Enzymatic synthesis of flavin adenine dinucleotide

A new and simple enzymatic method for the synthesis of flavin adenine dinucleotide (FAD) from flavin mononucleotide by the transadenylylation reaction using microbial cells is described. Among various microorganisms tested,Artherobacter globiformis IFO 12138 and two soil bacteria were selected as useful enzyme sources. Under suitable reaction conditions, the amount of FAD synthesized was 2.25 μmol/mL with cells ofA. globiformis. The transadenylylation reaction could be coupled with the ATP supplying system through a glycolysis process with yeast.     

An asymmetric synthesis of α-tocopherol side chain

A stereospecific synthesis of (3R,7R)?3,7,11-trimethyldodecanal (2) with highly optical purity was achieved by utilizing the coupling reaction of the amino sulfone (9) with(R)?3,7-dimethyloctyl magnesium bromide (7), and the asymmetric isomerization of the resulting(E)-allylic amine (10).     

A package compound of a metal atom with a hydrocarbon [4][4][4][4][3](1,2,3,4,5)ferrocenophane

Perbridged ferrocenes ($\text{9}$ and $\text{11}$: the title compound) have been synthesized and characterized by spectroscopies and X-ray diffraction, and an interesting rotational disorder has been found by the X-ray crystal analyses of both $\text{9}$ and $\text{11}$.     

Giant meso-meso-linked porphyrin arrays of micrometer molecular length and their fabrication

On the basis of the Ag(I)-promoted coupling reaction of zinc(II)-5,15-bis(3,5-dioctyloxyphenyl)porphyrin Z1, chain elongation has been attempted by using a stepwise doubling approach, which provides Z2, Z4, Z8, Z16, Z32, Z64, Z128, Z256, Z384, and Z512. The porphyrin arrays up to Z128 are sufficiently soluble in CHCl3 and THF despite their very long molecular lengths and rodlike structures, while the arrays over Z128 show a significant drop in solubility and stability. The discrete porphyrin arrays thus isolated were characterized by means of (1)H NMR spectroscopy, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, UV/Vis spectroscopy, gel-permeation chromatography (GPC), cyclic voltammetry (CV), single-crystal X-ray crystallography, scanning tunneling microscopy (STM), and atomic force microscopy (AFM). Contrary to expected linear conformations of the arrays Z n (where n is the number of porphyrins), the single molecular images of Z128, Z256, and Z512 revealed largely bent structures; this finding indicates the substantial conformational flexibility of Z n. We also exploited an effective synthetic route by means of which Z n can be fabricated with a thiol-protected aryl group to provide Z n S(2) through Z n Br(2), by bromination with N-bromosuccinimide and subsequent Pd-catalyzed Suzuki-Miyaura arylation. Finally, the reaction of Z256 provided Z512, Z768, and Z1024. Collectively, this work provides an important milestone in the preparation of sub-microscale discrete organic molecules and the fabrication of molecular-based materials, hence significantly contributing to device applications.     

Total synthesis and complete assignment of the stereostructure of a cytotoxic bromotriterpene polyether (+)-aurilol

The plane structure and partial stereochemistry of a cytotoxic bromotriterpene polyether (+)-aurilol (1), isolated from the sea hare Dolabella auricularia, were mainly elucidated by NMR methods; however, determination of the entire stereochemistry has not been reached. Although there have also been many other types of triterpene polyethers, it is often difficult to determine their stereostructures even by the current highly advanced spectroscopic methods, especially in acyclic systems including quaternary carbon centers such as C10-C11, C14-C15, and C18-C19 in 1. In this paper, we report that the total assignment of the incomplete stereostructure of (+)-aurilol (1) to the structural formula 2 has been accomplished through its first asymmetric total synthesis featuring the highly regio- and stereocontrolled biogenetic-like A-D ether ring formations.     

Fc-binding antibody-recruiting molecules exploit endogenous antibodies for anti-tumor immune responses

Redirecting endogenous antibodies in the bloodstream to tumor cells using synthetic molecules is a promising approach to trigger anti-tumor immune responses. However, current molecular designs only enable the use of a small fraction of endogenous antibodies, limiting the therapeutic potential. Here, we report Fc-binding antibody-recruiting molecules (Fc-ARMs) as the first example addressing this issue. Fc-ARMs are composed of an Fc-binding peptide and a targeting ligand, enabling the exploitation of endogenous antibodies through constant affinity to the Fc region of antibodies, whose sequence is conserved in contrast to the Fab region. We show that Fc-ARM targeting folate receptor-α (FR-α) redirects a clinically used antibody mixture to FR-α⁺ cancer cells, resulting in cancer cell lysis by natural killer cells in vitro. Fc-ARMs successfully interacted with antibodies in vivo and accumulated in tumors. Furthermore, Fc-ARMs recruited antibodies to suppress tumor growth in a mouse model. Thus, Fc-ARMs have the potential to be a novel class of cancer immunotherapeutic agents.

Fc-binding antibody-recruiting molecules provide robust and sufficient opportunities to employ endogenous antibodies for anti-tumor immune responses.     

Isotactic poly(acrylonitrile) via ultraviolet irradiation of acrylonitrile-urea canal complex

Isotactic poly(acrylonitrile) (PAN) has been prepared by means of a conventional ultraviolet (UV) irradiation apparatus without γ-ray sources; an acrylonitrile-urea canal complex was directly formed at the surface of the UV (Hg) emission tube at low temperatures (～ ?78°C). When the complex was UV-irradiated at this temperature, a stereoregular polymer was formed in the canal. The ¹³C-NMR analyses indicate that (1) these PAN are rich in isotactic configuration, (2) the extent of the isotactic triad is in the range of 56?71%, and (3) the penultimate unit effect, 4 (mm) (rr)/(mr)², is linearly correlated with the ultimate unit effect, (mm)/(rr). From the plots of log{4(mm)(rr)/(mr)²} vs log{(mm)/(rr)}, the anomaly in the polymerization of AN is discussed. The molecular characteristics of the UV canal PAN such as molecular weight, etc., were briefly noted. © 1995 John Wiley & Sons, Inc.     

Palladium-catalyzed transformation of cyclobutanone O-benzoyloximes to nitriles via C-C bond cleavage

Palladium-catalyzed transformation of cyclobutanone O-benzoyloximes to a variety of nitriles is described. The reaction may proceed via two important steps, that is, (i) oxidative addition of the N-O bond of oximes to Pd(0) to give a cyclobutylideneaminopalladium(II) species and (ii) beta-carbon elimination of this species to afford a reactive alkylpalladium species. The kind of products is very dependent on the nature of substituents on the cyclobutane ring. The direction of the C-C bond cleavage is controlled by the kind of ligand employed. The sequential reaction composed of the C-C bond cleavage and the subsequent intra- and intermolecular C-C bond formations via the corresponding alkylpalladium species is also demonstrated. For example, an oxime having an alkynyl moiety at a suitable position reacts with a variety of alkenes to afford nitriles bearing dienylcyclopentane moiety in moderate to good yields.     

Interconversion between bis(mu-thiolato)dicopper(II) and disulfide-bridged dicopper(I) complexes mediated by chloride ion

An unprecedented clean interconversion between a novel bis(mu-thiolato)dicopper(II) complex (1) and a disulfide-bridged dicopper(I) complex (3) through a disulfide-bridged (mu-chloro)dicopper(I) complex (2) mediated by chloride ion has been established for the first time, providing a new redox chemistry of the transition metal-sulfur complexes. Crystal structures of 1 and 3 as well as spectroscopic features of the compounds are reported.