Palladium-Catalyzed Direct C-3 Alkynylation of Indolizines with (2,2-Dibromovinyl)arenes

<div><p></p><p>The direct C-3 alkynylation of indolizines with (2,2-dibromovinyl)arenes in the presence of palladium catalyst has been developed. This novel protocol showed wide substrate scope with respect to both indolizines and dibromoalkenes. Also this method was characterized with high efficiency and good functional group tolerance.</p> </div

Nickel-Catalyzed Stereoselective Alkenylation of C(sp³)–H Bonds with Terminal Alkynes

A nickel-catalyzed stereoselective alkenylation of an unactivated β-C­(sp³)–H bond in aliphatic amide with terminal alkynes using 8-aminoquinoline auxiliary is reported for the first time. This reaction displays excellent functional group tolerance with respect to both aliphatic amides and terminal alkynes and features a cheap nickel catalytic system. The 8-aminoquinolyl directing group could be smoothly removed, and the resultant β-styrylcarboxylic acid derivatives could serve as versatile building blocks for further transformation

Image_3_Case report: Two pediatric cases of long-term leukemia-free survival with relapsed acute T-lymphoblastic leukemia treated with donor CD7 CAR-T cells bridging to haploidentical stem cell transplantation.jpeg

IntroductionPatients with relapsed/refractory (r/r) acute T-lymphoblastic leukemia (T-ALL) have a poor prognosis. We developed donor CD7 chimeric antigen receptor T (CAR-T) cells to salvage r/r T-ALL patients and obtained encouraging results. Patients who had not received allogeneic (allo-) hematopoietic stem cell transplantation (HSCT) before CAR-T therapy would develop pancytopenia and immunodeficiency for a long period after CD7 CAR-T therapy; therefore, allo-HSCT is needed in these patients. Here, we report two pediatric r/r T-ALL patients who received donor CD7 CAR-T bridging to allo-HSCT with leukemia-free survival (LFS) and sustained negative minimal residual disease for >2 years.Case presentationPatient 1 was a 10-year-old boy who visited our hospital because of a T-ALL relapse with multiple lymphadenopathies without discomfort. The patient did not achieve remission after one course of induction chemotherapy. The patient then received donor (his father) CD7 CAR-T cells and achieved complete remission (CR). Thirty days after the first CAR-T cell infusion, he received allo-HSCT, and his father was also the donor. His LFS was >3 years. Patient 2 was an 8-year-old boy who was admitted to our hospital with relapsed T-ALL with fever, cough, and mild dyspnea. He did not achieve remission after one course of induction chemotherapy; therefore, he received donor (his father) CD7 CAR-T cells and achieved CR. Twenty-six days after CAR-T cell infusion, the patient received allo-HSCT, with his father as the donor. He has survived for >2 years free of leukemia. At the last follow up, both patients were alive and presented a good quality of lifeConclusionThe long-term survival of these two patients supports the use of CD7 CAR-T therapy bridging to allo–HSCT as an effective and safe treatment with the capacity to make r/r T-ALL a curable disease, similar to r/r acute B-lymphoblastic leukemia.</p

Cobalt-Catalyzed Oxidant-Free Spirocycle Synthesis by Liberation of Hydrogen

The first example of oxidant-free cobalt-catalyzed synthesis of five-membered spirocycles is reported from benzimidates and maleimides utilizing nitrobenzene as promoter. In contrast to previously known cobalt-catalyzed oxidative C–H functionalization reactions, this transformation occurs efficiently in the absence of oxidant and is accompanied by liberation of hydrogen. The spiro-lactams were readily achieved by the hydrolysis of as-prepared spirocyclic compounds. The Cp*Rh­(III) catalyst shows poor reactivity

Cobalt-Catalyzed Oxidant-Free Spirocycle Synthesis by Liberation of Hydrogen

The first example of oxidant-free cobalt-catalyzed synthesis of five-membered spirocycles is reported from benzimidates and maleimides utilizing nitrobenzene as promoter. In contrast to previously known cobalt-catalyzed oxidative C–H functionalization reactions, this transformation occurs efficiently in the absence of oxidant and is accompanied by liberation of hydrogen. The spiro-lactams were readily achieved by the hydrolysis of as-prepared spirocyclic compounds. The Cp*Rh­(III) catalyst shows poor reactivity

Cu(II)-Promoted Palladium-Catalyzed C–H Ortho-Arylation of <i>N</i>,<i>N</i>‑Dimethylbenzylamines

A novel protocol for palladium-catalyzed arylation of the C­(sp²)–H bond directed by a <i>N</i>,<i>N</i>-dimethylaminomethyl group in the presence of AgOAc and Cu­(OAc)₂·H₂O is described. Various aryl iodides proved to be efficient coupling partners, furnishing the corresponding ortho monoarylated or diarylated arenes in moderate to good yields. Cu­(OAc)₂·H₂O is found to be the important additive to improve the yields in this transformation

