Special Issue "Alkaloid Analogs"

Guest Editor
Prof. Dr. Sadanandan E. Velu
Department of Chemistry, CHEM-280, The University of Alabama at Birmingham 901, 14th Street South, Birmingham, AL 35294-1240, USA
Website: http://main.uab.edu/chemistry/show.asp?durki=75828&site=3429&return=69934
E-Mail:
Interests: bioactive marine alkaloids; analogues; synthesis; anti-cancer; anti-infective; enzyme inhibitors; structure based drug design; fragment based drug design; in silico virtual screening; SAR studies; lead optimization

• marine alkaloid
• analog
• synthesis
• cytotoxic
• anticancer
• anti-inflammatory
• antibacterial
• antimalarial
• antiviral
• Indole
• Imidazole
• pyrrole
• carboline
• quinoline
• isoquinoline
• carbazole
• pyrroloquinoline
• quinone
• pyrroloquinone
• pyrroloiminoquinone

Title: Synthesis of (±)–Stemonamide, (-)–Cephalotaxine, and Related Alkaloids Using a Radical Cascade.
Author: Hiroyuki Ishibashi
Affiliation: School of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan
Abstract: Syntheses of (±)–stemonamide, (-)–cephalotaxine, and related alkaloids using radical cascade reactions, that involve a 7-endo-trig cyclization of alkyl or aryl radical followed by a 5-endo-trig cyclization of resulting alpha-amidoyl radical, are presented, Thus, Bu3SnH-mediated radical cyclization of compound, prepared from 1,2-cyclopentanedione, gave the radical cascade products as two stereoisomers in a ratio of ca. 1:1, which were then converted into to (±)–stemonamide and (±)–isostemonamide. A similar radical cyclization of compound, prepared form (3R,4R)-3,4-di(silyloxy)cyclopentanone, afforded radical cascade product, which was transformed into (-)–cephalotaxine. A synthetic intermedaite for (-)–cephalotaxine was converted into cephalezomine H.

Title: Imine and Iminium Agents in Marine Alkaloids
Authors: Peter Kovacic ¹ and Ratnasamy Somanathan ^1,2
Affiliations: ¹.Department of Chemistry, San Diego State University, San Diego, CA 92182-1030 USA
² Centro de Graduados e Investigación del Instituto Tecnológico de Tijuana, Apdo postal 1166, Tijuana, B.C., Mexico
Abstract: There is much evidence for participation of electron transfer (ET) functionalities in the physiological action of drugs and toxins. The main ET agents, usually formed as metabolites, are quinones, metal complexes, aromatic nitro compounds or iminium and imine species. The last category is the least well known. This review documents various imine and iminium agents in the marine alkaloid category. The conjugated members of those classes have the potential of participating in ET reactions which can generate reactive oxygen species or become involved in the central nervous systems. In addition, examples of imines and iminiums in other bioactive classes are provided along with data on physiological activity, ROS generation and electron affinic properties. Emphasis is on events at the fundamental molecular level.

Type of Paper: Review
Title: Elusive Neurotoxic Alkaloids: Saxitoxin and Its Analogues
Authors: Maria Wiese¹, Paul M. D’Agostino², Troco K. Mihali¹, Michelle C. Moffitt² and Brett A. Neilan¹
Affiliations: ¹ School of Biotechnology and Biomolecular Sciences, University of New South Wales, Australia
² School of Biomedical and Health Sciences, University of Western Sydney, Australia; E-Mail: P.D'Agostino@uws.edu.au (P.M.D.)
Abstract: Saxitoxin (STX) and its more than 45 analogues discovered to date are a broad group of natural toxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs). PSTs are the causative agents of paralytic shellfish poisoning (PSP) and are mostly associated with marine dinoflagellates (Eukaryotes) and freshwater cyanobacteria (Prokaryotes), which form extensive blooms around the world. Saxitoxin and its analogues can be structurally classified into several classes such as non-sulphated, mono-sulphated, di-sulphated, decarbamoylated and the recently discovered hydrophobic analogues. The neurotoxic effect of STX and derivatives in vertebrates is well known, however, a comprehensive understanding of their intracellular and extracellular biological role is still outstanding. The recent discovery of the saxitoxin biosynthesis pathway in several cyanobacteria has opened up the possibility of genetic studies to elucidate the biological function, phylogeny and molecular diversity of the PSTs and may possibly result in new candidate pharmacological leads.