Progress on lamellarins

Abstract

5This review covers recent literature on the lamellarins, a family of marine natural products, and related analogs, encompassing synthetic strategies for total synthesis, structure-activity relationships (SAR), and studies on mechanisms of biological action, namely in the context of antitumor activity. It reviews work published

A High‐Yielding Modular Access to the Lamellarins: Synthesis of Lamellarin G Trimethyl Ether, Lamellarin η and Dihydrolamellarin η

“…This approach compares most favourably with all other syntheses of this compound reported to date and surpasses the hitherto most efficient general and restricted protocols (Yadav et al, 2009: [7g] 44 % overall, uses molecular symmetry and has not been extended to other lamellarins; Ruchirawat et al, 2001: [6a, 7b] 27 % overall, general applicability demonstrated). [13] An updated comparison [7h] of syntheses of 1 a can be found in the Supporting Information. Our scalable procedure could be extended without any difficulties to the total synthesis of the 5,6-unsaturated lamellarin h (1 e) as well as its dihydro analogue 1 c in overall yields of 54 (10 steps) and 59 % (9 steps), respectively, and does not involve any expensive reagents or catalysts.…”

Synthesis of (Z)‐N‐Alkenylazoles and Pyrroloisoquinolines from α‐N‐Azoleketones through Pd‐Catalyzed Tosylhydrazone Cross‐Couplings

“…[19,20,21] It is worth noting that the pyrroloA C H T U N G T R E N N U N G [2,1-a]isoquinoline substructure is present in lamellarins, a class of marine natural products with useful biological properties such as antitumor and anti-HIV activities. [22] Taking into consideration that the starting ketones 1 are readily prepared from the corresponding NÀH azoles and bromoketones, this methodology may represent a highly modular approach for the preparation of this class of heterocycles.…”

Alkaloids from Marine Invertebrates as Important Leads for Anticancer Drugs Discovery and Development

“…The current good possibility that cephalostatin/ritterazine alkaloids inhibit cancer cell growth by affecting a novel molecular target(s), the ongoing total synthetic and SAR challenges, the possibility of locating a marine microorganism source actually responsible for their biosynthesis, and clinical development prospects all suggest that the bis steroidal alkaloids field will become increasingly productive and useful. Among the most promising anti-cancer drug candidates derived from marine invertebrates is the family of lamellarins [37][38][39][40][41]. The lamellarins form a group of more than 50 highly condensed DOPA-derived pyrrole alkaloids that have attracted researchers' interest due to both their structural originality and significant biological properties.…”

“…This DNA interaction, although relatively weak, provides the necessary anchorage for stabilization of the enzyme-DNA complex. Inhibition of topoisomerase I by lamellarin D has been demonstrated by a variety of approaches, both in vitro (using recombinant enzymes and model DNA substrates) and in a cellular context, using immunoblot assays to detect the drug-stabilized topoisomerase I-DNA complexes in cells [40,41].…”

“…Elegant synthetic routes to lamellarins or their key intermediates have been developed, which afforded sufficient quantities of structurally simplified lamellarin analogs for SAR and other biological studies [39,41]. In an early attempt to correlate the structures of lamellarins with their cytotoxic activities, Quesada et al, observed that an increase in the number of methylations and/or methoxylations appears to cause a decrease in the antitumor activities of the 13 lamellarins tested in their studies [51].…”