Image_1_Case report: Two pediatric cases of long-term leukemia-free survival with relapsed acute T-lymphoblastic leukemia treated with donor CD7 CAR-T cells bridging to haploidentical stem cell transplantation.png

IntroductionPatients with relapsed/refractory (r/r) acute T-lymphoblastic leukemia (T-ALL) have a poor prognosis. We developed donor CD7 chimeric antigen receptor T (CAR-T) cells to salvage r/r T-ALL patients and obtained encouraging results. Patients who had not received allogeneic (allo-) hematopoietic stem cell transplantation (HSCT) before CAR-T therapy would develop pancytopenia and immunodeficiency for a long period after CD7 CAR-T therapy; therefore, allo-HSCT is needed in these patients. Here, we report two pediatric r/r T-ALL patients who received donor CD7 CAR-T bridging to allo-HSCT with leukemia-free survival (LFS) and sustained negative minimal residual disease for >2 years.Case presentationPatient 1 was a 10-year-old boy who visited our hospital because of a T-ALL relapse with multiple lymphadenopathies without discomfort. The patient did not achieve remission after one course of induction chemotherapy. The patient then received donor (his father) CD7 CAR-T cells and achieved complete remission (CR). Thirty days after the first CAR-T cell infusion, he received allo-HSCT, and his father was also the donor. His LFS was >3 years. Patient 2 was an 8-year-old boy who was admitted to our hospital with relapsed T-ALL with fever, cough, and mild dyspnea. He did not achieve remission after one course of induction chemotherapy; therefore, he received donor (his father) CD7 CAR-T cells and achieved CR. Twenty-six days after CAR-T cell infusion, the patient received allo-HSCT, with his father as the donor. He has survived for >2 years free of leukemia. At the last follow up, both patients were alive and presented a good quality of lifeConclusionThe long-term survival of these two patients supports the use of CD7 CAR-T therapy bridging to allo–HSCT as an effective and safe treatment with the capacity to make r/r T-ALL a curable disease, similar to r/r acute B-lymphoblastic leukemia.</p

Copper-Mediated Aryloxylation and Vinyloxylation of β‑C(sp³)–H Bond of Propionamides with Organosilanes

A novel copper-mediated method for the aryloxylation and vinyloxylation of β-C­(sp³)–H bonds of propioamides with organosilanes is described. The reaction proceeds with the assistance of an 8-aminoquinolyl auxiliary in a tandem way by the first oxidation of β-C­(sp³)–H bonds and subsequent arylation/vinylation to give the aryloxylation/vinyloxylation products. This unusual aryloxy/vinyloxy forming reaction offers a new avenue for the functionalization of unactivated sp³ C–H bonds in organic synthesis

Image_2_Case report: Two pediatric cases of long-term leukemia-free survival with relapsed acute T-lymphoblastic leukemia treated with donor CD7 CAR-T cells bridging to haploidentical stem cell transplantation.jpeg

IntroductionPatients with relapsed/refractory (r/r) acute T-lymphoblastic leukemia (T-ALL) have a poor prognosis. We developed donor CD7 chimeric antigen receptor T (CAR-T) cells to salvage r/r T-ALL patients and obtained encouraging results. Patients who had not received allogeneic (allo-) hematopoietic stem cell transplantation (HSCT) before CAR-T therapy would develop pancytopenia and immunodeficiency for a long period after CD7 CAR-T therapy; therefore, allo-HSCT is needed in these patients. Here, we report two pediatric r/r T-ALL patients who received donor CD7 CAR-T bridging to allo-HSCT with leukemia-free survival (LFS) and sustained negative minimal residual disease for >2 years.Case presentationPatient 1 was a 10-year-old boy who visited our hospital because of a T-ALL relapse with multiple lymphadenopathies without discomfort. The patient did not achieve remission after one course of induction chemotherapy. The patient then received donor (his father) CD7 CAR-T cells and achieved complete remission (CR). Thirty days after the first CAR-T cell infusion, he received allo-HSCT, and his father was also the donor. His LFS was >3 years. Patient 2 was an 8-year-old boy who was admitted to our hospital with relapsed T-ALL with fever, cough, and mild dyspnea. He did not achieve remission after one course of induction chemotherapy; therefore, he received donor (his father) CD7 CAR-T cells and achieved CR. Twenty-six days after CAR-T cell infusion, the patient received allo-HSCT, with his father as the donor. He has survived for >2 years free of leukemia. At the last follow up, both patients were alive and presented a good quality of lifeConclusionThe long-term survival of these two patients supports the use of CD7 CAR-T therapy bridging to allo–HSCT as an effective and safe treatment with the capacity to make r/r T-ALL a curable disease, similar to r/r acute B-lymphoblastic leukemia.</p