ABSTRACT
Intermolecular functionalization of tertiary C-H bonds to construct fully substituted stereogenic carbon centers represents a formidable challenge: without the assistance of directing groups, state-of-the-art catalysts struggle to introduce chirality to racemic tertiary sp 3 -carbon centers. Direct asymmetric functionalization of such centers is a worthy reactivity and selectivity goal for modern biocatalysis. Here we present an engineered nitrene transferase (P411-TEA-5274), derived from a bacterial cytochrome P450, that is capable of aminating tertiary C-H bonds to provide chiral α-tertiary primary amines with high efficiency (up to 2300 total turnovers) and selectivity (up to >99% enantiomeric excess (e.e.)). The construction of fully substituted stereocenters with methyl and ethyl groups underscores the enzyme's remarkable selectivity. A comprehensive substrate scope study demonstrates the biocatalyst's compatibility with diverse functional groups and tertiary C-H bonds. Mechanistic studies elucidate how active-site residues distinguish between the enantiomers and enable the enzyme to perform this transformation with excellent enantioselectivity.
ABSTRACT
Cyclospora cayetanensis (C. cayetanensis) is a significant pathogen that causes diarrheal illness and causes large foodborne diarrhea outbreaks in the USA and Canada. However, there is currently a lack of published meta-analysis on the prevalence of C. cayetanensis infection in the global population. A real estimation of a disease prevalence should always be done on the basis of studies designed for that purpose. We conducted a comprehensive search of various databases for articles pertaining to the prevalence of C. cayetanensis infection in humans, spanning from the inception of these databases to March 10, 2023. Utilizing a random effects model, we estimated the prevalence of C. cayetanensis infection in humans. Our analysis included a total of 150 datasets sourced from 42 different countries, which were ultimately selected for the final quantitative assessment. The prevalence of C. cayetanensis infection in humans worldwide was estimated to be 3.4 % (5636/166,611). Notably, Africa exhibited the highest prevalence rate at 5.9 % (606/11,068). Further subgroup analysis revealed a significantly higher infection rate in humans residing in low-income countries (7.6 %, 83/921) compared to those in lower-middle-income countries (4.8 %, 3280/48,852), upper-middle-income countries (2.9 %, 2194/99,419), and high-income countries (0.4 %, 79/17,419). The results indicate that the global prevalence of C. cayetanensis infection in humans is relatively low, despite its extensive geographical distribution and children were found to be more susceptible to C. cayetanensis infection compared to those adults. Sensitivity analysis revealed that one study significantly affects the prevalence of C. cayetanensis, which was adjusted to 2.9 % (4017/160,049; 95 % CI: 2.7-3.1 %) by excluding this study. The findings highlight the relatively high prevalence of C. cayetanensis infection in low-income countries and among humans with diarrhea, particularly in Africa. Consequently, routine surveillance for intestinal protozoa is crucial in these regions.
Subject(s)
Cyclospora , Cyclosporiasis , Humans , Africa/epidemiology , Cyclosporiasis/epidemiology , Cyclosporiasis/complications , Cyclosporiasis/parasitology , Diarrhea/parasitology , Feces/parasitology , PrevalenceABSTRACT
Blastocystis sp., Enterocytozoon bieneusi, and Giardia duodenalis are three common zoonotic intestinal parasites, and cattle are important hosts of these three intestinal protozoa. In this study, 1632 fecal samples were collected from dairy farms in Heilongjiang Province, China, and screened for Blastocystis sp., E. bieneusi, and G. duodenalis using polymerase chain reaction. Of these, 149 (9.13%) were positive for three zoonotic pathogens, including 104 (6.40%), 22 (1.35%), and 23 (1.41%) for Blastocystis sp., E. bieneusi, and G. duodenalis, respectively. Based on partial SSU rRNA gene sequencing analysis, 104 positive samples of Blastocystis sp. were found, and a total of nine known subtypes were identified, including ST10 (61), ST3 (18), ST14 (6), ST26 (7), ST24 (3), ST25 (2), ST1 (2), ST5 (2), and ST21 (1). Among these, three subtypes (ST1, ST3, and ST5) were recognized as zoonotic subtypes, and two subtypes (ST10 and ST14) were specific to animals. All 23 Giardia duodenalis-positive samples belonged to assemblage E (n = 23) based on sequenced beta-giardin (bg) and triosephosphate isomerase (tpi) genes. Three known genotypes of E. bieneusi, namely J (n = 9), I (n = 6), and BEB4 (n = 7), were identified by sequence analysis of the internal transcriptional spacer region gene. Our study provides basic data for prevention and control in Heilongjiang Province; however, further research is required to better understand the prevalence and public health significance of these pathogens in the Heilongjiang region.
