Isoschizogamine is a member of the schizozygane family of indole
alkaloids. Its highly fused hexacyclic structure containing an aminal adjacent
to a quaternary stereocenter makes it a challenging synthetic target. While the authors reported the total synthesis of
(–)-isoschizogamine in 2012, this paper describes an alternative preparation of
their pivotal synthetic intermediate. The synthesis features a stereoselective
construction of a quaternary carbon by the Claisen-Johnson rearrangement and a
stereoselective rhodium-mediated 1,4-addition of arylboronic acid. The
reliability of this synthetic route enables a
sufficient supply of the intermediate for the total synthesis of isoschizogamine.
of repeatability in supercritical fluid chromatography with electrochemical
detection (SFC-ECD) system is necessary to construct an SFC-ECD as a
quantitative method with satisfactory precision. This article is the first report that a
method for the assessment of repeatability in SFC-ECD has been proposed by
means of the ISO 11843 part 7 which can theoretically provide detection limits
and standard deviation (SD) through the stochastic properties of baseline noise
without repetitive measurements of real samples. The present method is practically useful,
and both experimental time and chemicals can be saved to estimate the
repeatability in SFC-ECD.
A series of 8-methoxy or
8-methylquinolones bearing novel 3-aminooctahydrocyclopenta[c]pyrrole
derivatives at the C-7 position was synthesized, and the pharmacological,
physicochemical, and toxicological properties of the individual compounds were
evaluated. Novel 7-[(1R,5S)-1-amino-5-fluoro-3-azabicyclo[3.3.0]octan-3-yl]-6-fluoro-8-methylquinolone
7 exhibited potent and better activity than
LVFX and MFLX against streptococci, staphylococci, enterococci, E. coli, A. baumannii, and anaerobes. Compound 7 also demonstrated favorable
pharmacokinetic and pharmacodynamic properties and an acceptably safe
toxicological profile. Consequently, compound 7 was selected as a clinical candidate for further evaluation as a new-generation,
broad-spectrum quinolone antibiotic. Compound 7 is expected to become an option for antibacterial therapy against multidrug-resistant A.
Polygenetic and complex diseases are great burden
and challenge of human, such as ischemic cerebrovascular disease (ICD) and
cardiovascular diseases (CVD). Drug repositioning, is one important approach to
reexamine the new indications of marketed drugs, especially drugs with
multi-targets. Based on the interplay among diseases, genes (targets) and
drugs, new method can be applied to dissect the association information. A
multi-database, in silico target identification, gene function enrichment, and
network pharmacology analysis integrated methods were proposed to investigate
the approved CVD drugs repurposing for ICD. It provides promising alternative
to inferring novel disease indications for existing safe and effective drugs.
Oxiranyl anions are very unstable and uncommon
nucleophiles while epoxies are widely used as electrophiles in organic chemistry.
A sulfonyl-stabilized oxiranyl anion reacts efficiently with a triflate to afford
an alkylated product in high yield. The high synthetic potential of the
oxiranyl anion chemistry was demonstrated by the total synthesis of gymnocin-A,
a cytotoxic polycyclic ether marine natural product produced by the red tide
organism Karenia mikimotoi.
New Cannabinoid-Like Chromane and Chromene Derivatives from Rhododendron anthopogonoides
Released: November 01, 2011 | Volume 59 Issue 11 Pages 1409-1412
Naoki Iwata, Susumu Kitanaka