The potential of the marine environment to produce candidate compounds (structures) as leads to, or even direct drugs from, has been actively discussed for the last 50 or so years. Over this time frame, several compounds have led to drugs, usually in the area of cancer (due to funding sources). This review is designed to show where there have been successes, but also to show that in a number of disease areas, there are structures originally isolated from marine invertebrates and free-living microbes that have potential, but will need to be "adopted" by pharmaceutical houses in order to maximize their potential.

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Drugs and Drug Candidates from Marine Sources: An Assessment of the Current "State of Play"

Saponine stellen Naturstoffe dar, die durch eine Reihe gemeinsamer Eigenschaften gekennzeichnet sind. Als erstes Charakteristikum wurde das starke Schaumvermogen in wasriger Losung bemerkt, das dieser Gruppe den Namen gegeben hat. Weitere Eigenschaften sind die hamolytische Aktivitat, die Toxizitat fur Fische, die Cholesterin- komplexbildung und, neuerdings beobachtet, eine antibiotische Aktivitat, vornehmlich gegen niedere Pilze.

Chemie und Biologie der Saponine

The reductive cleavage of the ether bridge of 5α-chloro- and 5α-bromo-6β, 19-oxido-steroids to 19-hydroxy-Δ5-steroids has been studied : Whereas 5α-bromo-6β, 19-ethers could be reduced under mild conditions, i. e. with zinc and acetic acid, 5α-chloro-6β, 19-ethers could only be cleaved with lithium and liquid ammonia. However, the latter steroids with an additional electronegative substituent in 19-position, namely 5α-chloro-6β, 19-hemiacetals and -lactones, were smoothly converted into Δ5-19-aldehydes and Δ5-19-acids, respectively, by the action of zinc and acetic acid. The Δ5-steroid-3 9-oic acids obtained could be decarboxylated thermally to Δ5(10)-19-norsteroids.

19‐Norsteroide IV. Über die reduktive Ätherspaltung bei 5α‐Halogen‐6β, 19‐oxido‐steroiden. Über Steroide, 198. Mitteilung

One Pot Phase Transfer Synthesis of Trithiocarbonates from Carbon Bisulphide and Alkyl Halides

Nicotinic acetylcholine receptors (nAChRs) are members of the cys-loop superfamily of ligand-gated ion channels (cys-loop LGICs) and mediate fast cholinergic synaptic transmission in the nervous system of insects. The completion of many insect genome projects has greatly enhanced our understanding of the individual subunits that make up nAChR gene families from an insect genetic model organism (Drosophila melanogaster), crop pests, disease vectors and beneficial (pollinator) species. In addition to considerable insect nAChR subunit diversity, individual subunits can be subject to alternative splicing and RNA editing and these post-transcriptional modifications can add significantly to the diversity of nAChR receptor subtypes. The actions of insecticides targeting nAChRs, notably cartap, neonicotinoids, sulfoximines, flupyradifurone, spinosyns and triflumezopyrim are reviewed. Structural studies obtained using an acetylcholine binding protein (AChBP) co-crystallised with neonicotinoids have yielded important new insights into the requirements for neonicotinoid insecticide – nAChR interactions. The persistent application of insecticides to crop pests leads to the onset of resistance and several examples of resistance to insecticides targeting nAChRs have been documented. Understanding the molecular basis of resistance can inform our understanding of the mechanism of insecticide action. It also provides an important driver for the development of new chemistry, diagnostic tests for resistance and the adoption of application strategies designed to attenuate such problems. Finally, we consider toxicity issues relating to nAChR-active insecticides, with particular reference to beneficial insect species (pollinators) as well as mammalian and avian toxicity. This review is part of the special issue "Insecticide Mode of Action: From Insect to Mammalian Toxicity"

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Modes of Action, Resistance and Toxicity of Insecticides Targeting Nicotinic Acetylcholine Receptors.

Syntheses of 19-Nor-3-ketosteroids

An improved synthesis of nereistoxin (VII or XIII ; R3=CH3) was achieved via the intermediates VIII (R3=CH3), X (R3=CH3) and XII (R3=CH3) as summarized in Chart 2. Applying the reactions formulated in Chart 1 and Chart 2, a number of amines were prepared, whereby the occurrence of intermediates, cyclic sulfonium (III) in the amination reaction in Chart 1 and cyclic immonium (IX) in the thiolation reaction in Chart 2 respectively, was suggested.

Synthesis of nereistoxin and related compounds. i.

Oxidation of steroids by microörganisms; 19-hydroxylation of Reichstein's compound S by Corticium sasakii.

Compounds of the formula WHEREIN R represents a lower alkoxy-thiocarbonyl group and A represents a tertiary amino group are useful as pesticides.

Hikoichi Hagiwara

Papers

Syntheses of 19-Nor-3-ketosteroids

Synthesis of nereistoxin and related compounds. i.

Oxidation of steroids by microörganisms; 19-hydroxylation of Reichstein's compound S by Corticium sasakii.

Dithio amino alkanes

Steroids. II: Tokorogenin, a New Sapogenin Isolated from Dioscorea tokoro @@@オニドコロの新サポゲニン“トコロゲニン”について