Subject(s)
Cryptosporidium , Enterocytozoon , Giardia lamblia , Giardiasis , Microsporidiosis , Animals , Cattle , Giardia lamblia/genetics , Giardiasis/epidemiology , Giardiasis/veterinary , Giardiasis/parasitology , Enterocytozoon/genetics , Microsporidiosis/epidemiology , Microsporidiosis/veterinary , China/epidemiology , Genotype , Feces/parasitology , Prevalence , Cryptosporidium/geneticsABSTRACT
To investigate the prevalence and molecular characteristics of Cystoisospora sp. in blue fox (Alopex lagopus), Sheather's sugar floatation method was conducted to detect coccidia in 423 fresh fecal samples randomly collected from blue fox farms from three cities in China. The overall prevalence of coccidia was 1.4% (6/423), and three Cystoisospora sp. (Cystoisospora fennechi, Cystoisospora sp. I and Cystoisospora vulpina) were identified by their morphological characteristics. The 18S ribosomal RNA (rRNA) and cytochrome c oxidase subunit I (COI) locus sequences were sequenced for molecular biological identification, homology comparison, and phylogenetic analysis of Cystoisospora sp. by single-oocyst selection technology and multi-locus-nested PCR amplification. At the 18S rRNA and COI loci, C. vulpina had 99.48% and 99.59% homology, respectively, with Cystoisospora canis and Cystoisospora ohioensis from canines. Phylogenetic analysis indicated that C. vulpina was clustered in a clade with Cystoisospora sp. from Canidae, which the relatives are consistent with the hosts. To our knowledge, this is the first report on molecular identification and evolutionary analysis of C. vulpina at two different loci.
Subject(s)
Coccidia , Isospora , Sarcocystidae , Dogs , Animals , Foxes , Phylogeny , Sarcocystidae/genetics , Coccidia/genetics , Isospora/genetics , RNA, Ribosomal, 18S/geneticsABSTRACT
Giardia duodenalis is one of the major causes of diarrhea among humans, especially in young children. Statistical analysis revealed that the pooled prevalence of G. duodenalis in humans, dogs, and cats was 9.72% (10,921/112383), 15.60% (7510/48140), and 14.53% (1125/7740), respectively. Unquestionably, the canine-specific assemblages C and D and the feline-specific assemblage F were the dominant genotypes in dogs and cats, respectively. Additionally, the prevalence of zoonotic G. duodenalis assemblages (A and B) in dogs and cats was 23.07% (875/3792) and 41.42% (169/408), respectively, implying that the potential transmission of G. duodenalis from dogs and cats to human infection cannot be ignored. The highest frequency of potentially zoonotic assemblages was found among working dogs (3.55%, 25/705) and the 1-5 age group (22.92%, 11/48). In summary, dogs and cats have a significant role in the zoonotic transmission of G. duodenalis due to their close contact with humans and the higher frequency presence of zoonotic assemblages. Further studies are necessary to explore the presence of G. duodenalis among humans and animals and in environmental samples. Researchers should adopt a one-health approach to gain a deeper understanding of G. duodenalis in dogs and cats and potential transmission routes to humans.
ABSTRACT
BACKGROUND: With the promotion of "One Health," the health of animals and their impact on the environment have become major concerns recently. Widely distributed in China, the whooper swans (Cygnus cygnus) and black swans (Cygnus atratus) are not only important to the ecological environment, but they may also potentially influence public health security. The metagenomic approach was adopted to uncover the impacts of the gut microbiota of swans on host and public health. RESULTS: In this study, the intestinal microbiome and resistome of migratory whooper swans and captive-bred black swans were identified. The results revealed similar gut microbes and functional compositions in whooper and black swans. Interestingly, different bacteria and probiotics were enriched by overwintering whooper swans. We also found that Acinetobacter and Escherichia were significantly enriched in early wintering period swans and that clinically important pathogens were more abundant in black swans. Whooper swans and black swans are potential reservoirs of antibiotic resistance genes (ARGs) and novel ARGs, and the abundance of novel ARGs in whooper swans was significantly higher than that in black swans. Metagenomic assembly-based host tracking revealed that most ARG-carrying contigs originated from Proteobacteria (mainly Gammaproteobacteria). CONCLUSIONS: The results revealed spatiotemporal changes in microbiome and resistome in swans, providing a reference for safeguarding public health security and preventing animal epidemics.
