Synthesis of Sulfonylated Lactams by Copper-Mediated Aminosulfonylation of 2-Vinylbenzamides with Sodium Sulfinates.

Treatment of 2-vinylbenzamide derivatives with sulfinate sodium in the presence of Cu(NO3)2·3H2O led to an intra/intermolecular aminosulfonylation reaction to produce sulfonylated lactams in moderate to good yields. The developed method features the easily available and stable sulfone reagents, ease of operation, and a broad functional group tolerance.

Radiosynthesis of a carbon-11-labeled AMPAR allosteric modulator as a new PET radioligand candidate for imaging of Alzheimer's disease.

To develop PET tracers for imaging of Alzheimer's disease, a new carbon-11-labeled AMPAR allosteric modulator 4-cyclopropyl-7-(3-[11C]methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide ([11C]8) has been synthesized. The reference standard 4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide (8) and its corresponding desmethylated precursor 4-cyclopropyl-7-(3-hydroxyphenoxy)-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide (9) were synthesized from 4-methoxyabiline and chlorosulfonyl isocyanate in eight and nine steps with 3% and 1% overall chemical yield, respectively. The target tracer [11C]8 was prepared from the precursor 9 with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 10-15% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (AM) at EOB was 370-740 GBq/µmol with a total synthesis time of 35-40-minutes from EOB.

Facile synthesis of carbon-11-labeled sEH/PDE4 dual inhibitors as new potential PET agents for imaging of sEH/PDE4 enzymes in neuroinflammation.

To develop PET tracers for imaging of neuroinflammation, new carbon-11-labeled sEH/PDE4 dual inhibitors have been synthesized. The reference standard N-(4-methoxy-2-(trifluoromethyl)benzyl)benzamide (1) and its corresponding desmethylated precursor N-(4-hydroxy-2-(trifluoromethyl)benzyl)benzamide (2) were synthesized from (4-methoxy-2-(trifluoromethyl)phenyl)methanamine and benzoic acid in one and two steps with 84% and 49% overall chemical yield, respectively. The standard N-(4-methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (MPPA, 4) and its precursor N-(4-hydroxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (5) were synthesized from methyl 4-piperidinecarboxylate, propionyl chloride and (4-methoxy-2-(trifluoromethyl)phenyl)methanamine in two and three steps with 62% and 34% overall chemical yield, respectively. The target tracers N-(4-[11C]methoxy-2-(trifluoromethyl)benzyl)benzamide ([11C]1) and N-(4-[11C]methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide ([11C]MPPA, [11C]4) were prepared from their corresponding precursors 2 and 5 with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 25-35% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (AM) at EOB was 370-740 GBq/µmol with a total synthesis time of 35-40-minutes from EOB.

Synthesis of carbon-11-labeled 5-HT6R antagonists as new candidate PET radioligands for imaging of Alzheimer's disease.

Carbon-11-labeled serotonin (5-hydroxytryptamine) 6 receptor (5-HT6R) antagonists, 1-[(2-bromophenyl)sulfonyl]-5-[11C]methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole (O-[11C]2a) and 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-[11C]methyl-1-piperazinyl)methyl]-1H-indole (N-[11C]2a), 5-[11C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (O-[11C]2b) and 5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (N-[11C]2b), 1-((4-isopropylphenyl)sulfonyl)-5-[11C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1H-indole (O-[11C]2c) and 1-((4-isopropylphenyl)sulfonyl)-5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1H-indole (N-[11C]2c), 1-((4-fluorophenyl)sulfonyl)-5-[11C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1H-indole (O-[11C]2d) and 1-((4-fluorophenyl)sulfonyl)-5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1H-indole (N-[11C]2d), were prepared from their O- or N-desmethylated precursors with [11C]CH3OTf through O- or N-[11C]methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370-740 GBq/µmol with a total synthesis time of ∼40-min from EOB.

A study on the two-level allocation of carbon emission quotas in China at the provincial level.

Carbon emission reduction is an essential means to achieve the "double carbon goal," and the scientific and reasonable allocation of carbon emission quotas (CEQ) is the basis for promoting carbon emission reduction. In this study, the first level was based on the entropy TOPSIS scores of provinces under the principles of fairness, efficiency, sustainability, and feasibility and used the K-mean clustering method to cluster the 30 provinces and allocate the CEQ to each zone group; the second level consolidated the impacts of the four principles and the marginal abatement costs of CO2 to allocate CEQ to the provinces within the zone group. Finally, each province's initial spatial balance of CEQ (ISBQ) is classified and evaluated. The study shows that the most quotas are for Guangdong, Zhejiang, and Inner Mongolia, and the least for Ningxia, Shanxi, and Guizhou. This study compares the results of CEQ allocation with the current carbon emission scale and finds that 11 provinces, such as Shandong and Hebei, show a deficit in future carbon emission space, and 19 provinces, such as Hainan and Beijing, show a surplus in carbon emission space. Given each province's different emission reduction tasks and pressures, differentiated emission control policies are the key to achieving China's "2030 target".

Simulation study on the development decision of new energy manufacturers under the weight of consumption responsibility.

