http://www.mdpi.com/journal/marinedrugs/special_issues/marine-natural-products/ {snippet name="submission_info"} http://www.mdpi.com/1660-3397/8/4/835/ The salinosporamides are potent proteasome inhibitors among which the parent marine-derived natural product salinosporamide A (marizomib; NPI-0052; 1) is currently in clinical trials for the treatment of various cancers. Methods to generate this class of compounds include fermentation and natural products chemistry, precursor-directed biosynthesis, mutasynthesis, semi-synthesis, and total synthesis. The end products range from biochemical tools for probing mechanism of action to clinical trials materials; in turn, the considerable efforts to produce the target molecules have expanded the technologies used to generate them. Here, the full complement of methods is reviewed, reflecting remarkable contributions from scientists of various disciplines over a period of 7 years since the first publication of the structure of 1. http://www.mdpi.com/1660-3397/8/4/835/ Thu, 25 Mar 2010 00:00:00 CET Marine Drugs 2010-03-25 8 4 Review 835 880 1660-3397 Generating a Generation of Proteasome Inhibitors: From Microbial Fermentation to Total Synthesis of Salinosporamide A (Marizomib) and Other Salinosporamides 2010-03-25 doi: 10.3390/md8040835 Potts Lam http://www.mdpi.com/1660-3397/8/3/483/ 3-Alkyl pyridinium alkaloids (3-APAs) are common secondary metabolites in marine sponges of the order Haplosclerida. In recent years, our laboratory has isolated and synthesized several new members of this family such as haliclamines C–F, viscosamine, viscosaline and a cyclic monomer. All of them were isolated from the Arctic sponge Haliclona viscosa collected in Spitsbergen, Norway. In this article we report the syntheses of these secondary metabolites from Haliclona viscosa and related compounds and give a short overview of the bioactivity. http://www.mdpi.com/1660-3397/8/3/483/ Fri, 05 Mar 2010 00:00:00 CET Marine Drugs 2010-03-05 8 3 Review 483 497 1660-3397 Synthesis of 3-Alkyl Pyridinium Alkaloids from the Arctic Sponge Haliclona viscosa 2010-03-05 doi: 10.3390/md8030483 Christoph Timm Thorsten Mordhorst Matthias Köck http://www.mdpi.com/1660-3397/8/1/122/ Calyculins, highly cytotoxic polyketides, originally isolated from the marine sponge Discodermia calyx by Fusetani and co-workers, belong to the lithistid sponges group. These molecules have become interesting targets for cell biologists and synthetic organic chemists. The serine/threonine protein phosphatases play an essential role in the cellular signalling, metabolism, and cell cycle control. Calyculins express potent protein phosphatase 1 and 2A inhibitory activity, and have therefore become valuable tools for cellular biologists studying intracellular processes and their control by reversible phosphorylation. Calyculins might also play an important role in the development of several diseases such as cancer, neurodegenerative diseases, and type 2-diabetes mellitus. The fascinating structures of calyculins have inspired various groups of synthetic organic chemists to develop total syntheses of the most abundant calyculins A and C. However, with fifteen chiral centres, a cyano-capped tetraene unit, a phosphate-bearing spiroketal, an anti, anti, anti dipropionate segment, an α-chiral oxazole, and a trihydroxylated γ-amino acid, calyculins reach versatility that only few natural products can surpass, and truly challenge modern chemists’ asymmetric synthesis skills. http://www.mdpi.com/1660-3397/8/1/122/ Thu, 21 Jan 2010 00:00:00 CET Marine Drugs 2010-01-21 8 1 Review 122 172 1660-3397 Calyculins and Related Marine Natural Products as Serine- Threonine Protein Phosphatase PP1 and PP2A Inhibitors and Total Syntheses of Calyculin A, B, and C 2010-01-21 doi: 10.3390/md80100122 Annika E. Fagerholm Damien Habrant Ari