Stellatolide H,a cytotoxic peptide lactone from a deep-sea sponge Discodermia sp.

Stellatolide H (1) was isolated from a deep-sea sponge Discodermia sp. as the cytotoxic constituent. The planar structure of 1 was elucidated on the basis of the NMR spectroscopic and mass spectrometric data. The absolute configurations of the constituent amino acid residues were determined by the Marfey’s method. Stellatolide H (1) is a peptide lactone of the callipeltin class with its N-terminus blocked by 3-hydroxy-6,8-dimethyldeca-(4Z,6E)-dienoic acid (Hdda).     

Total Synthesis of the Nonribosomal Peptide Surugamide B and Identification of a New Offloading Cyclase Family

The cathepsin B inhibitor surugamide B ( 2 ), along with structurally related derivatives (A and C–E), has previously been isolated from the marine actinomycete Streptomyces sp. JAMM992. The biosynthetic genes are unexpectedly part of a cluster of four non‐ribosomal peptide synthetase (NRPS) genes, two of which are responsible for the biosynthesis of the additional linear decapeptide surugamide F. However, the thioesterase domain required for the later stage of the biosynthesis of the cyclic peptides surugamides A–E is not present in any module architecture of the surugamide NRPSs. Herein, we report the first total synthesis of surugamide B ( 2 ) through the macrocyclization at the biomimetic position, which not only alleviated the Cα epimerization in the macrolactamization process, but also efficiently provided 2 in 34 % yield for 18 steps. Furthermore, both the chemical and enzymatic studies with the biosynthetic precursor mimics revealed that the stand‐alone enzyme SurE, which belongs to the penicillin‐binding protein family, is responsible for macrocyclization of the tethered octapeptidyl intermediate.     

Chiral Carboxylic Acid Enabled Achiral Rhodium(III)‐Catalyzed Enantioselective C−H Functionalization

Reported is an achiral Cp^xRh^III/chiral carboxylic acid catalyzed asymmetric C?H alkylation of diarylmethanamines with a diazomalonate, followed by cyclization and decarboxylation to afford 1,4‐dihydroisoquinolin‐3(2H)‐one. Secondary alkylamines as well as nonprotected primary alkylamines underwent the transformation with high enantioselectivities (up to 98.5:1.5 e.r.) by using a newly developed chiral carboxylic acid as the sole source of chirality to achieve enantioselective C?H cleavage by a concerted metalation‐deprotonation mechanism.     

DNA Origami Scaffolds as Templates for Functional Tetrameric Kir3 K+ Channels

In native systems, scaffolding proteins play important roles in assembling proteins into complexes to transduce signals. This concept is yet to be applied to the assembly of functional transmembrane protein complexes in artificial systems. To address this issue, DNA origami has the potential to serve as scaffolds that arrange proteins at specific positions in complexes. Herein, we report that Kir3 K⁺ channel proteins are assembled through zinc‐finger protein (ZFP)‐adaptors at specific locations on DNA origami scaffolds. Specific binding of the ZFP‐fused Kir3 channels and ZFP‐based adaptors on DNA origami were confirmed by atomic force microscopy and gel electrophoresis. Furthermore, the DNA origami with ZFP binding sites nearly tripled the K⁺ channel current activity elicited by heterotetrameric Kir3 channels in HEK293T cells. Thus, our method provides a useful template to control the oligomerization states of membrane protein complexes in vitro and in living cells.     

Direct catalytic asymmetric Mannich-type reaction of beta-keto phosphonate using a dinuclear Ni2-Schiff base complex

Direct catalytic asymmetric Mannich-type reactions of beta-keto phosphonates are described. A homodinuclear Ni 2-Schiff base complex promoted the reaction at 0 degrees C, giving beta-amino phosphonates in up to 90% yield, 20:1 dr, and 99% ee. Control experiments suggested that two Ni metals are important for achieving high yield and stereoselectivity.     

Koshikamide B, a cytotoxic peptide lactone from a marine sponge Theonella sp

Koshikamide B (1) has been isolated from two separate collections of the marine sponge Theonella sp. as the major cytotoxic constituent. Koshikamide B is a 17-residue peptide lactone composed of six proteinogenic amino acids, two D-isomers of proteinogenic amino acids, seven N-methylated amino acids, and two unusual amino acid residues. The unusual amino acids are N(delta)-carbamoylasparagine and 2-(3-amino-2-hydroxy-5-oxopyrrolidin-2-yl)propionic acid (AHPP); the former is first found as the constituent of peptides, whereas the latter is a new amino acid residue. The N-terminus of koshikamide B is blocked by a methoxyacetyl group. The structure of koshikamide B (1) has been determined by interpretation of spectral data and analysis of chemical degradation products. Koshikamide B (1) exhibits cytotoxicity against P388 murine leukemia cells and the human colon tumor (HCT-116) cell line with an IC50 value of 0.45 and 7.5 microg/mL, respectively.     

