Studies on azaspiracid biotoxins. II. Mass spectral behavior and structural elucidation of azaspiracid analogs

In this report, the mass spectral analysis of azaspiracid biotoxins is described. Specifically, the collision-induced dissociation (CID) behavior and differences between CID spectra obtained on a triple-quadrupole, a quadrupole time-of-flight, and an ion-trap mass spectrometer are addressed here. The CID spectra obtained on the triple-quadrupole mass spectrometer allowed the classification of the major product ions of the five investigated compounds (AZA 1-5) into five distinct fragment ion groups, according to the backbone cleavage positions. Although the identification of unknown azaspiracids was difficult based on CID alone, the spectra provided sufficient structural information to allow confirmation of known azaspiracids in marine samples. Furthermore, we were able to detect two new azaspiracid analogs (AZA 1b and 6) in our samples and provide a preliminary structural analysis. The proposed dissociation pathways under tandem mass spectrometry (MS/MS) conditions were confirmed by a comparison with accurate mass data from electrospray quadrupole time-of-flight MS/MS experiments. Regular sequential MS(n) analysis on an ion-trap mass spectrometer was more restricted in comparison to the triple-quadrupole mass spectrometer, because the azaspiracids underwent multiple [M + H - nH(2)O](+) (n = 1-6) losses from the precursor ion under CID. Thus, the structural information obtained from MS(n) experiments was somewhat limited. To overcome this limitation, we developed a wide-range excitation technique using a 180-u window that provided results comparable to the triple-quadrupole instrument. To demonstrate the potential of the method, we applied it to the analysis of degraded azaspiracids from mussel tissue extracts.     

Iridoide aus Verbascum nigrum L. 182. Mitteilung über organische Naturstoffe

Iridoids from Verbascum nigrum L. Two new iridoid glycosides, nigroside 1 ( ? 6-O-(3-O-einnamoyl-α-L-rhamno-pyranosyl)aucubin (2) , and nigroside 2 (?6-O-(2-O-cinnamoyl-α-L-rhamnopy-ranosyl)aucubin (3) , and the known compound laterioside (1) have been isolated from extracts of the stems of Verbascum nigrum L., and their structures established primarily on the basis of NMR. spectroscopy. Harpagoside (4) , a known iridoid glucoside, was also isolated from the roots of this plant.     

The crystal structure of barium manganese(II) iron(III) fluoride BaMnFeF7

The crystal structure of the monoclinic compound BaMnFeF₇ has been determined: a = 553.2(1), b = 1098.0(2), c = 918.3(1) pm, β = 94.67(1)°, V = 555.9(3) × 10^?24 cm³, Z = 4. All atoms are in general positions of space group $\text{P2}{}_1\text{c}$, weighted R = 0.031, using 1771 independent single-crystal reflections with I > 2σ(I). The structure consists of edge-sharing dinuclear Mn₂F^6?₁₀ units (MnMn = 322.2 pm), linked via corners by intermediate FeF₆ octahedra, at which two cis ligands remain unbridged. The average distances in the distorted octahedra are MnF = 211.6 pm and FeF = 192.7 pm. The barium atoms are irregularly 12-coordinated with a mean distance BaF = 290.5 pm. The structure is discussed in relation to the trigonal weberite Na₂MnFeF₇ and others.     

An Unexpected Asymmetric Reduction of 4-(1-Nitro-2-oxocyclododecyl)butan-2-one. Determination of the absolute configuration of (‒)-15-hexadecanolide

Reduction of the carbonyl group in the side chain of 4-(1-nitro-2-oxocyclododecyl)butan-2-one ( 3 ) with organoboron complexes are influenced by the chiral center, in 4-position with respect to the carbonyl C-atom, to which the NO₂ group is attached, a rare type for an asymmetric reduction. Independent of the (R)- or (S)-configuration of the Alpine-Hydride, (+)- 3 is reduced only to the (15S)-nitrolactone (+)- 5 and, after subsequent transformations, to (+)-(-S)-15-hexadecanolide ((+)- 1 ), enantiomer of the naturally occurring (?)- 1 .     

