Eiseniachloride B is a marine chlorinated oxylipin isolated from the brown alga Eisenia bicyclis. This natural product contains cyclopentane, chlorohydrin, and 14-membered lactone systems that incorporate five stereogenic centers. In this paper, we report on the total synthesis of structurally unique oxylipin eiseniachloride B from optically active lactol via ecklonialactone B in a linear sequence comprising 11 steps with a 12.1% overall yield.The addition of an aqueous solution of diketopiperazine cyclo(Pro-Xxx) (Xxx amino acid residue) to an aqueous solution of (-)-epigallocatechin-3-O-gallate (EGCg) led to precipitation of the complex of EGCg and cyclo(Pro-Xxx). The molecular capture abilities of cyclo(Pro-Xxx) using EGCg were evaluated by the ratio of the amount of cyclo(Pro-Xxx) included in the precipitates of the complex with EGCg to that of the total cyclo(Pro-Xxx) used. Stronger hydrophobicity of the side chain of the amino acid residue of cyclo(Pro-Xxx) led to a higher molecular capture ability. Furthermore, the molecular capture ability decreased when the side chain of the amino acid residue had a hydrophilic hydroxyl group. When diketopiperazine cyclo(Pro-Xxx), excluding cyclo(D-Pro-L-Ala), was taken into the hydrophobic space formed by the three aromatic A, B, and B' rings of EGCg, and formed a complex, their conformation was maintained in the hydrophobic space. Based on nuclear Overhauser effect (NOE) measurement, the 3-position methyl group of cyclo(D-Pro-L-Ala) in D2O was axial, whereas that of cyclo(L-Pro-L-Ala) was equatorial. When cyclo(D-Pro-L-Ala) was taken into the hydrophobic space of EGCg and formed a 2  2 complex, its 3-position methyl group changed from the axial position to the equatorial position due to steric hindrance by EGCg.Novel derivatives of puberulic acid were synthesized and their antimalarial properties were evaluated in vitro against the Plasmodium falciparum K1 parasite strain, cytotoxicity against a human diploid embryonic cell line MRC-5, and in vivo efficacy using a Plasmodium berghei-infected mouse model. From previous information that three hydroxy groups on the tropone framework were essential for antimalarial activity, we converted the carboxylic acid moiety into the corresponding esters, amides, and ketones. These derivatives showed antimalarial activity against chloroquine-resistant Plasmodium in vitro equivalent to puberulic acid. We identified that the pentane-3-yl ester, cyclohexyl ester, iso-butyl ketone, cyclohexyl methyl ketone all show an especially potent antiparasitic effect in vivo at an oral dose of 15 mg/kg without any apparent toxicity. These esters were more effective than the existing commonly used antimalarial drug, artesunate.Sperm activation is an essential process by which the male gametes become capable of fertilization. Because the process in Caenorhabditis elegans is readily reproducible in vitro, this organism serves as an excellent model to investigate it. C. elegans sperm activation in vivo occurs during spermiogenesis. Membranous organelles (MOs) contained within spermatids fuse with the plasma membrane, resulting in extracellular release of their contents and relocation of some proteins indispensable for fertilization from the MO membrane onto the sperm surface. Intriguingly, these cytological alternations are exhibited similarly in mouse spermatozoa during the acrosome reaction, which also represents a form of sperm activation, prompting us to hypothesize that C. elegans and mice share a common mechanism for sperm activation. To explore this, we first screened a chemical library to identify compounds that activate C. elegans spermatozoa. Because a quinolinol analog named DDI-6 seemed to be a candidate sperm activator, we synthesized it to use for further analyses. This involved direct dechlorination and hydrogenolysis of commercially available 5-chloro-8-quinolinol, both of which are key steps to yield 1,2,3,4-tetrahydro-8-quinolinol, and we subsequently introduced the sulfonamide group to the compound. selleck products When C. elegans spermatids were stimulated with solvent alone or the newly synthesized DDI-6, approx. 3% and approx. 28% of spermatids became MO-fused spermatozoa, respectively. Moreover, DDI-6 triggered the acrosome reaction in approx. 20% of mouse spermatozoa, while approx. 12% became acrosome-reacted after mock stimulation. Thus, DDI-6 serves as a moderately effective activator for both C. elegans and mouse spermatozoa.Soft sensors play a crucial role as process analytical technology (PAT) tools. They are classified into physical models, statistical models, and their hybrid models. In general, statistical models are better estimators than physical models. In this study, two types of standard statistical models using process parameters (PPs) and near-infrared spectroscopy (NIRS) were investigated in terms of prediction accuracy and development cost. Locally weighted partial least squares regression (LW-PLSR), a type of nonlinear regression method, was utilized. Development cost was defined as the cost of goods required to construct an accurate model of commercial-scale equipment. Eleven granulation lots consisting of three laboratory-scale, two pilot-scale, and six commercial-scale lots were prepared. Three commercial-scale granulation lots were selected as a validation dataset, and the remaining eight granulation lots were utilized as calibration datasets. The results demonstrated that the PP-based and NIRS-based LW-PLSR models achieved high prediction accuracy without using the commercial-scale data in the calibration dataset. This practical case study clarified that the construction of accurate LW-PLSR models requires the calibration samples with the following two features 1) located near the validation samples on the subspace spanned by principal components (PCs), and 2) having a wide range of variations in PC scores. In addition, it was confirmed that the reduction in cost and mass fraction of active pharmaceutical ingredient (API) made the PP-based models more cost-effective than the NIRS-based models. The present work supports to build accurate models efficiently and save the development cost of PAT.