Copper-Catalyzed Aza-Michael Addition of Aromatic Amines or Aromatic Aza-Heterocycles to α,β-Unsaturated Olefins

A highly efficient and mild Cu-catalyzed conjugate addition reaction of aromatic amines and aromatic aza-heterocycles to α,β-unsaturated olefins is described. The transformation is promoted by 3–7 mol % of a Cu complex generated in situ from a mixture of inexpensive CuCl, a readily available phosphine or imidazolium salt, and KO<i>t</i>-Bu at ambient temperature. A wide range of β-amino sulfone, β-amino nitrile, and β-amino carbonyl compounds is efficiently and selectively synthesized in high yields (62–99%)

Comparison of relative abundances of predicted KEGG functional pathway analysis between Aβ+ CN participants and Aβ− CN participants.

(PDF)</p

Receiver operating characteristic (ROC) curve analysis of the multivariate logistic model to detect preclinical AD using microbiome.

The blue line represents the model with the presence or absence of nine genera revealed from the GLM analysis and covariates (i.e., age, sex, APOE4 positivity and BMI), while a green line represents the reference model including only the covariates. Abbreviation. AD: Alzheimer’s disease; APOE4: apolipoprotein E ε4; BMI: body mass index.</p

S2 Fig -

β-diversities of the fecal microbiome between Aβ− CN participants and Aβ+ CN participants based on (A) Bray-Curtis (B) unweighted UniFrac (C) weighted UniFrac and (D) Aitchison values. Abbreviations. Aβ+ CN: cognitively normal participants with amyloid retention; Aβ− CN: cognitively normal participants without amyloid retention. (TIF)</p

GLM analysis results of taxonomic differences in microbiome between Aβ+ CN participants and Aβ− CN participants.

GLM analysis results of taxonomic differences in microbiome between Aβ+ CN participants and Aβ− CN participants.</p

Participant characteristics.

Participant characteristics.</p

Log predicted counts of the genera associated with Aβ positivity.

Prediction was made using GLM analysis adjusted for age, gender, BMI, APOE4 positivity. Only genera with q <0.05 are shown. Abbreviation. Aβ: amyloid beta; GLM: generalized linear model; Aβ+ CN: cognitively normal participants with amyloid retention Aβ− CN: cognitively normal participants without amyloid retention; APOE4: apolipoprotein E ε4; BMI: body mass index.</p

Relative differences in predicted gene contents in microbiome between Aβ− CN participants and Aβ+ CN participants.

Abbreviations. Aβ+ CN: cognitively normal participants with amyloid retention Aβ− CN: cognitively normal participants without amyloid retention.</p

S1 Fig -

Comparison of α-diversities of the fecal microbiome between Aβ− CN participants and Aβ+ CN participants according to (A) evenness (B) observed species (C) Shannon index and (D) phylogenic diversity (PD). Abbreviations. Aβ+ CN: Cognitively normal participants with amyloid retention; Aβ− CN: Cognitively normal participants without amyloid retention; PD: phylogenetic diversity. (TIF)</p