A formal total synthesis of fusidic acid

Dauben, William G.; Kessel, Carl R.; Kishi, M.; Somei, Masanori; Tada, Mizuki; Guillerm, D.

doi:10.1021/ja00365a063

Cited by 24 publications

(18 citation statements)

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“…Since they have no cross resistance to commonly used antibiotics, chemical derivatization of fusidane-type antibiotics has been extensively carried out aiming at finding more potent analogues 7. , 8. , 9.…”

Section: Discussionmentioning

confidence: 99%

“…Fusidane-type antibiotics have been subjected to extensive chemical synthesis and derivatization 7. , 8. , 9.…”

Section: Introductionmentioning

confidence: 99%

“…As fusidane-type antibiotics are the only known antibiotics that target elongation factor EF-G to inhibit bacterial protein synthesis4., 5., they have no cross-resistance with commonly used antibiotics, which have drawn much attention in the increasing threat of antimicrobial resistance 6 . Fusidane-type antibiotics have been subjected to extensive chemical synthesis and derivatization7., 8., 9., 10., however, more potent analogues than fusidic acid have not been found thus far. Combinational biosynthesis is an alternative approach to generate chemical diversity, which however requires a deep understanding of the biosynthesis of target compounds.

Figure 1Representative fusidane-type antibiotics and gene cluster comparison between fusidic acid and helvolic acid.…”

Section: Introductionmentioning

confidence: 99%

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Biosynthesis of clinically used antibiotic fusidic acid and identification of two short-chain dehydrogenase/reductases with converse stereoselectivity

Cao

et al. 2019

Acta Pharmaceutica Sinica B

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Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid ( fus cluster). This gene cluster consists of eight genes, among which six are conserved in the helvolic acid gene cluster except fusC1 and fusB1 . Introduction of the two genes into the Aspergillus oryzae NSAR1 expressing the conserved six genes led to the production of fusidic acid. A stepwise introduction of fusC1 and fusB1 revealed that the two genes worked independently without a strict reaction order. Notably, we identified two short-chain dehydrogenase/reductase genes fusC1 and fusC2 in the fus cluster, which showed converse stereoselectivity in 3-ketoreduction. This is the first report on the biosynthesis and heterologous expression of fusidic acid.

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Section: Discussionmentioning

confidence: 99%

“…Fusidane-type antibiotics have been subjected to extensive chemical synthesis and derivatization 7. , 8. , 9.…”

Section: Introductionmentioning

confidence: 99%

Figure 1Representative fusidane-type antibiotics and gene cluster comparison between fusidic acid and helvolic acid.…”

Section: Introductionmentioning

confidence: 99%

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Biosynthesis of clinically used antibiotic fusidic acid and identification of two short-chain dehydrogenase/reductases with converse stereoselectivity

Cao

et al. 2019

Acta Pharmaceutica Sinica B

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“…39 The following papers deal with saponins and prosapogenins which are based on known triterpenoids of the following groups: fusidane-lanostane, 40 dammarane-uphane, 41 oleanane,l4*~ 143a ~r s a n e , '~~ and serratane.lU…”

Section: Triterpenoid Saponinsmentioning

confidence: 99%

Triterpenoids

Boar¹

1984

Nat. Prod. Rep.

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“…It is the most potent member of this group and is, to date, the only representative to have been used clinically [ 2 ]. It was first isolated fermentatively in the early 1960s from the fungus Fusidium coccineum [ 3 ], with the description of a complete chemical synthesis following some 20 years later [ 4 ]. FA is mainly used in the treatment of Gram-positive bacterial infections (e.g., infected atopic dermatitis, Figure 1(b) ), particularly those caused by Staphylococcus species [ 2 , 5 , 6 ], and functions by binding to prokaryotic elongation factor G (EF-G), effectively stalling the elongation step of bacterial protein synthesis [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in Commercial Sources of Fusidic Acid: A Comparative Study of the In Vitro Release Characteristics of Forms I and III from a Marketed Pharmaceutical Cream

Byrne¹,

Reinhardt²,

Velasco‐Torrijos

2017

Journal of Analytical Methods in Chemistry

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A comparison of the polymorphic forms of 3 commercial sources of fusidic acid using FTIR and XRPD techniques has been performed in this study. It has been demonstrated that polymorphic Forms I and III are currently available on the commercial market. The influence of the observed polymorphism on the stability of the drug substance in bulk form has been investigated through stability and stress testing according to current ICH guidelines. Significant differences were detected between commercial sources with regard to the stability of the bulk substance under photolytic and humidity stress conditions. When properly packaged in an inert atmosphere, fusidic acid from all 3 manufacturers showed a comparable stability. The effects of the observed polymorphic differences on the intrinsic dissolution rate of the drug substance and its in vitro release from the marketed drug product Fusicutan® plus Betamethasone cream have been investigated. Results indicated that the release rate of the drug substance is similar for polymorphic Forms I and III, allowing both forms to be used during manufacture without affecting the safety or efficacy of the drug product.

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A formal total synthesis of fusidic acid

Cited by 24 publications

References 1 publication

Biosynthesis of clinically used antibiotic fusidic acid and identification of two short-chain dehydrogenase/reductases with converse stereoselectivity

Biosynthesis of clinically used antibiotic fusidic acid and identification of two short-chain dehydrogenase/reductases with converse stereoselectivity

Triterpenoids

Polymorphism in Commercial Sources of Fusidic Acid: A Comparative Study of the In Vitro Release Characteristics of Forms I and III from a Marketed Pharmaceutical Cream

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