Subject(s)
Anseriformes , Gastrointestinal Microbiome , Microbiota , One Health , Animals , Gastrointestinal Microbiome/genetics , China , Ducks , Anti-Bacterial Agents/pharmacologyABSTRACT
Coccidiosis caused by Eimeria is one of the most common diseases in domestic rabbits (Oryctolagus cuniculus f. domesticus), with 11 Eimeria species in domestic rabbits recognized internationally. To identify Eimeria species more accurately, a method based on the molecular characteristics of a single oocyst with multiple gene loci was established by combining morphological and molecular biology. The results showed that the total infection rate of Eimeria in domestic rabbits was 44.2 % (152/344). Ten Eimeria species were identified in domestic rabbits based on morphological characteristics, namely Eimeria vejdovskyi (39.5 %, 136/344), E. magna (18.0 %, 62/344), E. perforans (17.4 %, 60/344), E. intestinalis (12.5 %, 43/344), E. media (11.9 %, 41/344), E. coecicola (4.4 %, 15/344), E. irresidua (3.8 %, 13/344), E. exigua (2.6 %, 9/344), E. stiedai (2.3 %, 8/344), and E. piriformis (1.5 %, 5/344). The molecular biological identification of Eimeria in domestic rabbits was conducted through single oocyst selection and nested polymerase chain reaction amplification with multiple gene loci. We obtained the sequences of the 18S rRNA, ITS-1 and COI gene loci of E. magna, E. perforans, E. vejdovskyi, E. media, E. intestinalis, and E. coecicola. The results showed that the molecular biology and morphological identification results of single oocysts were consistent and could be used for the molecular identification of Eimeria at the single oocyst level. This study provides an efficient tool for identification of Eimeria in domestic rabbits and the population genetic study of Eimeria in domestic rabbits.
Subject(s)
Coccidiosis , Eimeria , Rabbits , Animals , Eimeria/genetics , Oocysts , Coccidiosis/veterinary , Coccidiosis/epidemiologyABSTRACT
Photocatalytic overall water splitting is a promising approach to overcome the environmental and energy crisis. However, developing effective photocatalysts with well activity, light absorption, and photogenerated carrier lifetime is still a challenge. Herein, combining extensive first-principles and nonadiabatic molecular dynamics calculations, we find that microporous carbon-nitride nanosheets with a pyridinic nitrogen, such as C2N and C6N6, possess the pentacoordinated silicon intermediates' bonding environment. The pentacoordinated silicon as intermediates exhibits good photocatalytic performance for the difficult four-electronic oxygen evolution reaction. The overpotential is only 0.55 V for C2N, which is significantly lower than that of the tetracoordinated silicon intermediates (2.00 V). Simultaneously, the decoration of the silicon group not only widens the absorption range of visible light but also maintains the lifetime of photogenerated carriers on the nanosecond scale, which enhances the application efficiency of solar energy. Our work paves a new route for advancing photocatalytic overall water splitting.
ABSTRACT
Blastocystis is a usual intestinal protist that always found in humans and various animals. Currently, the prevalence of Blastocystis in the migratory whooper swan (Cygnus cygnus) is unknown. In our research, we aimed to determine the occurrence, prevalence, subtype distribution and dynamic transmission mechanisms of Blastocystis in the migratory whooper swan in China. We also assessed the zoonotic potential of Blastocystis isolates, as well as possible routes of transmission and impact of this organism on One Health perspective. Fecal samples (n = 770) were collected from whooper swans inhabiting the Sanmenxia Swan Lake National Urban Wetland Park, China. The overall prevalence of Blastocystis was 11.6% (89/770). We identified 9 subtypes of Blastocystis sp., including 5 zoonotic subtypes [ST1 (Cakir et al., 2019 (8)), ST4 (Selma and Karanis, 2011 (4)), ST5 (Stensvold et al., 2009 (1)), ST6 (Fare et al., 2019 (5)) and ST7(58)] and 3 host-specific subtypes [ST10 (Zhao et al., 2018 (7)), ST14 (Tan et al., 2010 (2)), ST23 (Wang et al., 2018 (3)), and ST25 (Stensvold et al., 2009 (1))]. Subtypes ST4, ST5, ST6, ST10, ST14, ST23, and ST25 were first identified in the whooper swan. Among these subtypes, ST23 and ST25 were identified in birds for the first time, indicating that these subtypes are expanding their host range. So far, this is the first research reporting on the prevalence and subtypes distribution of Blastocystis in the migratory whooper swan in China. The findings obtained in this study will provide new insights into the genetic diversity and transmission routes of Blastocystis, and the possible public health concerns posed by this organism.
