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Axially chiral diaryl ethers are a type of unique atropisomers bearing two potential axes, which have potential applications in a variety of research fields. However, the catalytic enantioselective synthesis of these diaryl ether atropisomers is largely underexplored when compared to the catalytic asymmetric synthesis of biaryl or other types of atropisomers. Herein, we report a highly efficient catalytic asymmetric synthesis of diaryl ether atropisomers through an organocatalyzed enantioselective desymmetrization protocol. The chiral phosphoric acid-catalyzed asymmetric electrophilic aromatic aminations of the symmetrical 1,3-benzenediamine type substrates afforded a series of diaryl ether atropisomers in excellent yields and enantioselectivities. The facile construction of heterocycles by the utilizations of the 1,2-benzenediamine moiety in the products provided access to a variety of structurally diverse and novel azaarene-containing diaryl ether atropisomers., (© 2023 Wiley-VCH GmbH.)

An efficient approach for asymmetric synthesis of planar-chiral macrocycles (paracyclophanes) has been disclosed through enantioselective electrophilic aromatic aminations with azodicarboxylates enabled by chiral phosphoric acid catalysis. A wide range of chiral macrocycles bearing varied ring sizes (16 to 23-membered) and functional group-containing ansa chains were readily afforded using this method, with excellent yields and high enantioselectivities (23 examples, up to 99.5 : 0.5 er). Experimental studies and DFT calculations were performed to elucidate the mechanism and origin of stereoselectivities of these reactions. Preliminary utilization of the planar-chiral macrocycle as chiral organocatalyst showcased the potential applications of these novel chiral skeletons., (© 2022 Wiley-VCH GmbH.)

A Ni-catalyzed reductive cross-coupling between α-C-tosyl peptides and Csp 2 triflates/halides has been developed. This protocol enables the formation of various unnatural di- and tripeptides containing vinyl and aryl side chains, and it expands the applications of Ni-catalyzed reductive cross-coupling in late-stage diversification of peptides.

Objective: To explore the regulatory mechanism of Siahl in the pathogenesis of hypoxic pulmonary hypertension (HPH) in rats., Methods: According to the random number table, 40 adult male Wistar rats were randomly divided into 5 groups (n = 8 each). And the animals were exposed to normoxia or hypoxia for 3, 7, 14 or 21 days respectively. The HPH model was established by normobaric intermittent hypoxia. Mean pulmonary arterial pressure (mPAP), ratio of vascular wall area to total vascular area (WA%), ratio of vascular lumen area to total vascular area (LA%) and right ventricle hypertrophy index (RVHI) were measured. The mRNA and protein relative levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were detected by in situ hybridization and immunohistochemistry respectively. Reverse transcriptase-polymerase chain reaction ( RT-PCR) and in situ hybridization were used to determine the relative expressions of mRNA of hypoxia-inducible factor-1 (FIH) and Siahl. Immunohistochemistry and Western blot were employed to determine the relative expressions of proteins of FIH and Siahl., Results: The levels of mPAP, WA% and LA% were significantly higher after 7-day hypoxia than those in normoxic control (21. 3 1. 6) vs (15. 9 ± 1. 3) mmHg (1 mmHg = 0. 133 kPa), (41.4 ± 2.8)% vs (35.0 ± 2.2)%, (58.6 ± 2.8)% vs (65.0 ± 2.2)%, all P <0.05). The level of RVHI was significantly higher after 14-day hypoxia than that in normoxic control ((27. 0 ± 1. 8) % vs (3. 2 ± 2. 1) %, P <0. 05). The relative expression of HIF-1α mRNA was significantly higher after 14-day hypoxia than that in normoxic control (0. 188 ± 0. 014 vs 0. 150 ± 0. 014, P < 0. 05). The relative expression of HIF-1α protein was significantly higher after 3-day hypoxia than that in normoxic control (0. 186 ± 0.014 vs 0. 067 ± 0.008, P <0.05). The relative levels of VEGF mRNA and protein were significantly higher after 7-day hypoxia than those in normoxic control (0. 152 ± 0. 019 vs 0. 057 ± 0. 007, 0. 176 ± 0. 017 vs 0. 083 ± 0. 010, both P <0. 05). The relative expression of FIH mRNA had little changes after exposure to hypoxia compared with normoxia. However the related expression of FIH protein was markedly lower after 7-day hypoxia than that in normoxic control (0. 166 ± 0. 015 vs 0. 200 ± 0. 017, P < 0. 05). The relative levels of Siahl mRNA and protein were markedly higher after 7-day hypoxia than those in normoxic control (0. 144 ± 0. 014 vs 0. 067 ± 0. 010, 0. 136 ± 0. 017 vs 0. 084 ± 0. 019, both P <0. 05). Linear correlation analysis showed that HIF-1α protein was positively correlated with the relative levels of VEGF mRNA and VEGF protein (r = 0. 545, 0. 523, both P <0. 01) while FIH protein was negatively correlated with the relative levels of VEGF mRNA and VEGF protein (r = -0. 785, -0. 788, both P < 0. 01). There was a positive correlation between the relative levels of Siahi mRNA and Siahl protein (r = 0. 823, P <0. 01) while a negative correlation existed between the relative levels of Siahl protein and FIH protein (r = -0. 671, P <0. 01)., Conclusions: Under chronic hypoxia, Siahl is transcriptionally induced in pulmonary arterioles and it facilitates the degradation and decline of FIR in rats. And deceased FIH protein in pulmonary arterioles under hypoxia may attenuate its inhibitory effect on the transactivational activity of HIF-l a and promote the transactivation of such HIF-1α target gene as VEGF. Thus it is probably implicated in the pathogenesis of HPH.