Abstract:The synthesis and structure-activity relationships of 7-[D-a-amino-a-(4-hydroxyphenyl)-acetamido]-3-[(Z)-l-propenyl]-3-cephem-4-carboxylic acid (BMY-28100) and its analogs in the 3-and 7-side chains are described. The 3-(substituted-propenyl) groups were introduced by the Wittig reaction of the 3-phosphoniomethyl cephems which were derived from the 3-chloromethyl derivatives. The reaction gave predominantly the cis isomer regarding the 3-side chain. The cis and trans isomers showed characteristic UV and 1H NMR… Show more
“…Moreover, a 45-fold rate enhancement was observed when lactam 3 was coupled with vinyltributylstannane in the presence of the tri-2furylphosphine catalyst system. 1 In a related study 26 aimed at developing an efficient synthesis of antibiotic BMY-28100, 27 Farina showed that the beneficial effects observed upon substitution of TFP for PPh 3 in the Stille reaction may be of general scope. Treatment of vinyl triflate 9 with a variety of organostannanes at room temperature in NMP using ZnCl 2 and the TFP catalyst system smoothly afforded the desired cross-coupled products 10-12 in moderate to excellent yields 28 (Scheme 3).…”
Section: A Discovery Of Tfp As An Exceptional Ligand For the Stille R...mentioning
Pyridinium counter-ions are an old class of compounds in which the N-protonated pyridine can form hydrogen bonds with different anions, such as tetrachloroferrate. In the past, they have been studied as potential single molecule magnets and normally exhibit antiferromagnetic coupling at very low temperatures (< 10 K). Inspired by the last ACA meeting (2016) where the Cahill group demonstrated that 4-bromo-pyridine could be used as linear linker in crystal engineering, we explored the use of pyridinium tetrachlorometalates to coordinate organic ligands such as N-2-pyridylimidoyl-2-pyridylamidine (1) and N-2-pyrimidylimidoyl-2-pyrimidylamidine (2). This resulted in four complexes of 1 and 2 with the metal in a different coordination site than previous reports. Subsequently, pyridinium tetrachloroferrate(III), pyridinium trichloromanganate(II) monohydrate, and dipyridinium tetrachlorocobaltate(II) were reproduced, along with the new compounds dipyridinium tetrachloroferrate(II) (3), 2,6-diaminopyridinium tetrachloromanganate(II) monohydrate (4) and 2,6-diaminopyridinium tetrachlorocobaltate(II) (5). The unit cell of 3 indicates that it is a polymorph of other similar dipyridinium tetrachlorometalates with the refcodes EWAXIJ, PYDMNC and WOHFII. The crystal structure of 5 exhibits strong intermolecular interactions between the cation and the tetrachlocobaltate(II) anions, in which each 2,6-diaminopyridinium cations are coordinating to the tetrachlorocobaltate in a pincer-like fashion consisting of three hydrogen bonds, two in the amino groups and one in the protonated pyridine. The results of these studies will be presented, as well as our efforts towards exploration of these pyridinium counterions in the synthesis of metallic complexes with various organic ligands in the pursuit of metallic clusters.