M. P. Koskinen http://www.mdpi.com/1660-3397/7/4/705/ In his most celebrated tale “The Picture of Dorian Gray”, Oscar Wilde stated that “those who go beneath the surface do so at their peril”. This sentence could be a prophetical warning for the practitioner who voluntarily challenges himself with trying to synthesize marine sponge-deriving pyrrole-imidazole alkaloids. This now nearly triple-digit membered community has been growing exponentially in the last 20 years, both in terms of new representatives and topological complexity − from simple, achiral oroidin to the breathtaking 12-ring stylissadines A and B, each possessing 16 stereocenters. While the biosynthesis and the role in the sponge economy of most of these alkaloids still lies in the realm of speculations, significant biological activities for some of them have clearly emerged. This review will account for the progress in achieving the total synthesis of the more biologically enticing members of this class of natural products. http://www.mdpi.com/1660-3397/7/4/705/ Fri, 27 Nov 2009 00:00:00 CET Marine Drugs 2009-11-27 7 4 Review 705 753 1660-3397 A Submarine Journey: The Pyrrole-Imidazole Alkaloids 2009-11-27 doi: 10.3390/md7040705 Barbara Forte Beatrice Malgesini Claudia Piutti Francesca Quartieri Alessandra Scolaro Gianluca Papeo http://www.mdpi.com/1660-3397/7/4/654/ Xestenone is a marine norditerpenoid found in the northeastern Pacific sponge Xestospongia vanilla. The relative configuration of C-3 and C-7 in xestenone was determined by NOESY spectral analysis. However the relative configuration of C-12 and the absolute configuration of this compound were not determined. The authors have now achieved the total synthesis of xestenone using their developed one-pot synthesis of cyclopentane derivatives employing allyl phenyl sulfone and an epoxy iodide as a key step. The relative and absolute configurations of xestenone were thus successfully determined by this synthesis. http://www.mdpi.com/1660-3397/7/4/654/ Tue, 24 Nov 2009 00:00:00 CET Marine Drugs 2009-11-24 7 4 Article 654 671 1660-3397 Total Synthesis and Absolute Configuration of the Marine Norditerpenoid Xestenone 2009-11-24 doi: 10.3390/md7040654 Koichiro Ota Takao Kurokawa Etsuko Kawashima Hiroaki Miyaoka http://www.mdpi.com/1660-3397/7/3/314/ Because of the highly unique structures of marine natural products, there are many examples of structures that were originally proposed based on spectral analyses but later proven incorrect. In many cases, the total syntheses of the originally proposed structures of marine natural products has confirmed their incorrectness and the subsequent total syntheses of the newly proposed structures proved the revised structures. This review will show such cases appearing after 2005 and demonstrate how the true structures were elucidated. http://www.mdpi.com/1660-3397/7/3/314/ Mon, 13 Jul 2009 00:00:00 CEST Marine Drugs 2009-07-13 7 3 Review 314 330 1660-3397 Recent Synthetic Studies Leading to Structural Revisions of Marine Natural Products 2009-07-13 doi: 10.3390/md7030314 Yoshihide Usami http://www.mdpi.com/1660-3397/7/2/249/ Seco-chaetomugilins A and D were isolated from a strain of Chaetomium globosum that was originally isolated from the marine fish Mugil cephalus, and their absolute stereostructures were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, along with the chemical transformation from known chaetomugilins A and D. Seco-chaetomugilin D exhibited growth inhibitory activity against cultured P388, HL-60, L1210, and KB cells. http://www.mdpi.com/1660-3397/7/2/249/ Tue, 16 Jun 2009 00:00:00 CEST Marine Drugs 2009-06-16 7 2 Article 249 257 1660-3397 New Azaphilones, Seco-Chaetomugilins A and D, Produced by a Marine-Fish-Derived Chaetomium globosum 2009-06-16 doi: 10.3390/md7020249 Takeshi Yamada Yasuhide Muroga Reiko Tanaka