Water properties in the super-salt-resistive gel probed by NMR and DSC

The so-called "super-salt-resistive gel", or poly(4-vinylphenol) (P4VPh) hydrogel, of different water contents ( H = 97-51%) was prepared by cross-linking with different amounts of ethylene glycol diglycidyl ether. 1H NMR spectroscopy was used to investigate the dynamic properties of water in the gel samples in terms of the spin-spin relaxation. The T2 values in those hydrogels were analyzed by assuming a two-component system, namely, T 2(long) and T2(short), and their fractions were obtained. In the higher water content region (75% < or = H < or = 97%), T2(long) for P4VPh gel was almost constant or even slightly increased with decreasing temperature. On the other hand, T2(long) for poly(vinyl alcohol) (PVA) gel (80% < or = H < or = 96%) significantly decreased with decreasing temperature, showing a natural behavior for water mobility in common hydrogels. Water in P4VPh gels of lower water contents ( H = 70% and 51%) also showed intriguing behaviors: the T2 values are much larger than those of gels with higher water contents and decreased with decreasing temperature only in the lower temperature range (<10 degrees C). The fraction of T2(long) values of P4VPh gel showed another contrast to those of PVA gel; the latter decreased with decreasing water content (normal behavior), while in the former gel the highest fraction (ca. 60% at 20 degrees C) was observed for a sample with the lowest water content ( H = 51%). On the other hand, the results of DSC measurements for P4VPh gel were less specific than those of T2 and comparable to those of common hydrogels such as PVA; with decreasing water content, the total amounts of free water and freezable bound water per polymer mass (g/g) decreased, while the amount of nonfreezing water per polymer also decreased.     

Ligand-free Sonogashira coupling reactions with heterogeneous Pd/C as the catalyst

A variety of aryl iodides were coupled with aromatic and aliphatic terminal alkynes to give the corresponding 1,2-disubstituted aromatic alkynes in good yields by using only 0.4 mol % of the heterogeneous 10 % Pd/C as the catalyst without a ligand, copper salt, or amine in an aqueous medium.     

Synthesis, structures, and properties of group 9- and group 10-group 6 heterodinuclear nitrosyl complexes

The reaction of the group 9 bis(hydrosulfido) complexes [Cp*M(SH)2(PMe3)] (M=Rh, Ir; Cp*=eta(5)-C 5Me5) with the group 6 nitrosyl complexes [Cp*M'Cl2(NO)] (M'=Mo, W) in the presence of NEt3 affords a series of bis(sulfido)-bridged early-late heterobimetallic (ELHB) complexes [Cp*M(PMe3)(mu-S)2M'(NO)Cp*] (2a, M=Rh, M'=Mo; 2b, M=Rh, M'=W; 3a, M=Ir, M'=Mo; 3b, M=Ir, M'=W). Similar reactions of the group 10 bis(hydrosulfido) complexes [M(SH)2(dppe)] (M=Pd, Pt; dppe=Ph 2P(CH2) 2PPh2), [Pt(SH)2(dppp)] (dppp=Ph2P(CH2) 3PPh2), and [M(SH)2(dpmb)] (dpmb=o-C6H4(CH2PPh2)2) give the group 10-group 6 ELHB complexes [(dppe)M(mu-S)2M'(NO)Cp*] (M=Pd, Pt; M'=Mo, W), [(dppp)Pt(mu-S)2M'(NO)Cp*] (6a, M'=Mo; 6b, M'=W), and [(dpmb)M(mu-S)2M'(NO)Cp*] (M=Pd, Pt; M'=Mo, W), respectively. Cyclic voltammetric measurements reveal that these ELHB complexes undergo reversible one-electron oxidation at the group 6 metal center, which is consistent with isolation of the single-electron oxidation products [Cp*M(PMe3)(mu-S)2M'(NO)Cp*][PF6] (M=Rh, Ir; M'=Mo, W). Upon treatment of 2b and 3b with ROTf (R=Me, Et; OTf=OSO 2CF 3), the O atom of the terminal nitrosyl ligand is readily alkylated to form the alkoxyimido complexes such as [Cp*Rh(PMe3)(mu-S)2W(NOMe)Cp*][OTf]. In contrast, methylation of the Rh-, Ir-, and Pt-Mo complexes 2a, 3a, and 6a results in S-methylation, giving the methanethiolato complexes [Cp*M(PMe3)(mu-SMe)(mu-S)Mo(NO)Cp*][BPh 4] (M=Rh, Ir) and [(dppp)Pt(mu-SMe)(mu-S)Mo(NO)Cp*][OTf], respectively. The Pt-W complex 6b undergoes either S- or O-methylation to form a mixture of [(dppp)Pt(mu-SMe)(mu-S)W(NO)Cp*][OTf] and [(dppp)Pt(mu-S) 2W(NOMe)Cp*][OTf]. These observations indicate that O-alkylation and one-electron oxidation of the dinuclear nitrosyl complexes are facilitated by a common effect, i.e., donation of electrons from the group 9 or 10 metal center, where the group 9 metals behave as the more effective electron donor.