Organocatalytic Atroposelective Construction of Axially Chiral Nonsymmetric Biaryltriols and Their Applications on Asymmetric Synthesis and Heavy Metal Ion Detection

An organocatalytic methodology toward the atroposelective construction of axially chiral nonsymmetric biaryltriols has been successfully developed. Quinine-derived thiourea-catalyzed intramolecular reaction through VQM (vinylidene ortho-quinone methides) intermediate enabled efficient access to...

Modelling STEMI service delivery: a proof of concept study

BackgroundAccess to individual percutaneous coronary intervention (PCI) centres has traditionally been determined by historical referral patterns along arbitrarily defined geographic boundaries. We set out to produce predictive models of ST-elevation myocardial infarction (STEMI) demand and time-efficient access to PCI centres.MethodsTravel times from random addresses to PCI centres in Melbourne, Australia, were estimated using Google map application programming interface (API). Departures at 08:15 and 17:15 were compared with 23:00 to determine the effect of peak hour traffic congestion. Real-world ambulance travel times were compared with estimated travel times using Google map developer software. STEMI incidence per postcode was estimated by merging STEMI incidence per age group data with age group per postcode census data. PCI centre network configuration changes were assessed for their effect on hospital STEMI loading, catchment size, travel times and the number of STEMI cases within 30 min of a PCI centre.ResultsNearly 10% of STEMI cases travelled more than 30 min to a PCI centre, increasing to 20% by modelling the removal of large outer metropolitan PCI centres (p<0.05). A model of 7 PCI centres compared favourably to the current existing network of 11 PCI centres (p=0.18 (afternoon), p=0.5 (morning and night)). The intraclass correlation between estimated travel times and ambulance travel times was 0.82, p<0.001.ConclusionThis paper provides a framework to integrate prehospital environmental variables, existing or altered healthcare resources and health statistics to objectively model STEMI demand and consequent access to PCI. Our methodology can be modified to incorporate other inputs to compute optimum healthcare efficiencies.

Organocatalytic Discrimination of Non-Directing Aryl and Heteroaryl Groups: Enantioselective Synthesis of Bioactive Indole-Containing Triarylmethanes

Despite the enormous developments of asymmetric catalysis, the basis for asymmetric induction is largely limited to spatial interaction between substrate and catalyst. Consequently, asymmetric discrimination between two sterically similar groups remains a challenge. This is particularly formidable for enantiodifferentiation between aryl and heteroaryl groups without a directing group or electronic manipulation. Here we address this challenge by a robust organocatalytic system leading to excellent enantioselection between aryl and heteroaryl groups. With the versatile 2-indole imine methide as platform, an excellent combination of a superb chiral phosphoric acid and the optimal hydride source provided efficient access to a range of highly enantioenriched indole-containing triarylmethanes. Control experiments and kinetic studies provided important insights into the mechanism. DFT calculations also indicated that, while hydrogen bonding is important for activation, the key interaction for discrimination of the two aryl groups is mainly π-π stacking. Preliminary biological studies also demonstrated the great potential of these triarylmethanes for anticancer and antiviral drug development.

Organocatalytic Discrimination of Non-Directing Aryl and Heteroaryl Groups: Enantioselective Synthesis of Bioactive Indole-Containing Triarylmethanes

Despite the enormous developments of asymmetric catalysis, the basis for asymmetric induction is largely limited to spatial interaction between substrate and catalyst. Consequently, asymmetric discrimination between two sterically similar groups remains a challenge. This is particularly formidable for enantiodifferentiation between aryl and heteroaryl groups without a directing group or electronic manipulation. Here we address this challenge by a robust organocatalytic system leading to excellent enantioselection between aryl and heteroaryl groups. With the versatile 2-indole imine methide as platform, an excellent combination of a superb chiral phosphoric acid and the optimal hydride source provided efficient access to a range of highly enantioenriched indole-containing triarylmethanes. Control experiments and kinetic studies provided important insights into the mechanism. DFT calculations also indicated that, while hydrogen bonding is important for activation, the key interaction for discrimination of the two aryl groups is mainly π-π stacking. Preliminary biological studies also demonstrated the great potential of these triarylmethanes for anticancer and antiviral drug development.