Umbellamin,ein neues «dimeres» Indolalkaloid 130. Mitteilung über Alkaloide [1]

Umbellamine (f; C₄₁H₄₈N₄O₄), a «dimeric» indole-indoline alkaloid, was isolated from the root bark of Hunteria umbellata (K. SCHUM .) HALL . F.; it is probably identical with the alkaloid hunterine (structure unknown) of NeUSS & CONE [14]. Thermolysis yielded (+)-eburnamenine (II), whereas a detailed mass spectrometric study of I, of its O-methyl and O-acetyl derivatives, and also of the derived diol V revealed the presence of a phenolic hydroxy-pseudoakuammigine group as second part, the benzene nucleus of the latter being linked to the C-14 atom of the eburnamenine component (present in the dihydrom form). The n.m.r. study of umbellamine and of its derivatives showed that the phenolic hydroxy group is either at C-10′ or C-11′ and that the dihydroeburnamenyl residue is connected to C-11′ or C-10′ of the pseudoakuammigine residue. A choice between these alternatives was possible by investigation of the hydroxylated base IX arising from the latter component, and obtained in small quantities by treatment of umbellamine with zinc or tin in acid. Its constitution, deduced by uv., n.m.r. and mass spectrometry, suggested that the hydroxy group is fixed at C-11′. If this is correct, the dihydrocburnatnenyl residue is linked to C-10′ of the pseudoakuarnmigine residue. Thus we propose formula I for umbellamine.     

Photochemische reaktionen von äthern mit 4-methylcinnolin und chinoxalinen

1. 4-Methylcinnoline on irradiation in ethers produces the photoproducts 2–6 by a 1.4 addition of the ethers. 2. Quinoxaline reacts with ethers to produce the quinoxalines 8, 12 and 13 by what appears superficially to be a substitution process. Reaction of 2,3-dimethylquinoxaline with tetrahydrofuran gives as the main product 16 by 1.2 addition, and 2-(t-butyl)-quinoxaline gives the dihydroquinoxaline derivatives 17a, b . Because of the known easy autoxidation of 1,2-dihydroquinoxaline we believe that the intermediate in the photolytic reaction of quinoxaline, yielding 8, 12 and 13 , is also the 1.2 addition product. 3. The mass-spectrometric behaviour of the cinnoline and quinoxaline derivatives has been discussed.     

(C5H5)Co(P(O)(OH)2)3H]: a novel organometallic tris-phosphonic acid that dissolves glass to form a six-coordinate silicon complex

The sodium salt of the tripodal oxygen ligand Na[(C5H5)Co(P(O)(OMe)2)3] (1) reacts with gaseous hydrogen chloride in dichloromethane to give sodium chloride and [(C5H5)Co(P(O)(OMe)2)3H2]Cl (2). Addition of an equimolar amount of 1 leads to precipitation of sodium chloride again to yield the acid form of the ligand [(C5H5)Co(P(O)(OMe)2)3H] (3). Its solid-state structure contains a very short intramolecular OH.O hydrogen bond. The compound hydrolyses in boiling water to give methanol and the title complex [(C5H5)Co(P(O)(OH)2)3H] (4). This complex is a rather strong tris-phosphonic acid (pK(a1) 2.0, pK(a2) 4.0, pK(a3) 6.3, and pK(a4) 9.6). Attempts to grow single crystals of this highly water-soluble yellow crystalline compound lead to the silicon complex [((C5H5)Co[P(O)(OH)2]2[P(O)2(OH)])(2)Si].8 H2O (5). The crystal structure determination shows that it is a molecular complex of two tris-phosphonic acids that each act as a tris-chelating ligand. Additional water molecules form a complex net of hydrogen bonds between the complexes of 5. The SiO6 octahedron is only insignificantly distorted with Si-O bond lengths of 1.78 A. Complex 4 reacts with stoichiometric amounts of potassium carbonate to yield the potassium salt K[(C5H5)Co(P(O)(OH)2)3] (6). The crystal structure of 6 has also been determined. In the solid state it is a two-dimensional coordination polymer with each potassium ion being coordinated by twelve oxygen atoms of six tris-phosphonic acids.     

Synthese der Spermidin-Alkaloide (±)-Inandenin-10-ol,Inandenin-10-on und (±)-Oncinotin

Syntheses of the Spermidine Alkaloids (±)-Inandenin-10-ol, Inandenin-10-one, and (±)-Oncinotine New syntheses of the title compounds using two-ring-enlargement reactions are described. Starting from the aldehyde 1 , the corresponding 4′-aza derivative 15 could be obtained by reductive amination with the appropriate and protected spermidine derivative 14 (Scheme 4). Enlargement of the carbocyclic ring in 15 by five members gave, after further transformations, the hydroxylactam 18 . Transamidation of 18 , the second ring-enlargement step, led to (±)-inandenin-10-ol (7;22.9% overall yield) and, after oxidation, to inandenin-10-one ( 8 ; 22.5%, overall yield). (±)-Oncinotine 6 was synthesized by two pathways (Scheme 6): protection of the terminal NH₂ group by treatment with the Nefkens reagent and replacement of the OH group by Cl gave 24 , which by thermal transamidation followed by direct ring closure led to the oncinotine derivative 26 . The same intermediate could be obtained in higher yield via 28 by oxidation and protection of 18 followed by transamidation and reductive ring closure. Treatment of 26 with hydrazine finally gave (±)-oncinotine 6 in 15.9% overall yield.