PMC:7571312 / 13041-13941 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7571312","sourcedb":"PMC","sourceid":"7571312","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7571312","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.","tracks":[{"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"}],"attributes":[{"subj":"T64601","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T24049","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T15952","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T58065","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T75772","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T70942","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T27962","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T47002","pred":"source","obj":"LitCovid-PD-CLO"},{"subj":"T84592","pred":"source","obj":"LitCovid-PD-CLO"}]},{"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"},{"subj":"T198","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T199","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T200","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T202","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T203","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T204","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T205","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T207","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T209","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T211","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T212","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T213","pred":"source","obj":"LitCovid-PD-CHEBI"},{"subj":"T214","pred":"source","obj":"LitCovid-PD-CHEBI"}]},{"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#"}],"attributes":[{"subj":"T68","pred":"source","obj":"LitCovid-sentences"},{"subj":"T69","pred":"source","obj":"LitCovid-sentences"},{"subj":"T70","pred":"source","obj":"LitCovid-sentences"},{"subj":"T71","pred":"source","obj":"LitCovid-sentences"},{"subj":"T72","pred":"source","obj":"LitCovid-sentences"}]},{"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"},{"subj":"354","pred":"source","obj":"LitCovid-PubTator"},{"subj":"355","pred":"source","obj":"LitCovid-PubTator"},{"subj":"356","pred":"source","obj":"LitCovid-PubTator"},{"subj":"357","pred":"source","obj":"LitCovid-PubTator"},{"subj":"358","pred":"source","obj":"LitCovid-PubTator"},{"subj":"359","pred":"source","obj":"LitCovid-PubTator"},{"subj":"360","pred":"source","obj":"LitCovid-PubTator"},{"subj":"361","pred":"source","obj":"LitCovid-PubTator"},{"subj":"362","pred":"source","obj":"LitCovid-PubTator"},{"subj":"363","pred":"source","obj":"LitCovid-PubTator"}],"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_"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"LitCovid-PD-CLO","color":"#93eaec","default":true},{"id":"LitCovid-PD-CHEBI","color":"#ecd393"},{"id":"LitCovid-sentences","color":"#b993ec"},{"id":"LitCovid-PubTator","color":"#93ec9f"}]}]}}