Comprehensive Summary,Valbenazine(Ingrezza),a potent and highly selective inhibitor of vesicular monoamine transporter type 2(VMAT2)through the active metabolite hydrotetrabenazine(HTBZ),has been approved for the trea...Comprehensive Summary,Valbenazine(Ingrezza),a potent and highly selective inhibitor of vesicular monoamine transporter type 2(VMAT2)through the active metabolite hydrotetrabenazine(HTBZ),has been approved for the treatment of tardive dyskinesia and,very recently,for chorea,which is associated with Huntington's disease.Despite numerous synthetic efforts dedicated to the synthesis of HTBZ,the industrial preparation of valbenazine uses dihydroisoquinoline as a starting material and the chiral resolution of racemic HTBZ derived from ketone reduction.Herein,we present a practical synthesis of HTBZ and valbenazine featuring a highly stereoselective 1,3-dipolar cycloaddition and enzymatic kinetic resolution.The cascade process includes cycloaddition,N—O bond cleavage,and lactamization,which proved to be operationally simple.The allure of the enzymatic resolution developed in this work offers a rapid access toward affording tetrahydroisoquinoline(THIQ)-fused piperidine in the production of medically significant compounds,such as yohimbine and reserpine.展开更多
An effective transition-metal-free catalytic system is developed for aerobic oxidations of alcohols. Using catalytic amount of bromide-bromate coupling, H2SO4, and NaNO2, together with 2,2,6,6-tetramethylpiperidine N-...An effective transition-metal-free catalytic system is developed for aerobic oxidations of alcohols. Using catalytic amount of bromide-bromate coupling, H2SO4, and NaNO2, together with 2,2,6,6-tetramethylpiperidine N-oxyl radical （TEMPO） in the presence of air, various alcohols could be converted into the corresponding aldehydes or ketones in good to excellent isolated yields under mild conditions.展开更多
A concise route to access 5H-imidazo[2,1-a]isoindole heterofused compounds by copper（I）-catalyzed intra- molecular coupling of non-activated aryl bromides with azoles is reported. With CuI as catalyst, 1,10-phenanth...A concise route to access 5H-imidazo[2,1-a]isoindole heterofused compounds by copper（I）-catalyzed intra- molecular coupling of non-activated aryl bromides with azoles is reported. With CuI as catalyst, 1,10-phenanth- roline as ligand, and K3PO4 as base, the reactions of 1-（2-bromobenzyl）-IH-imidazoles in DMF/o-xylene （I ： 1, V ： V） at 145 ℃ afford the corresponding substituted 5H-imidazo[2,1-a]isoindoles in high yields via intramolecu- lar C-arylation.展开更多
基金the National Natural Science Foundation of China(22271194 and 22371295)the Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture(Grant No.XTD 2210)the Science and Technology Commission of Shanghai Municipality(20XD1404700)is greatly appreciated.
文摘Comprehensive Summary,Valbenazine(Ingrezza),a potent and highly selective inhibitor of vesicular monoamine transporter type 2(VMAT2)through the active metabolite hydrotetrabenazine(HTBZ),has been approved for the treatment of tardive dyskinesia and,very recently,for chorea,which is associated with Huntington's disease.Despite numerous synthetic efforts dedicated to the synthesis of HTBZ,the industrial preparation of valbenazine uses dihydroisoquinoline as a starting material and the chiral resolution of racemic HTBZ derived from ketone reduction.Herein,we present a practical synthesis of HTBZ and valbenazine featuring a highly stereoselective 1,3-dipolar cycloaddition and enzymatic kinetic resolution.The cascade process includes cycloaddition,N—O bond cleavage,and lactamization,which proved to be operationally simple.The allure of the enzymatic resolution developed in this work offers a rapid access toward affording tetrahydroisoquinoline(THIQ)-fused piperidine in the production of medically significant compounds,such as yohimbine and reserpine.
基金grants from National Natural Science Foundation of China，Program for Changjiang Scholars and Innovative Research Team in University
文摘An effective transition-metal-free catalytic system is developed for aerobic oxidations of alcohols. Using catalytic amount of bromide-bromate coupling, H2SO4, and NaNO2, together with 2,2,6,6-tetramethylpiperidine N-oxyl radical （TEMPO） in the presence of air, various alcohols could be converted into the corresponding aldehydes or ketones in good to excellent isolated yields under mild conditions.
文摘A concise route to access 5H-imidazo[2,1-a]isoindole heterofused compounds by copper（I）-catalyzed intra- molecular coupling of non-activated aryl bromides with azoles is reported. With CuI as catalyst, 1,10-phenanth- roline as ligand, and K3PO4 as base, the reactions of 1-（2-bromobenzyl）-IH-imidazoles in DMF/o-xylene （I ： 1, V ： V） at 145 ℃ afford the corresponding substituted 5H-imidazo[2,1-a]isoindoles in high yields via intramolecu- lar C-arylation.
