PMC:7571312 / 13041-13941 JSONTXT

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T64601","span":{"begin":128,"end":130},"obj":"http://purl.obolibrary.org/obo/CLO_0008285"},{"id":"T24049","span":{"begin":249,"end":251},"obj":"http://purl.obolibrary.org/obo/CLO_0001302"},{"id":"T15952","span":{"begin":276,"end":277},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T58065","span":{"begin":297,"end":310},"obj":"http://purl.obolibrary.org/obo/UBERON_0002329"},{"id":"T75772","span":{"begin":318,"end":320},"obj":"http://purl.obolibrary.org/obo/CLO_0008285"},{"id":"T70942","span":{"begin":415,"end":417},"obj":"http://purl.obolibrary.org/obo/CLO_0001313"},{"id":"T27962","span":{"begin":451,"end":454},"obj":"http://purl.obolibrary.org/obo/CLO_0002526"},{"id":"T47002","span":{"begin":475,"end":477},"obj":"http://purl.obolibrary.org/obo/CLO_0001000"},{"id":"T84592","span":{"begin":827,"end":829},"obj":"http://purl.obolibrary.org/obo/CLO_0008307"}],"text":"Hydroxymethylketone (HMK) derivatives were accessed by two complimentary approaches illustrated in Scheme 3. Elaboration of the P1′-protected oxygen intermediate 9 by sequential amide bond coupling reactions provided benzylether derivatives such as 34 in moderate yields with a low propensity for epimerization at the P1 center. Hydrogenolytic debenzylation readily afforded the final HMK inhibitors exemplified by 36. Alternatively, fully elaborated CMK derivatives such as 35 were reacted with benzoylformic acid followed by methanolysis to generate HMK final products such as 36.36 Alkylation of the terminal hydroxyl was achieved under microwave-assisted conditions in the presence of silver (I) oxide to afford alkoxymethylketone inhibitors, as illustrated by 37. Using these two synthetic approaches with substitution of P2 and amine capping structural elements provided inhibitors 4 and 38–50."}

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T198","span":{"begin":128,"end":130},"obj":"Chemical"},{"id":"T199","span":{"begin":142,"end":148},"obj":"Chemical"},{"id":"T200","span":{"begin":178,"end":183},"obj":"Chemical"},{"id":"T202","span":{"begin":318,"end":320},"obj":"Chemical"},{"id":"T203","span":{"begin":389,"end":399},"obj":"Chemical"},{"id":"T204","span":{"begin":510,"end":514},"obj":"Chemical"},{"id":"T205","span":{"begin":612,"end":620},"obj":"Chemical"},{"id":"T207","span":{"begin":689,"end":695},"obj":"Chemical"},{"id":"T209","span":{"begin":700,"end":705},"obj":"Chemical"},{"id":"T211","span":{"begin":735,"end":745},"obj":"Chemical"},{"id":"T212","span":{"begin":827,"end":829},"obj":"Chemical"},{"id":"T213","span":{"begin":834,"end":839},"obj":"Chemical"},{"id":"T214","span":{"begin":877,"end":887},"obj":"Chemical"}],"attributes":[{"id":"A198","pred":"chebi_id","subj":"T198","obj":"http://purl.obolibrary.org/obo/CHEBI_60949"},{"id":"A199","pred":"chebi_id","subj":"T199","obj":"http://purl.obolibrary.org/obo/CHEBI_25805"},{"id":"A200","pred":"chebi_id","subj":"T200","obj":"http://purl.obolibrary.org/obo/CHEBI_29337"},{"id":"A201","pred":"chebi_id","subj":"T200","obj":"http://purl.obolibrary.org/obo/CHEBI_32988"},{"id":"A202","pred":"chebi_id","subj":"T202","obj":"http://purl.obolibrary.org/obo/CHEBI_60949"},{"id":"A203","pred":"chebi_id","subj":"T203","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A204","pred":"chebi_id","subj":"T204","obj":"http://purl.obolibrary.org/obo/CHEBI_37527"},{"id":"A205","pred":"chebi_id","subj":"T205","obj":"http://purl.obolibrary.org/obo/CHEBI_29191"},{"id":"A206","pred":"chebi_id","subj":"T205","obj":"http://purl.obolibrary.org/obo/CHEBI_43176"},{"id":"A207","pred":"chebi_id","subj":"T207","obj":"http://purl.obolibrary.org/obo/CHEBI_30512"},{"id":"A208","pred":"chebi_id","subj":"T207","obj":"http://purl.obolibrary.org/obo/CHEBI_9141"},{"id":"A209","pred":"chebi_id","subj":"T209","obj":"http://purl.obolibrary.org/obo/CHEBI_25741"},{"id":"A210","pred":"chebi_id","subj":"T209","obj":"http://purl.obolibrary.org/obo/CHEBI_29356"},{"id":"A211","pred":"chebi_id","subj":"T211","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A212","pred":"chebi_id","subj":"T212","obj":"http://purl.obolibrary.org/obo/CHEBI_33472"},{"id":"A213","pred":"chebi_id","subj":"T213","obj":"http://purl.obolibrary.org/obo/CHEBI_32952"},{"id":"A214","pred":"chebi_id","subj":"T214","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"}],"text":"Hydroxymethylketone (HMK) derivatives were accessed by two complimentary approaches illustrated in Scheme 3. Elaboration of the P1′-protected oxygen intermediate 9 by sequential amide bond coupling reactions provided benzylether derivatives such as 34 in moderate yields with a low propensity for epimerization at the P1 center. Hydrogenolytic debenzylation readily afforded the final HMK inhibitors exemplified by 36. Alternatively, fully elaborated CMK derivatives such as 35 were reacted with benzoylformic acid followed by methanolysis to generate HMK final products such as 36.36 Alkylation of the terminal hydroxyl was achieved under microwave-assisted conditions in the presence of silver (I) oxide to afford alkoxymethylketone inhibitors, as illustrated by 37. Using these two synthetic approaches with substitution of P2 and amine capping structural elements provided inhibitors 4 and 38–50."}

