- A FACILE PREPARATION OF RIFAMYCIN DERIVATIVES BY USE OF MANGANESE DIOXIDE
-
Rifamycin O, rifamycin S and rifamycin SV were prepared in good yields (88-94percent) by the oxidation and hydrolytic cleavage of rifamycin B in the presence of manganese dioxide.
- Seong, Baik Lin,Han, Moon Hi
-
-
Read Online
- Deciphering the late steps of rifamycin biosynthesis
-
Rifamycin-derived drugs, including rifampin, rifabutin, rifapentine, and rifaximin, have long been used as first-line therapies for the treatment of tuberculosis and other deadly infections. However, the late steps leading to the biosynthesis of the industrially important rifamycin SV and B remain largely unknown. Here, we characterize a network of reactions underlying the biosynthesis of rifamycin SV, S, L, O, and B. The two-subunit transketolase Rif15 and the cytochrome P450 enzyme Rif16 are found to mediate, respectively, a unique C-O bond formation in rifamycin L and an atypical P450 ester-to-ether transformation from rifamycin L to B. Both reactions showcase interesting chemistries for these two widespread and well-studied enzyme families.
- Qi, Feifei,Lei, Chao,Li, Fengwei,Zhang, Xingwang,Wang, Jin,Zhang, Wei,Fan, Zhen,Li, Weichao,Tang, Gong-Li,Xiao, Youli,Zhao, Guoping,Li, Shengying
-
-
- Highly Efficient Synthesis of a Staphylococcus aureus Targeting Payload to Enable the First Antibody–Antibiotic Conjugate
-
A practical synthesis of the complex payload for an anti-Staphylococcus aureus THIOMABTM antibody–antibiotic conjugate (TAC) is described. The route takes advantage of a delicate oxidative condensation, achieved using a semi-continuous flow procedure. It allows for the generation of kilogram quantities of a key intermediate to enable a mild nucleophilic aromatic substitution to the tertiary amine free drug. The linker component is introduced as a benzylic chloride, which allows formation of the quaternary ammonium salt linker-drug. This chemical process surmounts numerous synthetic challenges and navigates deeply colored and unstable compounds to support clinical studies to counter S. aureus bacterial infections.
- Linghu, Xin,Segraves, Nathaniel L.,Abramovich, Ifat,Wong, Nicholas,Müller, Barbara,Neubauer, Nadja,Fantasia, Serena,Rieth, Sebastian,Bachmann, Stephan,Jansen, Michael,Sowell, C. Gregory,Askin, David,Koenig, Stefan G.,Gosselin, Francis
-
supporting information
p. 2837 - 2840
(2018/03/01)
-
- Process Investigations on the One-Pot Synthesis of Rifamycin S Avoiding Chlorinated Solvents
-
The facile synthesis of rifamycin S from rifamycin B, a member of the ansamycin family of antibiotics, via the oxidation of rifamycin B was developed. Currently on an industrial scale, this oxidation is performed using harsh pH conditions and chlorinated solvents. With the development of a suitable buffer/methanol system, a similar yield and space-time-yield in comparison to the current process can be obtained renouncing chlorinated solvents. Employment of methanol as a reaction medium in this process is crucial for attaining high yields under mild reaction conditions. With this method a space-time-yield of 189 g L-1 h-1 of rifamycin S was achieved in one step.
- L?w, Sebastian A.,Nestl, Bettina M.,Weissenborn, Martin J.,Zepeck, Ferdinand,Hauer, Bernhard
-
supporting information
p. 1544 - 1547
(2015/12/01)
-
- Process for preparing rifamycin S by hydrolysis of rifamycin O
-
A process for preparing rifamycin S from rifamycin O. Rifamycin O is dissolved in a mixture of an organic solvent and an alcohol at room temperature. The rifamycin O is then hydrolyzed with a mineral acid and the thus obtained rifamycin S is purified by crystallization.
- -
-
-