Fangming Kong

Cytotoxic peptides from the marine sponge Cymbastela sp.

Abstract Extracts of the sponge Cymbastela sp. have yielded the novel cytoloxic peptides geodiamolide G (II), hemiasterlin A (12), hemiasterlin B (13), criamide A (14) and criamide B (15). The structures of the new compounds were solved via speciroscopic analysis and chemical degradation.

Ingenamine alkaloids isolated from the sponge Xestospongia ingens: Structures and absolute configurations

Abstract Five new minor ingenamine alkaloids have been isolated from extracts of the sponge X. ingens collected in Papua New Guinea. The structures of the new metabolites were solved via spectroscopic analysis. Mosher ester methodology has been used to determine the absolute configurations of ingenamine (1), ingamine A (2) and ingenamine E (11). The results show that the ‘ingenamine’ alkaloids isolated from X. ingens are antipodal to the manzamines.

Ingamines A and B, new cytotoxic alkaloids from the marine sponge Xestospongia ingens

Abstract Ingamines A (2) and B (3), two novel cytotoxic alkaloids, have been isolated from the marine sponge Xestospongia ingens collected in Papua New

Ingenamine, a novel pentacyclic alkaloid from the marine sponge Xestospongia ingens

Ingenamine (1), a novel cytotoxic pentacyclic alkaloid, has been isolated from the marine sponge Xestospongia ingens collected in Papua New Guinea. The structure of ingenamine has been solved by extensive spectrosopic analysis.

Chapter Three 3-Alkylpiperidine alkaloids isolated from marine sponges in the order haplosclerida

Summary The first 3-alkylpiperidine sponge alkaloids, the halitoxins 31, were discovered less than twenty years ago [25]. Since that time, more than one hundred biogenetically related alkaloids have been isolated from marine sponges in the order Haplosclerida. As a group, the 3-alkylpiperidines are characterized by the diversity and complexity of their chemical structures and by the range of biological activities that they exhibit. To date there are eleven macrocyclic skeletons known among the 3-alkylpiperidine alkaloids. These include the haliclamine/cyclostellettamine, ingenamine, madangamine, ircinal, manzamine, halicyclamine, saraine 1-3, saraine A to C, petrosin, xestospongin/araguspongine and aragupetrosine skeletons shown in Figure 3.11. Three of these skeletal types, belonging to the ingenamine [52], madangamine [69] and halicyclamine alkaloids [42], were first reported in the single year 1994. In addition, it has recently been recognized that the papuamine [64] and manzamine C [58] skeletons are biogenetically related to the 3-alkylpiperidines. Therefore, the evidence to date indicates that the ammonia, propenal and long chain dialdehyde units that are the putative biogenetic precursors to the 3-alkylpiperidine alkaloids can be combined in a wide variety of ways to generate complex structures and it is reasonable to expect that many more alkaloid skeletal types will be discovered in Haplosclerida sponges in the years to come. The distribution of various 3-alkylpiperidine alkaloids over the five families of Haplosclerida forms a strong indication that this order of sponges is a monophyletic group, despite a recent attempt to subdivide it into two non-related units. The diversity of related 3-alkylpiperidine derivatives was utilized to explore phylogenetic relationships of the families. The results support the previously published schemes based on morphological characters. From the outset, 3-alkylpiperidine alkaloids have represented a substantial challenge to the extant methodology for chemical structure elucidation. For example, the monomeric units of the halitoxins are now well characterized but an effective molecular weight determination or description of the nature of oligomer/polymer termination has thus far proven elusive [25,28]. The difficulties associated with analyzing the NMR data for the long chain alkyl bridges spanning the nitrogen containing polycyclic cores has complicated the structure elucidation of most of the macrocyclic 3-alkylpiperdine alkaloids, occasionally leading to incorrect structural proposals. It is interesting to note that the saraines were first isolated in the early 1970s but their chemical structures were not elucidated until the 1980s when the availability of 2D experiments conducted on high field NMR spectrometers finally proved to be a powerful enough structural tool to meet the challenge of determining unambiguous connectivity in their long chain alkyl bridges [43,44,45,46]. Fortunately, several of the 3-alkylpiperidine alkaloids have given crystals suitable for X-ray diffraction analysis and this has provided solid evidence for the petrosin [32], xestospongin [35], saraine A to C [48], manzamine [57] and ingenamine skeletons [53]. 3-Alkylpiperidine alkaloids have been found to exhibit many types of biological activity suggesting potential for development into drugs. The cytotoxicity of the manzamines [57] and the vasodilatory properties of the araguspongines [37] have attracted the most attention. The combination of potent biological activity and structural complexity found in the 3-alkylpiperidine alkaloids has also caught the attention of synthetic chemists. To date there have been synthetic efforts undertaken towards the synthesis of manzamines A [71,90,91,92,93,94,95,96,97], C [98,99] and D, saraine A [100], petrosin [101], the xestospongins/araguspongines [40,102,103], and the ingenamines [71,72].

Pseudoaxinellin, a cyclic heptapeptide isolated from the papua new guinea sponge pseudoaxinella massa

Pseudoaxinellin (1), a new cyclic heptapeptide, has been isolated from the marine sponge Pseudoaxinella massa collected in Papua New Guinea. The structure of1 was solved by spectroscopic analysis and chemical degradation. Pseudoaxinellin is the first cyclic heptapeptide reported from a marine source. One of the amide bonds in 1 is cis.

Structure characterization of lipocyclopeptide antibiotics, aspartocins A, B & C, by ESI-MSMS and ESI-nozzle-skimmer-MSMS.

Three lipocyclopeptide antibiotics, aspartocins A (1), B (2), and C (3), were obtained from the aspartocin complex by HPLC separation methodology. Their structures were elucidated using previously published chemical degradation results coupled with spectroscopic studies including ESI-MS, ESI-Nozzle Skimmer-MSMS and NMR. All three aspartocin compounds share the same cyclic decapeptide core of cyclo [Dab2 (Asp1-FA)-Pip3-MeAsp4-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11]. They differ only in the fatty acid side chain moiety (FA) corresponding to (Z)-13-methyltetradec-3-ene-carbonyl, (+,Z)-12-methyltetradec-3-ene-carbonyl and (Z)-12-methyltridec-3-ene-carbonyl for aspartocins A (1), B (2), and C (3), respectively. All of the sequence ions were observed by ESI-MSMS of the doubly charged parent ions. However, a number of the sequence ions observed were of low abundance. To fully sequence the lipocyclopeptide antibiotic structures, these low abundance sequence ions together with complementary sequence ions were confirmed by ESI-Nozzle-Skimmer-MSMS of the singly charged linear peptide parent fragment ions H-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11-Dab2(1+)-Asp1-FA. Cyclization of the aspartocins was demonstrated to occur via the beta-amino group of Dab2 from ions of moderate intensity in the ESI-MSMS spectra. As the fatty acid moieties do not undergo internal fragmentations under the experimental ESI mass spectral conditions used, the 14 Da mass difference between the fatty acid moieties of aspartocins A (1) and B (2) versus aspartocin C (3) was used as an internal mass tag to differentiate fragment ions containing fatty acid moieties and those not containing the fatty acid moieties. The most numerous and abundant fragment ions observed in the tandem mass spectra are due to the cleavage of the tertiary nitrogen amide of the pipecolic acid residue-3 (16 fragment ions) and the proline residue-11 (7 fragment ions). In addition, the neutral loss of ethanimine from alpha,beta-diaminobutyric acid residue 9 was observed for the parent molecular ion and for 7 fragment ions.