A palladium-catalyzed, enantioselective allylic C–H alkylation of 1,4-pentadienes with 5H-thiazol-4-ones has been developed. Under the cooperative catalysis of a palladium complex of chiral ...phosphoramidite ligand and an achiral Brønsted acid, a broad range of substituted 5H-thiazol-4-ones bearing sulfur-containing tertiary chiral centers were accessed from the allylic C–H alkylation in high levels of yields and enantioselectivities. Alkyl and aryl 1,4-pentadienes led to linear and branched allylation products, respectively.
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IJS, KILJ, NUK, PNG, UL, UM
Visible light-driven pyridoxal radical biocatalysis has emerged as a promising strategy for the stereoselective synthesis of valuable noncanonical amino acids (ncAAs). Previously, the use of ...well-tailored photoredox catalysts represented the key to enable efficient pyridoxal phosphate (PLP) enzyme-catalyzed radical reactions. Here, we report a PLP-dependent threonine aldolase-catalyzed asymmetric α-C-H alkylation of abundant amino acids using Katritzky pyridinium salts as alkylating agents. The use of engineered threonine aldolases allowed for this redox-neutral radical alkylation to proceed efficiently, giving rise to challenging α-trisubstituted and -tetrasubstituted ncAA products in a protecting-group-free fashion with excellent enantiocontrol. Mechanistically, this enantioselective α-alkylation capitalizes on the unique reactivity of the persistent enzymatic quinonoid intermediate derived from the PLP cofactor and the amino acid substrate to allow for novel radical C-C coupling. Surprisingly, this photobiocatalytic process does not require the use of well-established photoredox catalysts and operates through an unconventional photoinduced radical generation involving a PLP-derived aldimine. The ability to develop photobiocatalytic reactions without relying on classic photocatalysts or photoenzymes opens up new avenues for advancing stereoselective intermolecular radical reactions that are not known in either organic chemistry or enzymology.Visible light-driven pyridoxal radical biocatalysis has emerged as a promising strategy for the stereoselective synthesis of valuable noncanonical amino acids (ncAAs). Previously, the use of well-tailored photoredox catalysts represented the key to enable efficient pyridoxal phosphate (PLP) enzyme-catalyzed radical reactions. Here, we report a PLP-dependent threonine aldolase-catalyzed asymmetric α-C-H alkylation of abundant amino acids using Katritzky pyridinium salts as alkylating agents. The use of engineered threonine aldolases allowed for this redox-neutral radical alkylation to proceed efficiently, giving rise to challenging α-trisubstituted and -tetrasubstituted ncAA products in a protecting-group-free fashion with excellent enantiocontrol. Mechanistically, this enantioselective α-alkylation capitalizes on the unique reactivity of the persistent enzymatic quinonoid intermediate derived from the PLP cofactor and the amino acid substrate to allow for novel radical C-C coupling. Surprisingly, this photobiocatalytic process does not require the use of well-established photoredox catalysts and operates through an unconventional photoinduced radical generation involving a PLP-derived aldimine. The ability to develop photobiocatalytic reactions without relying on classic photocatalysts or photoenzymes opens up new avenues for advancing stereoselective intermolecular radical reactions that are not known in either organic chemistry or enzymology.
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IJS, KILJ, NUK, PNG, UL, UM
Background： Acute abdominal pain is a common symptom of emergency patients. The severity was always evaluated based on physicians＇ clinical experience. The aim of this study was to establish an early ...risk stratification method （ERSM） for addressing adults with acute abdominal pain, which would gnide physicians to take appropriate and timely measures following the established health-care policies. Methods： In Cohort 1, the records of 490 patients with acute abdominal pain that developed within the past 72 h were enrolled in this study. Measurement data and numeration data were compared with analysis of variance and Chi-square test, respectively. Multiple regression analysis calculated odd ratio （OR） value. P and OR values showed the impacts of factors. ERSM was established by clinical experts and statistical experts according to Youden index. In Cohort 2, data from 305 patients with acute abdominal pain were enrolled to validate the accuracy of the ERSM. Then, ERSM was prospectively used in clinical practice. Results： The ERSM was established based on the scores of the patient＇s clinical characteristics： right lower abdominal pain ＋ 3 × diffuse abdominal pain ＋ 3 ×cutting abdominal pain ＋ 3 × pain frequency ＋ 3 × pain duration ＋ fever ＋ 2 × vomiting ＋ 5 × stop defecation ＋ 3 - history of abdominal surgery ＋ hypertension history ＋ diabetes history ＋ hyperlipidemia history ＋ pulse ＋ 2 - skin yellowing ＋ 2 × sclera yellowing ＋ 2 × double lung rale ＋ 10 × unconsciousness ＋ 2 ×right lower abdominal tenderness ＋ 5 x diffuse abdominal tenderness ＋ 4 x peritoneal irritation ＋ 4 × bowel sounds abnormal ＋ 10 × suspicious diagnosis ＋ white blood cell count ＋ hematocrit ＋ glucose ＋ 2 × blood urea nitrogen ＋ 3 × creatine ＋ 4× serum albumin ＋ alanine aminotransferase ＋ total bilirubin ＋ 3 × conjugated bilirubin ＋ amylase. When the score was 〈18, the patient did not need hospitalization. A score of≥18 and 〈38 indicated that the patient should be under observation or hospitalized. A score of≥38 and 〈50 indicated the need for an emergent operation. A score of≥50 indicated the need for admission to the Intensive Care Unit. The area under the receiver operating characteristic curve of the ERSM in Cohorts 1 and 2 were 0.979 and 0.988, respectively. Conclusions： This ERSM was an accurate and reliable method for making an early determination of the severity of acute abdominal pain. There was the strong correlation between scores of ERSM and health-care decision-making.
Abstract
C
19
H
12
ClF
2
N
5
O
2
, monoclinic,
P
2
1
/
n
(no. 14),
a
= 14.405(9) Å,
b
= 7.579(5) Å,
c
= 17.610(9) Å,
β
= 95.856(13)°,
V
= 1913(2) Å
3
,
Z
= 4,
R
gt
(
F
) = 0.0464,
wR
ref
(
F
2
...) = 0.1134, T = 296 K.
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