Process Investigations on the One-Pot Synthesis of Rifamycin S Avoiding Chlorinated Solvents

Abstract

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.

The Impact of Linker Length on P450 Fusion Constructs: Activity, Stability and Coupling

“…[21,22] In synthetic chemistryt he hydroxylation is limitedb yh arsh reaction conditions and low regioselectivities, in particular for terminal positions. [23] To use an efficient biocatalytic system for this application-with chemical knowledge [24,25] -is therefore of great interest.…”

Modifications, biological origin and antibacterial activity of naphthalenoid ansamycins

“…9 and 37) is capable of inhibiting bacterial RNAPs and is derived from natural rifamycin S, for which further natural transformations, especically those yielding rifamycin O, are mediated by transketolase Rif15 and the cytochrome P450 enzyme Rif16. [127][128][129][130] High antibiotic activities of clinically-used 107, against both Gram-positive and Gram-negative bacteria, created opportunity to produce alternatives relative to 69 and encouraged further exploration of semisynthetic transformations of iminoquinone ansamycins, assigned to the 4-iminonaphthalen-1(4H)-one-C 17 group (Fig. 2).…”

Drug Syntheses Beyond the Rule of 5

“…Just as in the preparation of rifamycins 32 and 33 , functionalisation at C‐3 of the aromatic moiety of rifamycin B ( 31 ) is the key step in the synthesis of rifabutin ( 34 , Scheme ). First, conversion of rifamycin B ( 31 ) to rifamycin S ( 40 ) was performed using ammonium persulfate in methanol, then sodium azide was used for introduction of the amino group to give 41 . Compound 41 was then converted to imine 42 upon treatment with ammonia before condensation with ketone 43 to give rifabutin 34 …”