ABSTRACT
Cryptosporidium spp. are zoonotic intestinal parasites that infect fish, birds, reptiles and mammals. Cryptosporidium spp. are common cause of diarrhea. In this study, a total of 1032 fecal samples were collected from the rectums of sheep and goats. The samples were analyzed using nested polymerase chain reaction (nested PCR) based on the small subunit ribosomal RNA (SSU rRNA) gene of Cryptosporidium spp. The average infection rate of Cryptosporidium spp. was 2.23% (n = 23), and three Cryptosporidium species were identified, namely Cryptosporidium ubiquitum (8/23), Cryptosporidium andersoni (5/23) and Cryptosporidium xiaoi (10/23). Subtyping of C. ubiquitum and C. xiaoi was carried out by DNA sequence analysis of the 60-kDa glycoprotein (gp60) gene. Eight C. ubiquitum isolates were identified as zoonotic subtype XIIa. Nine C. xiaoi isolates were identified as subtypes XXIIIc (n = 1), XXIIIf (n = 3) and XXIIIg (n = 5). Subtype XXIIIg was first found in Chinese sheep. C. ubiquitum subtype XIIa was found in both sheep and goats, suggesting that sheep and goats are important sources of C. ubiquitum infections.
Subject(s)
Cryptosporidiosis , Cryptosporidium , Animals , Sheep , Cryptosporidiosis/epidemiology , Cryptosporidiosis/parasitology , Goats , Prevalence , China/epidemiology , Feces/parasitology , GenotypeABSTRACT
Nature harnesses exquisite enzymatic cascades to construct N-heterocycles and further uses these building blocks to assemble the molecules of life. Here we report an enzymatic platform to construct important chiral N-heterocyclic products, pyrrolidines and indolines, via abiological intramolecular C(sp3)-H amination of organic azides. Directed evolution of cytochrome P411 (a P450 enzyme with serine as the heme-ligating residue) yielded variant P411-PYS-5149, capable of catalyzing the insertion of alkyl nitrene into C(sp3)-H bonds to build pyrrolidine derivatives with good enantioselectivity and catalytic efficiency. Further evolution of activity on aryl azide substrates yielded variant P411-INS-5151 that catalyzes intramolecular C(sp3)-H amination to afford chiral indolines. In addition, we show that these enzymatic aminations can be coupled with a P411-based carbene transferase or a tryptophan synthase to generate an α-amino lactone or a noncanonical amino acid, respectively, underscoring the power of new-to-nature biocatalysis in complexity-building chemical synthesis.
ABSTRACT
This study i dentifies four Eimeria spp. recorded from fecal samples of migratory whooper swans (Cygnus cygnus) in Sanmenxia Swan Lake National Urban Wetland Park in Sanmenxia city in the middle reaches of the Yellow River, China. Eimeria hermani, Eimeria nocens, Eimeria stigmosa, and Eimeria magnalabia were compatible in all characteristic features with their respective original descriptions. In addition to the preliminary morphological identification, this study provides a preliminary genotypic identification of these four Eimeria spp. via sequencing of the 18S rRNA, 28S rRNA, and COI gene loci that are suitable for the genotypic differentiation of these coccidia. This is the first report of molecular data for the four Eimeria spp. in migratory whooper swans. Finally, this study discusses the environmental risks of these coccidia for migratory whooper swans in Sanmenxia Swan Lake National Urban Wetland Park.
