Synthesis and characterization of two known and one new impurities of dolutegravir: In silico evaluation of certain intermediates against SARS CoV-2 O-ribose methyltransferase (OMTase) was written by Garrepalli, Sailaja;Gudipati, Ramesh;Kapavarapu, Ravikumar;Ravindhranath, Kunta;Pal, Manojit. And the article was included in Journal of Molecular Structure in 2023.Recommanded Product: 638-07-3 The following contents are mentioned in the article:
Besides its use against HIV infection the marketed anti-retroviral drug dolutegravir attracted attention as a potential agent against COVID-19 in multiple AI (artificial intelligence) based studies. The synthesis of O-Me ent-dolutegravir was accomplished in three-steps the first one involved the construction of fused 1,3-oxazinane ring. The cleavage of -OEt ether moiety followed by methylation afforded the target compound The second impurity i.e. N-(2,4-difluorobenzyl)-4-methoxy-3-oxobutanamide was synthesized via a multi-step method involving sequentially the keto group protection, ester hydrolysis, acid chloride formation followed by the reaction with amine and finally keto group deprotection. The synthesis of new or dimer impurity was carried out via another multi-step method similar to the previous one starting from Et 4-chloro acetoacetate. The methodol. involved preparation of ether derivative, keto group protection, ester hydrolysis, preparation of amide derivative via acid chloride formation in situ and then keto group deprotection for a longer duration. The last step afforded the target compound for which a plausible reaction mechanism has been proposed. The in silico evaluation of three selected synthesized intermediates e.g. I, II and III (structurally similar to dolutegravir) against SARS CoV-2 O-ribose methyltransferase (OMTase) (PDB: 3R24) indicated that compound I could be of interest as a possible inhibitor of this protein. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Recommanded Product: 638-07-3).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. Organochlorines stimulate the central nervous system and cause convulsions, tremor, nausea, and mental confusion. Examples are dichlorodiphenyltrichloroethane (DDT), chlordane, lindane, endosulfan, and dieldrin. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Recommanded Product: 638-07-3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics