Yasuji Yamada

Antimalarial activity of kalihinol A and new relative diterpenoids from the Okinawan sponge, Acanthella sp.

Abstract Three new kalihinane diterpenoids Δ9-kalihinol Y (1), 10-epikalihinol I (2) and 5,10-bisisothiocyanatokalihinol G (3) were isolated in the present study along with previously detected kalihinane diterpenoids kalihinol A (4), kalihinene (5) and 6-hydroxykalihinene (6) from the Okinawan marine sponge, Acanthella sp. Kalihinol A (4) was noted to possess remarkable in vitro antimalarial activity.

Total synthesis of phomactin D

A total synthesis of (+/-)-phomactin A is described to highlight the final completion of a complex natural product target that had commenced with an intramolecular oxa-[3 + 3] annulation strategy in the construction of the ABD-tricycle. These efforts reveal structural intricacies of this ABD-tricycle with an illustrative example being the conformational analysis that was ultimately critical for the C5a-homolgation.

Identification of a new eicosanoid from in vitro biosynthetic experiments with Clavularia viridis. Implications for the biosynthesis of clavulones

Abstract A cell-free homogenate of Clavularia viridis converts tritiated arachidonic acid into a new eicosanoid identified as 4 (free acid) by chemical and chromatographic studies in comparison with synthetic substances. The isolation of 4 suggests a novel, non-prostanoid type pathway for the biosynthesis of the clavulones.

Aragusterols E-H, new 26,27-cyclosterols from the Okinawan marine sponge of the genus Xestospongia and absolute configurations of xestokerols A and B

Abstract New 26, 27-cyclosterols, aragusterols E-H, were isolated from the Okinawan marine sponge of the genus Xestospongia . Their structures were determined by spectroscopic measurement and chemical conversion. The absolute configurations of xestokerols A and B were determined by chemical conversion.

Samarium(II) iodide-induced tandem reductive coupling-Dieckmann condensation reaction: one-step synthesis of bicyclic oxacyclopentanecarboxylate from bis-α,β-unsaturated esters

Abstract The tandem cyclization of bis-α,β-unsaturated esters with SmI 2 -Sm–THF in the presence of catalytic amount of methanol was found to stereoselectively provide bicyclo[4.3.0]nonan-8-ones and bicyclo[3.3.0]octan-3-ones.

Synthesis of marine sesterterpenoid dysidiolide

Abstract Dysidiolide, a novel sesterterpenoid isolated from the Caribbean sponge Dysidia etheria de Laubenfels, has been shown an inhibitor of protein phosphatase cdc25A. The authors established a stereocontrolled total synthesis of (±)-dysidiolide using an intramolecular Diels–Alder reaction as the key step.

Mechanism of action of aragusterol a (YTA0040), a potent anti-tumor marine steroid targeting the G1 phase of the cell cycle

Aragusterol A (YTA0040), isolated from the Okinawan marine sponge of the genus Xestospongia, is a potent anti‐tumor marine steroid that possesses a unique structural component. This compound showed broad‐spectrum anti‐proliferative activity against a panel of 14 human cancer cell lines (IC50 = 0.01–1.6 μM). P‐glycoprotein–mediated, multidrug‐resistant cells showed cross‐resistance to YTA0040 cells, whereas cisplatin‐resistant non‐small‐cell lung‐cancer (NSCLC) sublines showed a collateral sensitivity to YTA0040. In transplantable murine tumor models, YTA0040 displayed a broad spectrum and high degree of anti‐tumor activity when administered i.p. or p.o. (life span T/C = 135–234%). In P388 murine leukemia cells, YTA0040 caused dose‐ and time‐dependent suppression of nucleic acid and protein synthesis, with protein synthesis being more potently and rapidly inhibited than nucleic acid synthesis. Flow‐cytometric analysis revealed that YTA0040 blocked the entry of human NSCLC‐derived A549 cells into S phase, leading to arrest in the G1 phase of the cell cycle. Western blot analysis demonstrated that YTA0040 caused a dose‐dependent decrease in the levels of expression of hyperphosphorylated pRb and cyclin A in A549 cells. The level of p53 protein expression was decreased by YTA0040 treatment. A higher concentration of YTA0040 down‐regulated the levels of expression of CDK2, CDK4, cyclin D1 and cyclin E. These findings indicated that YTA0040 arrested human NSCLC cells in late G1 phase of the cell cycle through inhibition of pRb phosphorylation. Inhibition of pRb phosphorylation by YTA0040 resulted from down‐regulation of levels of expression of the CDKs and cyclins involved in the G1/S transition and not from induction of p53 and/or the CDK inhibitor p21. Int. J. Cancer 88:810–819, 2000.

TOTAL SYNTHESIS OF DOLABELLANE DITERPENOID CLAENONE

Abstract Marine dolabellane diterpenoid claenone ( 1 ) was synthesized from D-mannitol. This synthesis involves the formation of bicyclo[2.2.1]heptane derivative 4a by sequential Michael reaction, the formation of cyclopentane derivative 9 by retro-aldol reaction and the cyclization of sulfone 19 .

Total synthesis of marine diterpenoid stolonidiol

Abstract Marine dolabellane diterpenoid stolonidiol was synthesized from l -ascorbic acid. The method for this total synthesis involves formation of the bicyclo[2.2.1]heptane derivative using a diastereoselective sequential Michael reaction, formation of cyclopentane derivative by the retro-aldol reaction and construction of an 11-membered carbocyclic ring through the intramolecular Horner–Wadsworth–Emmons reaction.

Total Synthesis of Marine Oxylipin Bacillariolides I–III

Abstract Marine oxylipin bacillariolides I–III were synthesized from (R)-malic acid, using diastereoselective one-pot formation of the chiral cyclopentane derivative from the anion of allyl phenyl sulfone and chiral epoxymesylate as the key reaction.