At otal synthesis of prunustatin A, aG RP78 molecular chaperone down-regulator,h as been achieved. The key step in the synthesis is an intramolecular transesterification of the b-keto ester alcohol intermediate to construct the 15-membered tetralactone core of the natural product.Microbial species have the capability to produce aw ide variety of bioactive compounds with previously unknown structures and variousb iological activities. Prunustatin A( 1,F igure 1), a1 5-memberedt etralactone antibiotic with a3 -formamidosalicylic moiety first isolatedi n2 005 by Shin-ya and co-workers from as train of Streptomycesv iolaceoniger 4521-SVS3, showed inhibitory activity against GRP78 expression inducedb y2 -deoxyglucose stimulationi nH T1080 cells.[1] Subsequents tudies established that the tetralactone moiety is made up of four subunits,( 4 S)-2,2-dimethyl-4-hydroxy-3-oxo-5-phenylpentanoic acid, (S)-lactic acid, l-threonine, and (2S,3S)-2-hydroxy-3-methylpentanoic acid, as shown in Figure 1.[2] Prunustatin A( 1)i s similar in structure to SW-163A (2) [3] and neoantimycin (3). [4] neoantimycin (3)i sarare and unusualr ing-extended member of the antimycin class. The recent discoveryo f1 as as elective GRP78 molecular chaperone down-regulator,w hichc ould lead to the development of new approaches towards treating cancer,h ighlights the potential of this class as research probes.Antimycin A 3 ,o ne of the first knowna nd most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc 1 complex. Since UK-2A, an antimycin-class antibiotic, was first isolatedi n1 996 from as oil sample collecteda to ur campus by Shibata, Ta niguchi and co-workers, [5] we have been attempting to establish the structure-activity relationshipsa mong antimycin A 3 and UK-2A (Figure 2).[6] As an extension of our research, we have been engaged in studies towardt he synthesis and biological evaluation of 1.Herein, we report atotal synthesis of prunustatin A( 1).Our initial access to construct the tetralactone core of 1 was based on an intramolecular Mitsunobu reaction of 4 as previously reported (Scheme 1), [7] where we have developedt he CÀ Cb ond formation reactionb etween C1 and C11v ia Reformatsky reaction. However,a ll attempts at cyclizationsb etween O2 and C2 via intramolecular Mitsunobu reaction and other lactonization procedures resulted in the formation of undesired five-membered lactones.T his would be caused by the gem-dimethylg roups at C11.Recently,t he first total synthesis of 1 was reported, [8] where cyclized point was selected at O4 and C5 by conformational Scheme1.Our initial access to construct the tetralactone core of 1.Boc = tert-butyloxycarbonyl.[ analysisa nd molecular dynamics. With these results in mind, we embarkedo nanew synthetic strategy towards 1 that involved cyclization via transesterification of b-keto ester 8 followed by introduction of the gem-dimethyl groups at C11 (Scheme2). Conceptually,r ing-closure precursor 8 would be prepared by condensat...

To predict PEFC performance without complicated simulation or a lot of experimental data is required for the optimum design of the cell, especially the cathode catalyst layer (CCL). In our previous study, the effectiveness factor of CCL was reported to be a function solely of 4 dimensionless moduli which were derived from the isothermal one-dimensional model of the cathode consisting of oxygen balance, oxygen transport, proton transport, reaction stoichiometry, and rate. In this study, the dependency of the oxygen reduction reaction (ORR) rate on CCL thickness is analyzed and a method to determine dimensionless moduli is proposed.

The first total synthesis of neoantimycin (1), an unusual ring-extended antibiotic of the antimycin class, has been achieved, using intramolecular transesterification for construction of the 15-membered tetralactone core.

For widespread use of polymer electrolyte fuel cell (PEFC), it is necessary to reduce the amount of platinum by optimizing the cathode catalyst layer (CCL) structure. Therefore, oxygen reduction reaction (ORR) rate which does not include the mass transfer resistance in CCL should be formulated. To measure the ORR rate which does not include the mass transfer resistance in the CCL, a thin layer electrode was prepared by directly sputtering platinum to microporous layer (MPL) on gas diffusion layer. Dependencies of ORR rate on temperature and relative humidity (RH), were measured and analyzed. From the measurement results, ORR parameters which do not include the effect of mass transfer resistance through the CCL were appropriately determined. The ORR rate and electrochemical surface area (ECSA) depend on RH and a half of RH dependency of ORR rate is ascribed to change in ECSA.

The first total syntheses of JBIR-06 and two analogous depsipeptides, 12-membered antimycin-class antibiotics, have been accomplished via Shiina macrolactonization. Comparison of the spectroscopic data of the synthesized compounds with those reported for natural products verified that the absolute configutation of the natural products was (2S, 4S, 6S, 7R, 14S).