Daisuke Uemura

ISOLATION AND STRUCTURE OF PINNATOXIN D, A NEW SHELLFISH POISON FROM THE OKINAWAN BIVALVE PINNA MURICATA

Abstract A new shellfish poison, pinnatoxin D, has been isolated from the Okinawan bivalve Pinna muricata . The planar structure was elucidated by extensive 2D NMR experiments, and the relative stereochemistry was deduced by NOESY data and 3 J HH coupling constants. Pinnatoxin D is a novel amphoteric carbocyclic compound which is composed of a 6,7-spiro ring, a 5,6-bicyclo ring and a 6,5,6-trispiro ketal involving 15 chiral centers.

Pinnaic acid and tauropinnaic acid: Two novel fatty acids composing a 6-azaspiro[4.5]decane unit from the Okinawan bivalve Pinna muricata

Abstract Two novel fatty acids with cPLA 2 inhibitory activity, pinnaic acid and tauro-pinnaic acid, were isolated from the Okinawan bivalve Pinna muricata . Their structures, including the relative stereochemistry at C5, C9, C13 and C14, were elucidated by extensive 2D NMR spectroscopic analysis.

Relative stereochemistry of pinnatoxin A, a potent shellfish poison from Pinna muricata

Abstract Pinnatoxin A, the principal toxin isolated from Pinna muricata , is a novel amphoteric macrocyclic compound composed of a 6,7-spiro ring, a 5,6-bicyclo ring and a 6,5,6-trispiroketal ring involving 14 chiral centers. The relative stereochemistry was deduced based on detailed analysis of NOESY and ROESY data, and 3 J HH coupling constants.

Structure of oxazolomycin, a novel β-lactone antibiotic

Abstract The structure of oxazolomycin exhibiting antitumor activity has been elucidated.

Studies on palytoxins

Abstract The complete structure of palytoxin ( 1 ) was elucidated by us in 1982. 1 Our continuous interests in palytoxin led us to examine minor constituents of Okinawan Palythoa tuberculosa . In this paper, we describe successful isolation and structural elucidation of four minor toxins, which were named homopalytoxin ( 2 ), bishomopalytoxin ( 3 ), neopalytoxin ( 4 ) and deoxypalytoxin ( 5 ).

Absolute stereochemistry of halichlorine; A potent inhibitor of VCAM-1 induction

Abstract The absolute stereochemistry of a marine alkaloid halichlorine, which significantly inhibits VCAM-1 induction in HUVE cells, was established by synthesis of a degradation product of natural product.

Further studies on palytoxin. I.

Abstract The structures of two degradation products of N-(p-bromobenzoyl) palytoxin were elucidated, and then the sequences of those fragments were determined.

Single ionic channels induced by palytoxin in guinea-pig ventricular myocytes.

1 Mechanisms of palytoxin‐induced ion permeability were examined in isolated single ventricular cells of guinea‐pig under whole‐cell‐attached patch clamp conditions. 2 Palytoxin (1–2 × 10−11 m, dissolved in Tyrode solution and put in the patch electrode) induced an elementary current flowing through single channels. Direction of the current was inward and the amplitude was 0.65 ± 0.03 pA (mean ± s.e. mean) at the resting membrane potential. The amplitude increased linearly with membrane hyperpolarization and decreased with depolarization; the single channel conductance was 9.5 ± 0.5 pS. 3 Palytoxin‐induced single channel current was resistant to tetrodotoxin (5 × 10−5 m) or cobalt ions (2 × 10−3 m) and was observed under Ca‐free conditions. However, no channel current was induced by palytoxin (10−11‐10−9 m) dissolved in Na+‐free, choline‐Tyrode solution. 4 Palytoxin also induced single channel currents in Na+‐free, NH+4‐, Li+‐ or Cs+‐Tyrode solution, and the slope conductances were 16.5 ± 1.6 pS, 9.2 ± 0.7 pS and 11.0 ± 0.7 pS, respectively. 5 These results indicate that palytoxin forms a new type of ionic channel with unique ion selectivity and gating behaviour.

Inhibitory effect of a toxin okadaic acid, isolated from the black sponge on smooth muscle and platelets.

1 Effects of okadaic acid, a toxin isolated from marine sponges, on smooth muscle contraction and platelet activation were examined. 2 Contractions in rabbit aorta induced by high concentrations of K+ and noradrenaline were inhibited by 0.1–1 μm okadaic acid in a concentration‐dependent manner. Spontaneous rhythmic contractions as well as high K+‐induced contraction in guinea‐pig taenia caeci were also inhibited by 1 μm okadaic acid. 3 High K+‐induced contraction in rabbit aorta was accompanied by increased Ca2+ influx measured with 45Ca2+ and increased cytosolic Ca2+ ([Ca2+]cyt) measured with fura‐2‐Ca2+ fluorescence. Okadaic acid inhibited the contraction without inhibiting Ca2+ influx and produced only a small decrease in [Ca2+]cyt. 4 In a saponin‐skinned taenia, Ca2+‐induced contraction was not inhibited but rather potentiated by okadaic acid. 5 Okadaic acid, 1 μm, inhibited aggregation, ATP release and increase in [Ca2+]cyt induced by thrombin in washed rabbit platelets. Okadaic acid itself did not change the platelet activities. 6 Okadaic acid did not change the cyclic AMP content of rabbit aorta although the inhibitory effects of okadaic acid were similar to those of cyclic AMP. 7 Although the mechanism of the inhibitory effect of okadaic acid was not clarified in the present experiments, it is suggested that okadaic acid acts by inhibiting protein phosphatases resulting in an indirect activation of cyclic AMP‐dependent protein phosphorylation.

ABSOLUTE CONFIGURATION OF NORZOANTHAMINE, A PROMISING CANDIDATE FOR AN OSTEOPOROTIC DRUG

Abstract The absolute configuration of norzoanthamine ( 1 ) was determined to be 2 R 4 S , 6 S , 9 S , 10 R , 12 S , 13 R , 18 S , 21 S , and 22 S based on 1 H NMR spectral data of the MTPA esters of norzoamthamine derivatives. The possible biogenesis of zoanthamines is also proposed.