Rh-DuPhos-catalyzed asymmetric hydrogenation of alpha,beta-diamidoacrylates provides a highly efficient and enantioselective route to chiral alpha,beta-diaminopropanoic acid derivatives. The mechanistic course of the hydrogenation was studied using isotopically enriched enamide complexes and phosphorus and carbon NMR. Addition of methyl alpha-N-benzoyl-beta-N-acetyl-diaminopropenoate to the solvated catalyst gave a single 1:1 enamide complex and demonstrated the binding of the olefin and alpha-amide carbonyl group; the carboxylate and beta-N-acyl groups did not bind to the metal. Changes to the electronic and steric properties of the beta-N-acyl group were well tolerated; however, small changes to the binding alpha-N-acyl group were found to significantly affect hydrogenation yields.

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This report describes a new convergent, selective, and economical synthesis of DMP 777, 1 ending with the coupling of the chiral -lactam half of the molecule (1) to the chiral amine as the isocyanate (2). Other steps involve the coupling of the -lactam 3 to the phenolic moiety under phase-transfer conditions, followed by resolution of the resulting piperazine derivative using a chiral acid, and recycling of the undesired enantiomer also under phase-transfer conditions. The chiral amine 4 was produced efficiently starting from (R)-r-methylbenzylamine and the corresponding butyrophenone.Contemporary pharmaceuticals often contain multiple chiral centers which provide a significant challenge to the process chemist. Fortunately, an array of tools is now available to address absolute stereochemistry, including classical resolution, chiral auxiliaries, asymmetric catalysis, and enzyme resolution. It is increasingly evident that no single method is consistently superior. A thorough approach to process development requires the consideration of all available chiral technologies to provide the most efficient route to a given drug candidate.DMP 777, an inhibitor of leukocyte elastase, could prevent degradation of the structural proteins elastin and collagen, a process implicated in cystic fibrosis and rheumatoid arthritis. 2 Retrosynthetic analysis indicates that DMP 777 should be accessible by coupling two enantiopure fragments, -lactam 1 and isocyanate 2 (Figure 1). Potentially, -lactam 1 may derive from the commercially available racemic lactam 3. 3 Consequently route-development efforts focused on identifying efficient conditions for elaboration of 3 into racemic 1, and its subsequent resolution. The precursor to isocyanate 2, amine 4, is not an article of commerce; therefore, a process from simple materials had to be devised. We will discuss in turn the synthesis of fragments 1 and 2 and conclude by describing a procedure for their efficient coupling.A short convergent process required a practical synthesis and resolution of the -lactam portion (Scheme 1). The reaction conditions had to be balanced to provide the requisite basic elimination of propionic acid from 3 to give the reactive 3,3-diethylazetin-2-one, 5, without hydrolysis of lactam. Phase-transfer catalytic conditions using a tetrabutylammonium salt gave the most efficient reaction, with an isolated yield of 88%. 4 About 25 chiral acids were screened for utility in the resolution. Diacetoneketogulonic acid (DAG) gave by far the best resolution, with the R-enantiomer DAG salt crystallizing out in high ee and thus overcoming a 10-bond separation between amine group and the chiral center. The S-isomer was then easily precipitated, DAG was recovered, and the R-isomer was racemized under phase-transfer conditions similar to those for its original synthesis (conversion of 3 to 1-racemate). Clarke, G. D. E.; Dowle, M. D.; Harrison, L. A.; Hodgson, S. T.; Inglis, G. G. A.; Johnson, M. R.; Shah, P.; Upton, R. J.; Walls, S. B. J. Org. Chem. 1999, 64, 5166-5175 and ref...

2,3-Diaminobutanoic acid (DAB) is found in several peptide antibiotics, toxins, and biologically active molecules. This paper describes the practical and highly enantioselective synthesis of all four N,N'-protected DAB stereoisomers using an asymmetric Rh(I)-phosphine-catalyzed hydrogenation of isomeric enamides as the key step. Thermal and photochemical isomerization of the enamide hydrogenation substrates coupled with catalyst-geometric isomer pairing allows targeted synthesis of single DAB isomers in maximum yield.

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This article performs an exploratory study of the newly formulated Guidelines for College English Teaching (Draft Exposure)(2015)(Guidelines), aiming at exploring how different the latest Guidelines is from the previous ones, what challenges it brings to teachers and how these challenges can be countered. Therefore, comparisons are made among six syllabi to illustrate the developments college English has achieved and its existent problems as well. To address these problems, Guidelines (2015) is issued with three new features: the integration of instrumentality and humanity, the introduction of intercultural education and the system of multiple curriculum for multiple teaching objectives. Its issuing poses tremendous challenges to college English teachers, of which increasing demands on college English teachers' professional expertise, skillful employment of information technology and academic performance stand out. To help counter these challenges and difficulties, suggestions are made from three levels with the hope that improved teachers' quality can facilitate the implementation of Guidelines (2015) and guarantee the potential achievement of its expected objectives. These suggestions are: life-long learning and self-directed development consciousness, the establishment of teacher education system by faculties and universities and continued governmental support in and favorable policies to college English teacher education.

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A new alkaloid, N-allylnorgalanthamine ( 1), was isolated from the bulbs of LYCORIS GUANGXIENSIS Y. Hsu et Q. J. Fan (Amaryllidaceae). Additionally, seven known alkaloids, lycorine, narwedine, galanthamine, lycoramine, crinine, norgalanthamine, and pseudolycorine were also obtained. The structure of 1 was established through the interpretation of spectral data.