( 1 ) and chisitine 2 ( 2 ). Their structures were elucidated by NMR spectroscopy, tandem‐mass spectrometry, and independant syntheses (Scheme 3). Detailed MS/MS fragmentation pathways are discussed for both compounds based on H/D exchange and ¹⁸O‐labeling experiments (Schemes 1 and 2).     

Simultaneous Determination of Food-Related Amines by High-Performance Liquid Chromatography

Abstract

Ten amines found in marine foods, dimethylamine, trimethylamine, trimethylamine oxide, ammonia, urea, histamine, cadaverine, putrescine, spermine and spermidine were separated by HPLC using an ion-moderated partition column. Optimum resolution and sensitivity were obtained using 0.003N sodium hydroxide as the mobile phase and UV detection at 208 nm.