“…Moreover, a 45-fold rate enhancement was observed when lactam 3 was coupled with vinyltributylstannane in the presence of the tri-2furylphosphine catalyst system. 1 In a related study 26 aimed at developing an efficient synthesis of antibiotic BMY-28100, 27 Farina showed that the beneficial effects observed upon substitution of TFP for PPh 3 in the Stille reaction may be of general scope. Treatment of vinyl triflate 9 with a variety of organostannanes at room temperature in NMP using ZnCl 2 and the TFP catalyst system smoothly afforded the desired cross-coupled products 10-12 in moderate to excellent yields 28 (Scheme 3).…”
Section: A Discovery Of Tfp As An Exceptional Ligand For the Stille R...mentioning
Pyridinium counter-ions are an old class of compounds in which the N-protonated pyridine can form hydrogen bonds with different anions, such as tetrachloroferrate. In the past, they have been studied as potential single molecule magnets and normally exhibit antiferromagnetic coupling at very low temperatures (< 10 K). Inspired by the last ACA meeting (2016) where the Cahill group demonstrated that 4-bromo-pyridine could be used as linear linker in crystal engineering, we explored the use of pyridinium tetrachlorometalates to coordinate organic ligands such as N-2-pyridylimidoyl-2-pyridylamidine (1) and N-2-pyrimidylimidoyl-2-pyrimidylamidine (2). This resulted in four complexes of 1 and 2 with the metal in a different coordination site than previous reports. Subsequently, pyridinium tetrachloroferrate(III), pyridinium trichloromanganate(II) monohydrate, and dipyridinium tetrachlorocobaltate(II) were reproduced, along with the new compounds dipyridinium tetrachloroferrate(II) (3), 2,6-diaminopyridinium tetrachloromanganate(II) monohydrate (4) and 2,6-diaminopyridinium tetrachlorocobaltate(II) (5). The unit cell of 3 indicates that it is a polymorph of other similar dipyridinium tetrachlorometalates with the refcodes EWAXIJ, PYDMNC and WOHFII. The crystal structure of 5 exhibits strong intermolecular interactions between the cation and the tetrachlocobaltate(II) anions, in which each 2,6-diaminopyridinium cations are coordinating to the tetrachlorocobaltate in a pincer-like fashion consisting of three hydrogen bonds, two in the amino groups and one in the protonated pyridine. The results of these studies will be presented, as well as our efforts towards exploration of these pyridinium counterions in the synthesis of metallic complexes with various organic ligands in the pursuit of metallic clusters.
“…The cleavage of the acetyl residue can be carried out both enzymatically [241] and chemically [242] under mild conditions. Oxidation of alcohols obtained in this way allows preparation of the corresponding 3-formylcephalosporins, which can suffer further transformations such as the Wittig olefination [243] or Barbier-type allylation [244]. 3-Halomethyl cephalosporins can be synthesized via substitution reactions in 3-acetoxy(hydroxy)methyl cephalosporins [245].…”
Section: Reactions For the Transformation Of Functional Groups In Sidmentioning
The large number of recent reports on b-lactam chemistry demonstrates the increasing interest in this important class of compounds. Monocyclic b-lactams frequently serve as precursors for the synthesis of classical bicyclic b-lactam antibiotics. The cyclic 2-azetidinone skeleton has been extensively used as a template on which to build the heterocyclic structure fused to the four-membered ring, using the chirality and functionalization of the b-lactam nucleus as a stereocontrolling element. The discovery of nonclassical b-lactam antibiotics, such as monobactams and nocardicins, coupled with ever-growing new applications such as enzyme inhibition has triggered a renewed interest in the building of new monocyclic b-lactam derivatives. Besides the utility of b-lactams as biologically active agents, they are used as intermediates in a-and b-amino acid synthesis, as well as building blocks for alkaloids, heterocycles, taxoids and other types of compounds of biological and medicinal interest.
Physicochemical Data
Computational ChemistryTheoretical studies show that b-lactams are weaker bases, in the gas phase, than acyclic amides [1]. The attenuation of basicity upon cyclization is stronger than that found for cyclic ketones of similar size due to the existence of a negative hyperconjugation effect that is present in b-lactams but not in cyclic ketones. Ab initio calculations indicate that both b-lactams and acyclic amides are oxygen bases, but the gap between the oxygen and nitrogen intrinsic basicities is much smaller in the former due to the aforementioned cyclization effects. This decrease of the oxygen Modern Heterocyclic Chemistry, First Edition. Edited
“…In another pioneering paper S. Boettger described the development of a Zymark Py Technology automated system for process optimisation . After having established the robotics system their first test reaction was a room-temperature reaction which is used in the synthesis of a wide variety of oral cephalosporin antibiotics (Scheme ). 2 Phosphine reaction…”
Section: Overview Of Automated Chemistry In Organic Process
Research ...mentioning
An overview of the current methods, available systems, and applications of laboratory automation in chemical process research and development is given. Examples of the successful implementation of automated synthesis into reaction optimisation and process development are discussed.
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