Spiropiperidine Sultam and Lactam Templates: Diastereoselective Overman Rearrangement and Metathesis followed by NH Arylation

Martinez‐Alsina, Luis; Murray, John C.; Buzon, Leanne; Bundesmann, Mark W.; Young, Joseph M.; O’Neill, Brian T.

doi:10.1021/acs.joc.7b02096

Cited by 14 publications

(8 citation statements)

References 49 publications

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“…Compounds 10f, 10h, 10i, 10j, 10l, 10m, 10o, 10r, 10t and 10u were synthesised as in literature 31,32 . The remaining compounds were synthesised as follows:…”

Section: Synthesis Of Compounds 10f $ Umentioning

confidence: 99%

Synthesis, biological activities and docking studies of pleuromutilin derivatives with piperazinyl urea linkage

Zhang

Xie

Liu

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Antibiotics resistance is becoming increasingly common, involving almost all antibiotics on the market. Diseases caused by drug resistant bacteria, such as MRSA, have high mortality and negatively affect public health. The development of new drugs would be an effective means of solving this problem. Modifications based on bioactive natural products could greatly shorten drug development time and improve success rate. Pleuromutilin, a natural product from the basidiomycete bacterial species, is a promising antibiotic candidate. In this study, a series of novel pleuromutilin derivatives possessing piperazinyl urea linkage were efficiently synthesised, and their antibacterial activities and bactericidal properties were evaluated via MIC, MBC and Time-kill kinetics assays. The results showed that all compounds exhibited potent activities against tested strains, especially MRSA strains with MIC values as low as 0.125 lg/mL; 8 times lower than that of marketed antibiotic Tiamulin. Docking studies indicate substituted piperazinyl urea derivatives could provide hydrogen bonds and initiate p-p stacking between molecules and surrounding residues.

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“…Compounds 10f, 10h, 10i, 10j, 10l, 10m, 10o, 10r, 10t and 10u were synthesised as in literature 31,32 . The remaining compounds were synthesised as follows:…”

Section: Synthesis Of Compounds 10f $ Umentioning

confidence: 99%

Synthesis, biological activities and docking studies of pleuromutilin derivatives with piperazinyl urea linkage

Zhang

Xie

Liu

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Synthesis of 2-thia-1,8-diazaspiro[4.5]decane 2,2-dioxide. [89] Analogously to the case of fused γ-sultams 40 (Scheme 16), [48] the C α -C β bond formation via the Claisen-type CSIC reaction of N-mesylated amino esters 142 was efficient for synthesis of homologous spirocyclic counterparts 143 in 85-91 % yield (Scheme 49). [90,91] Scheme 49.…”

Section: Eurjocmentioning

confidence: 99%

Saturated Bicyclic Sultams

et al. 2020

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Saturated bicyclic sultams represent a promising class of sp 3-rich three-dimensional scaffolds of outmost importance to organic and medicinal chemistry. In this review with 99 references, synthesis, properties, and applications of these compounds are surveyed. The literature data are categorized according to the structural types (i.e. fused, bridged, and spirocyclic compounds), as well as homologous series

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“…An alternative approach to the 4-spiropiperidine BACE-1 aspartyl protease target 118 was reported by Martinez-Alsina in 2017. 43 Amine 116 was accessed through a diastereoselective Overman rearrangement of trichloroacetimidate 115 followed by DIBAL-H reduction of the resultant trichloroacetamide (Scheme 32). Acylation of amine 116 with acroloyl chloride gave diene 117 which underwent ring closing metathesis to give 4-spiropiperidine 118 in high yield.…”

Section: -Spiropiperidine Formation On a Preformed Piperidine Ringmentioning

confidence: 99%

Strategies for the synthesis of spiropiperidines – a review of the last 10 years

2018

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Spiropiperidines have gained in popularity in drug discovery programmes as medicinal chemists explore new areas of three-dimensional chemical space. This review focuses on the methodology used for the construction of 2-, 3- and 4-spiropiperidines, covering the literature from the last 10 years. It classifies the synthesis of each of the types of spiropiperidine by synthetic strategy: the formation of the spiro-ring on a preformed piperidine ring, and the formation of the piperidine ring on a preformed carbo- or heterocyclic ring. While 3- and 4-spiropiperidines are predominantly synthesised for drug discovery projects, 2-spiropiperidines are synthesised en route to natural products. The lack of 2-spiropiperidines in drug discovery is presumably due to limited general procedures for their synthesis.

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Spiropiperidine Sultam and Lactam Templates: Diastereoselective Overman Rearrangement and Metathesis followed by NH Arylation

Cited by 14 publications

References 49 publications

Synthesis, biological activities and docking studies of pleuromutilin derivatives with piperazinyl urea linkage

Synthesis, biological activities and docking studies of pleuromutilin derivatives with piperazinyl urea linkage

Saturated Bicyclic Sultams

Strategies for the synthesis of spiropiperidines – a review of the last 10 years

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