3 research outputs found
Chemoselective Boron-Catalyzed Nucleophilic Activation of Carboxylic Acids for Mannich-Type Reactions
The carboxyl group
(COOH) is an omnipresent functional group in
organic molecules, and its direct catalytic activation represents
an attractive synthetic method. Herein, we describe the first example
of a direct catalytic nucleophilic activation of carboxylic acids
with BH<sub>3</sub>·SMe<sub>2</sub>, after which the acids are
able to act as carbon nucleophiles, i.e. enolates, in Mannich-type
reactions. This reaction proceeds with a mild organic base (DBU) and
exhibits high levels of functional group tolerance. The boron catalyst
is highly chemoselective toward the COOH group, even in the presence
of other carbonyl moieties, such as amides, esters, or ketones. Furthermore,
this catalytic method can be extended to highly enantioselective Mannich-type
reactions by using a (<i>R</i>)-3,3′-I<sub>2</sub>-BINOL-substituted boron catalyst
Chemo- and Enantioselective Pd/B Hybrid Catalysis for the Construction of Acyclic Quaternary Carbons: Migratory Allylation of <i>O</i>‑Allyl Esters to α‑<i>C</i>‑Allyl Carboxylic Acids
We
describe herein the asymmetric synthesis of α-allyl carboxylic
acids containing an α-quaternary stereocenter by a chiral hybrid
catalyst system comprising palladium and boron complexes. The reaction
proceeded through palladium-catalyzed ionization of α,α-disubstituted <i>O</i>-allyl esters for the generation of chiral π-allyl
palladium complex as an electrophile, boron-catalyzed enolization
of the carboxylate part for the generation of chiral α,α-disubstituted
carboxylic acid-derived enolates as a nucleophile, and enantioselective
coupling between the thus-generated nucleophile and electrophile.
Proper combinations of chiral ligands for the boron and palladium
catalysts were crucial. The reaction proceeded chemoselectively at
the α-position of the carboxylic acid group
Prediction of Response to Treatment by Gene Expression Profiling of Peripheral Blood in Patients with Microscopic Polyangiitis
<div><p>The JMAAV study was an open-labeled prospective clinical trial, which proposed severity-based treatment protocols for patients with microscopic polyangiitis (MPA). The results suggest that the proposed protocols are useful (remission rate: 89.4%), but are also indicative of relapse or patient demise regardless of the treatment (recurrence rate: 19.0%; mortality rate: 10.6%). The aim of this study is to develop the method to predict response to the treatment in patients with MPA. In the present study, transcriptome analysis was performed using peripheral blood from patients enrolled in the JMAAV study before and 1-week after the beginning of treatment. The gene expression profile before treatment was not directly related to the response to the treatment. However, when the samples from 9 patients with good response (persistent remission for 18 months) were examined, the expression of 88 genes was significantly altered by the treatment. Thirty statistically reliable genes were selected, and then the alteration of expression by the treatment was examined among 22 patients, including 17 with good response, which was defined as persistent remission for 18 months and 5 with poor response, which was defined as relapse after remission or no remission. Discrimination analysis between the alteration of expression of the 30 genes by the treatment and the response identified a combination of 16 genes as the most valuable gene set to predict the response to the treatment. This preliminary study identified IRF7, IFIT1, IFIT5, OASL, CLC, GBP-1, PSMB9, HERC5, CCR1, CD36, MS4A4A, BIRC4BP, PLSCR1, DEFA1/DEFA3, DEFA4, and COL9A2 as the important genes that can predict the response to the treatment in patients with MPA at an early point during the therapy.</p></div