Enantioselective Syntheses of 1-Carbacephalosporins from Chemoenzymically Derived β-Hydroxy-α-Amino Acids: Applications to the Total Synthesis of Carbacephem Antibiotic Loracarbef

Jackson, B.; Pedersen, Steve W; Fisher, Jack W.; Misner, Jerry W.; Gardner, J; Staszak, Michael A.; Doecke, Christopher W.; Rizzo, John Ross; Aikins, James; Farkas, Eugene; Trinkle, Kristina L.; Vicenzi, Jeffrey T.; Reinhard, Matt R.; Kroeff, Eugene P.; Higginbotham, Chris A; Gažák, Radek; Zhang, Tony Y.

doi:10.1016/s0040-4020(00)00416-6

Cited by 26 publications

(11 citation statements)

References 40 publications

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“…In the total synthesis of a carbacephalosporin antibiotic, Eli Lilly had already shown in 1991 the use of Penicillin G Amidase in the pharmaceutical industry. 57, 58 The enzymatic conversion of racemic (2R,3S), (2S,3R)-cis-3-aminoazetidinone was established in the synthesis of (2R,3S)-b-lactam intermediate 1 (Fig. 3) as a key intermediate of Loracarbef, avoiding low yields of the formerly used chemical resolution.…”

Section: Amide Formation Avoiding Poor Atom Economy Reagentsmentioning

confidence: 99%

Industrial biotechnology—the future of green chemistry?

et al. 2011

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Section: Amide Formation Avoiding Poor Atom Economy Reagentsmentioning

confidence: 99%

Industrial biotechnology—the future of green chemistry?

et al. 2011

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“…The syntheses of acids 2f‐h are depicted in Figure . Thus, 4‐pentenoic acid tert‐ butyl ester ( 3 ) was ozonolyzed to give the tert‐ butyl ester of succinic semialdehyde 5 52. Addition of the ylide derived from phosphonium salt 7 53 afforded the ( Z )‐olefin 8a (61%, Z / E > 95:5).…”

Section: Chemistrymentioning

confidence: 99%

Improving the Antitumor Activity of Squalenoyl‐Paclitaxel Conjugate Nanoassemblies by Manipulating the Linker between Paclitaxel and Squalene

Caron¹,

Maksimenko²,

Wack³

et al. 2012

Adv Healthcare Materials

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A series of new lipid prodrugs of paclitaxel, which can be formulated as nanoassemblies, are described. These prodrugs which are designed to overcome the limitations due to the systemic toxicity and low water solubility of paclitaxel consist of a squalene chain bound to the 2'-OH of paclitaxel through a 1,4-cis,cis-dienic linker. This design allows the squalene-conjugates to self-assemble as nanoparticular systems while preserving an efficient release of the free drug, thanks to the dienic spacer. The size, steric hindrance, and functional groups of the spacer have been modulated. All these prodrugs self-assemble into nanosized aggregates in aqueous solution as characterized by dynamic light scattering and transmission electron microscopy and appear stable in water for several days as determined by particle size measurement. In vitro biological assessment shows that these squalenoyl-paclitaxel nanoparticles display notable cytotoxicity on several tumor cell lines including A549 lung cell line, colon cell line HT-29, or KB 3.1 nasopharyngeal epidermoid cell line. The cis,cis-squalenyl-deca-5,8-dienoate prodrug show improved activity over simple 2'-squalenoyl-paclitaxel prodrug highlighting the favourable effect of the dienic linker. The antitumor efficacy of the nanoassemblies constructed with the more active prodrugs has been investigated on human lung (A549) carcinoma xenograft model in mice. The prodrug bearing the cis,cis-deca-5,8-dienoyl linker shows comparable antitumor efficacy to the parent drug, but reveals a much lower subacute toxicity as seen in body weight loss. Thus, nanoparticles with the incorporated squalenoyl paclitaxel prodrug may prove useful for replacement of the toxic Cremophor EL.

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“…The enzyme load was rather high (15% w/w), and the isolation required elution from an SP207 resin column. The experimental description of a medium-scale aldol reaction is given (>120 g product) 128 …”

Section: 4 Asymmetric C−c Bond Formationmentioning

confidence: 99%

“…Sharpless' titanium tartrate-catalyzed asymmetric epoxidation (SAE) is a method of choice for the epoxidation of allylic alcohols . Consistently high enantioselectivities are observed for nearly all substitution patterns of the substrate, and a multitude of subsequent transformations are amenable to the epoxy alcohol products.…”

Section: 52 Asymmetric Epoxidation Of Alkenesmentioning

confidence: 99%