In 2019, China proposed the weight of consumption responsibility (WCR) policy for renewable energy. This study first analyzes the interaction between the electricity market and the green certificate market and establishes a two-market equilibrium model with multiple subjects. Secondly, a system dynamics model of the development decision of the new energy manufacturers (NEMs) under the interaction of the two markets is established. Finally, taking Henan province as an example, the development trend of NEMs is simulated, and sensitivity analysis is conducted to explore the key influencing factors for the development of NEMs. The results show that the electricity market and the green certificate market interact with each other mainly through the price of electricity and the price of green certificates, thus evolving the trading behavior of trading subjects. By 2035, for every 0.25% increase in non-hydropower WCR in Henan province, the annual added new energy installation will be around 1200 MW. In the current scenario, the policy of certificate multiplier will be detrimental to the overall development of NEMs, and a conservative investment strategy and accelerated technology improvements are more beneficial to NEMs. Carbon emission peaking and carbon neutrality policies can also accelerate the growth of new energy installations.

Optimal dispatch of integrated energy system with P2G considering carbon trading and demand response.

How to maintain the economic and low-carbon operation of the integrated energy system (IES) while taking into account the interests of the user side is of great significance to promote the large-scale development of IES. For this reason, this paper takes IES with the electricity-to-gas device as the research object and first constructs a demand response model that takes into account the user's energy experience and a reward and punishment ladder carbon trading model. Second, an IES game optimization framework considering carbon trading and demand response is proposed. On this basis, taking the operators and users of the integrated energy system as the main players of the game, a two-level game optimization scheduling model is constructed to synchronously improve the economic, low-carbon, and satisfactory operation of IES, and the proposed model is solved by the combination of particle swarm optimization and CPLEX. Finally, the simulation shows that the proposed model can effectively enhance the benefits of both supply and demand while reflecting the user response behavior more realistically.

Radiosynthesis of a carbon-11 labeled tetrahydrobenzisoxazole derivative as a new PET probe for γ-secretase imaging in Alzheimer's disease.

To develop PET radiotracers for imaging of Alzheimer's disease, a new carbon-11 labeled potent and selective γ-secretase modulator (GSM) has been synthesized. The reference standard tetrahydrobenzisoxazole derivative 8 and its desmethylated precursor 9 were synthesized from cyclohex-2-en-1-one and 3-hydroxy-4-nitrobenzaldehyde in eight and nine steps with 11% and 5% overall chemical yield, respectively. The radiotracer [11C]8 was prepared from its corresponding precursor 9 with [11C]CH3OTf through O-11C-methylation and isolated by RP-HPLC combined with SPE in 45-50% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (Am) at EOB was 555-740 GBq/µmol.

Radiosynthesis of carbon-11 labeled PDE5 inhibitors as new potential PET radiotracers for imaging of Alzheimer's disease.

To develop PET tracers for imaging of Alzheimer's disease, new carbon-11 labeled potent and selective PDE5 inhibitors have been synthesized. The reference standards (5) and (12), and their corresponding desmethylated precursors (6) and (13) were synthesized from methyl 2-amino-5-bromobenzoate and (4-methoxyphenyl)methanamine in multiple steps with 2%, 1%, 1% and 0.2% overall chemical yield, respectively. The radiotracers ([11C]5) and ([11C]12) were prepared from their corresponding precursors 6 and 13 with [11C]CH3OTf through O-11C-methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the molar activity (Am) at EOB was in a range of 370-740 GBq/µmol.

Synthesis of N-(3-(4-[11C]methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a new potential PET agent for imaging of IRAK4 enzyme in neuroinflammation.

The reference standard N-(3-(4-methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (9) and its demethylated precursor N-(1-(5-methylpyridin-2-yl)-3-(piperazin-1-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (8) were synthesized from pyrazolo[1,5-a]pyrimidine-3-carboxylic acid and ethyl 2-cyanoacetate with overall chemical yield 13% in nine steps and 14% in eight steps, respectively. The target tracer N-(3-(4-[11C]methylpiperazin-1-yl)-1-(5-methylpyridin-2-yl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([11C]9) was prepared from its precursor with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 50-60% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/µmol.

The Arabidopsis SYN1 cohesin protein is required for sister chromatid arm cohesion and homologous chromosome pairing.

The faithful transmission of chromosomes during mitosis and meiosis requires the establishment and subsequent release of cohesion between replicated chromosomes. Sister chromatid cohesion is mediated, in large part, by the cohesin complex, which consists of four highly conserved proteins: SMC1, SMC3, SCC1/REC8 and SCC3. Mitotic cohesin complexes contain SSC1, whereas meiotic cohesin complexes contain the related REC8 protein. As part of studies to identify and characterize proteins required for meiosis in plants, we previously identified a putative Arabidopsis REC8 homolog, referred to as syn1. Preliminary cytological studies indicated that syn1 plants exhibit defects in meiotic chromosome cohesion and condensation that result in fragmentation of the chromosomes and the formation of polyads. In the experiments presented here we show that SYN1 encodes a protein that localizes to arms of meiotic chromosomes from approximately meiotic interphase to anaphase I. The protein is not detected at the centromeres or after metaphase I. Furthermore, fluorescence in situ hybridization experiments on microsporocytes from syn1 plants demonstrate that the mutation eliminates arm cohesion as early as interphase, whereas centromere cohesion is maintained until approximately anaphase I. These results indicate that although the main role of SYN1 is in chromosome arm cohesion, it is also important for maintaining cohesion at the centromeres during late stages of meiosis I.