{"project":"LitCovid-sentences","denotations":[{"id":"T68","span":{"begin":0,"end":108},"obj":"Sentence"},{"id":"T69","span":{"begin":109,"end":328},"obj":"Sentence"},{"id":"T70","span":{"begin":329,"end":418},"obj":"Sentence"},{"id":"T71","span":{"begin":419,"end":768},"obj":"Sentence"},{"id":"T72","span":{"begin":769,"end":900},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Hydroxymethylketone (HMK) derivatives were accessed by two complimentary approaches illustrated in Scheme 3. Elaboration of the P1′-protected oxygen intermediate 9 by sequential amide bond coupling reactions provided benzylether derivatives such as 34 in moderate yields with a low propensity for epimerization at the P1 center. Hydrogenolytic debenzylation readily afforded the final HMK inhibitors exemplified by 36. Alternatively, fully elaborated CMK derivatives such as 35 were reacted with benzoylformic acid followed by methanolysis to generate HMK final products such as 36.36 Alkylation of the terminal hydroxyl was achieved under microwave-assisted conditions in the presence of silver (I) oxide to afford alkoxymethylketone inhibitors, as illustrated by 37. Using these two synthetic approaches with substitution of P2 and amine capping structural elements provided inhibitors 4 and 38–50."}

{"project":"LitCovid-PubTator","denotations":[{"id":"354","span":{"begin":0,"end":19},"obj":"Chemical"},{"id":"355","span":{"begin":21,"end":24},"obj":"Chemical"},{"id":"356","span":{"begin":142,"end":148},"obj":"Chemical"},{"id":"357","span":{"begin":178,"end":183},"obj":"Chemical"},{"id":"358","span":{"begin":496,"end":514},"obj":"Chemical"},{"id":"359","span":{"begin":612,"end":620},"obj":"Chemical"},{"id":"360","span":{"begin":689,"end":705},"obj":"Chemical"},{"id":"361","span":{"begin":716,"end":734},"obj":"Chemical"},{"id":"362","span":{"begin":827,"end":829},"obj":"Chemical"},{"id":"363","span":{"begin":834,"end":839},"obj":"Chemical"}],"attributes":[{"id":"A356","pred":"tao:has_database_id","subj":"356","obj":"MESH:D010100"},{"id":"A357","pred":"tao:has_database_id","subj":"357","obj":"MESH:D000577"},{"id":"A358","pred":"tao:has_database_id","subj":"358","obj":"MESH:C012482"},{"id":"A359","pred":"tao:has_database_id","subj":"359","obj":"MESH:D017665"},{"id":"A360","pred":"tao:has_database_id","subj":"360","obj":"MESH:C040225"},{"id":"A362","pred":"tao:has_database_id","subj":"362","obj":"MESH:C020845"},{"id":"A363","pred":"tao:has_database_id","subj":"363","obj":"MESH:D000588"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"Hydroxymethylketone (HMK) derivatives were accessed by two complimentary approaches illustrated in Scheme 3. Elaboration of the P1′-protected oxygen intermediate 9 by sequential amide bond coupling reactions provided benzylether derivatives such as 34 in moderate yields with a low propensity for epimerization at the P1 center. Hydrogenolytic debenzylation readily afforded the final HMK inhibitors exemplified by 36. Alternatively, fully elaborated CMK derivatives such as 35 were reacted with benzoylformic acid followed by methanolysis to generate HMK final products such as 36.36 Alkylation of the terminal hydroxyl was achieved under microwave-assisted conditions in the presence of silver (I) oxide to afford alkoxymethylketone inhibitors, as illustrated by 37. Using these two synthetic approaches with substitution of P2 and amine capping structural elements provided inhibitors 4 and 38–50."}