Charles W. Jefford

Manzamine B and C, two novel alkaloids from the sponge haliclona sp.

Abstract The title compounds were isolated from a marine sponge collected off Okinawa. Their structures were determined by X-ray and shown to be 1-β-carbolines. Manzamine C was the 2-ethyl-N-azacycloundec-6-ene derivative, whereas manzamine B was more complex being the epoxy isomer of the free base of dihydromanzamine A.

Why artemisinin and certain synthetic peroxides are potent antimalarials. Implications for the mode of action.

The discovery that the sesquiterpene peroxide yingzhaosu A (13) and 1,2,4-trioxane artemisinin (14) are active against chloroquine-resistant strains of Plasmodium falciparum, has opened a new era in the chemotherapy of malaria. In vitro and in vivo tests with synthetic structurally simpler trioxanes clearly demonstrate that much of the skeleton of 14 is redundant and that chirality is not required for activity. In addition, structure-activity relations and the search for the pharmacophore reveal that high antimalarial activity can be displayed by molecules which do not resemble the geometry of 13 and 14 at all. The possible mode of action of 13, 14, and synthetic peroxides is examined. They are believed to kill intraerythrocytic Plasmodium by interacting with the heme discarded by proteolysis of ingested hemoglobin. Complexation of heme with the peroxide bond followed by electron transfer generates an oxy radical that evolves to the ultimate parasiticidal agent. Experiments with ferrous reagents indicate that active peroxides including 14 and its congeners kill the parasite by alkylation with a sterically non-encumbered C-centered radical. However, another possibility is the involvement of a Fe(IV)=O species as the toxic agent. The review covers our own and other contributions to this timely topic and evaluates the different mechanisms proposed for the mode of action of peroxidic antimalarials.

Venustatriol. A new, anti-viral, triterpene tetracyclic ether from Laurencia venusta

Abstract Venustatriol, a new tetracyclic ether derived from squalene, which has anti-viral activity, has been isolated from the red alga Laurencia venusta . Its structure and absolute configuration were determined by X-ray using the absolute structure parameter x. By comparison of their spectral properties, the absolute configuration of its congener, thyrsiferol, was deduced.

Structures and absolute configurations of the marine toxins, latrunculin A and laulimalide

Abstract Latrunculin A ( 1 ) and laulimalide ( 2 ) were isolated from Fasciospongia rimosa collected in Okinawan waters. By purification, single crystals were obtained thereby enabling the absolute configurations of 1 and 2 to be determined by X-ray analysis.

Second-generation antimalarial endoperoxides

Artemisinin, derived from a Chinese herbal remedy, is a potent peroxide-containing antimalarial. New types of peroxides, derived from this structure, as well as other naturally occurring antimalarial peroxides, have been synthesized and found to have potent antimalarial activities. Studies on the activities, modes of action, and toxicities of these compounds are discussed here by Steven Meshnick and colleagues.

Diastereoselectivity in the directed aldol condensation of 2-trimethylsiloxyfuran with aldehydes. A stereodivergent route to threo and erythro δ-hydroxy-γ-lactones

Abstract Threo and erythro -δ-hydroxy-α,β-unsaturated γ-lactones are obtained with useful diastereoselection by condensing 2-trimethylsiloxyfuran and aldehydes by varying the reaction reaction conditions. A stereomechanistic rationale is presented together with a practical two-step synthesis of the threo and erythro 5-hydroxy-4-decanolides (L factors).

Batzellines A, B, and C. Novel pyrroloquinoline alkaloids from the sponge Batzella Sp.

Three highly functionalized pyrroloquinoline alkaloids, batzelline A ( 1 ), B ( 2 ), and C ( 3 ) were isolated from the deep water Bahamas sponge Batzella sp. The structure of 1 was determined by X-ray and those of 2 and 3 deduced by comparison of their spectral data with that of 1 and by chemical transformations.

An enantiospecific synthesis of solenopsin A

Enantiomerically pure solenopsin A (1) was prepared in 11 steps from L-aspartic acid (3) in an overall yield of 17%. 6R-(N-tosylamino)heptadecan-2-one (8), prepared from 3, underwent cyclization on acid catalysis to N-tosylamino-2,3-dehydro-2-methyl-6R-undecylpiperidine (9), which on reduction and deprotection gave 1.

Enantiospecific syntheses of indolizidines 167B and 209D

Abstract Indolizidine 209D ( 2 ) was synthesized in 11 steps from L-aspartic acid ( 3 ) in an overall yield of 16%. 3R-pyrrolylnonanoic acid, prepared from 3 , was converted into the α-keto diazomethyl derivative, which on Rh 2 (OAc) 4 -catalyzed cyclization and catalytic hydrogenation gave 2 . A similar procedure, starting from 3 , afforded 3R-pyrrolylhexanoic acid, an intermediate which had previously been converted in 3 steps to indolizidine 167B.

A New Method for the Synthesis of gem-Dihydroperoxides

The tungstic acid-catalyzed reaction of ketals with hydrogen peroxide provides a convenient and efficient method for preparing gem-dihydroperoxides.