A new tetracyclic bis-piperidine alkaloid, neopetrosiamine A (1), has been extracted from the marine sponge Neopetrosia proxima collected off the west coast of Puerto Rico. The structure of compound 1 was elucidated by analysis of spectroscopic data coupled with careful comparisons of its 1 H and 13 C NMR data with those of a well-known 3-alkylbispiperidine alkaloid model. The new alkaloid displayed strong in vitro cytotoxic activity against a panel of cancer cell lines as well as in vitro inhibitory activity against the pathogenic microbes Mycobacterium tuberculosis and Plasmodium falciparum.
KeywordsNeopetrosia proxima; Bis-piperidine alkaloid; Cytotoxicity; Caribbean sponge; Tuberculosis; Malaria Marine sponges belonging to the order Haplosclerida constitute an abundant source of 3-alkylpyridine and 3-alkylpiperidine alkaloids, and thus far, well over 100 such alkaloids have been identified from this taxonomically complex group of marine organisms. 1,2 The occurrence of these biosynthetically intriguing families of alkaloids in sponges other than the Haplosclerida has also been described, albeit far less frequently. 3 Thus far, over 30 distinct 3-alkylpiperidine-based carbon frameworks have been discovered, including the haliclamine/ cyclostellettamine, ircinal, ingenamine, petrosin, mandangamine, manzamine, halicyclamine, sarain, xetospongin/araguspongine, and aragupetrosine skeletons. 2b,4 Not surprisingly, several of these compounds have been the subject of recent total syntheses, thanks in no small part to their interesting biological activities and the observation that they usually possess symmetry relationships that challenge the most basic hypotheses as to the cyclization processes responsible for their biosynthesis. [5][6][7] The most recently discovered class of tetracyclic bispiperidine alkaloids from marine sponges is perhaps best exemplified by the halicyclamines/ haliclonacyclamines (isolated from Haliclona sponge specimens), 8,9 the arenosclerins (isolated from Arenosclera brasiliensis and Pachychalina alcaloidifera) 10 and halichondramine (isolated from a Halichondria species). 11 * Corresponding author. abrodriguez@uprrp.edu.
Supplementary dataSupplementary data (underwater photograph of Neopetrosia proxima, copies of the 1 H and 13 C NMR spectra as well as 2D NMR spectra of neopetrosiamine A) associated with this article can be found, in the online version, at doi:xxxxxxxx.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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