Subject(s)
Anseriformes , Eimeria , Animals , China , Ducks , Eimeria/genetics , Lakes , Phylogeny , Rivers , WetlandsABSTRACT
Giardia duodenalis is an important zoonotic parasite that causes economic losses to animal husbandry and threatens public health. In the present study, a total of 1466 fresh fecal samples were collected from sheep (n = 797), goats (n = 561) and beef cattle (n = 108) in Southwest Inner Mongolia, China. Giardia duodenalis was initially screened via nested polymerase chain reaction (PCR) targeting the ß-giardin (bg) gene, and bg-positive samples were subjected to PCR amplification targeting the glutamate dehydrogenase (gdh) and triose phosphate isomerase (tpi) genes. A total of 4.0% of samples (58/1466) were positive for G. duodenalis, with a prevalence of 3.4% in sheep, 3.7% in goats and 5.2% in beef cattle. Three G. duodenalis assemblages (A, B, and E) were identified, with E as the prevalent assemblage. Four and one novel assemblage E sequences were obtained for the gdh and tpi loci, respectively and four assemblage E multilocus genotypes (MLG) were obtained. This study demonstrates high genetic variations in G. duodenalis assemblage E, and provides baseline data for preventing and controlling G. duodenalis infection in livestock in Inner Mongolia.
Title: Caractérisation moléculaire de Giardia duodenalis basée sur le génotypage multilocus chez les ovins, les caprins et les bovins dans le sud-ouest de la Mongolie intérieure, en Chine. Abstract: Giardia duodenalis est un parasite zoonotique important, qui cause des pertes économiques à l'élevage et menace la santé publique. Dans la présente étude, un total de 1466 échantillons fécaux frais ont été prélevés sur des moutons (n = 797), des chèvres (n = 561) et des bovins de boucherie (n = 108) dans le sud-ouest de la Mongolie intérieure, en Chine. Giardia duodenalis a été initialement criblé via une réaction en chaîne par polymérase imbriquée ciblant le gène de la ß-giardine (bg), et les échantillons bg-positifs ont été soumis à une amplification par PCR ciblant les gènes de la glutamate déshydrogénase (gdh) et de la triose phosphate isomérase (tpi). Au total, 4,0 % (58/1466) des échantillons étaient positifs pour G. duodenalis, avec une prévalence de 3,4 % chez les ovins, 3,7 % chez les caprins et 5,2 % chez les bovins. Trois assemblages de G. duodenalis (A, B et E) ont été identifiés, E étant l'assemblage prédominant. Respectivement quatre et une nouvelle séquences de l'assemblage E ont été obtenues dans les loci gdh et tpi, et quatre génotypes multilocus (MLG) de l'assemblage E ont été mis en évidence. Cette étude montre des variations génétiques élevées dans l'assemblage E de G. duodenalis et fournit des données de base pour prévenir et contrôler l'infection à G. duodenalis chez le bétail en Mongolie intérieure.
Subject(s)
Giardia lamblia , Giardiasis , Animals , Cattle , China/epidemiology , Feces/parasitology , Genotype , Giardia lamblia/genetics , Giardiasis/epidemiology , Giardiasis/parasitology , Giardiasis/veterinary , Glutamate Dehydrogenase/genetics , Goats/genetics , Multilocus Sequence Typing/veterinary , Protozoan Proteins/genetics , Sheep , Triose-Phosphate Isomerase/geneticsABSTRACT
The controlled isomerization and functionalization of alkenes is a cornerstone achievement in organometallic catalysis that is now widely used throughout industry. In particular, the addition of CO and H2 to an alkene, also known as the oxo-process, is used in the production of linear aldehydes from crude alkene feedstocks. In these catalytic reactions, isomerization is governed by thermodynamics, giving rise to functionalization at the most stable alkylmetal species. Despite the ubiquitous industrial applications of tandem alkene isomerization/functionalization reactions, selective functionalization at internal positions has remained largely unexplored. Here we report that the simple W(0) precatalyst W(CO)6 catalyses the isomerization of alkenes to unactivated internal positions and subsequent hydrocarbonylation with CO. The six- to seven-coordinate geometry changes that are characteristic of the W(0)/W(II) redox cycle and the conformationally flexible directing group are key factors in allowing isomerization to take place over multiple positions and stop at a defined unactivated internal site that is primed for in situ functionalization.
Subject(s)
Alkenes , Tungsten , Catalysis , Isomerism , Oxidation-ReductionABSTRACT
Propargyl amines are versatile synthetic intermediates with numerous applications in the pharmaceutical industry. An attractive strategy for efficient preparation of these compounds is nitrene propargylic C(sp3)-H insertion. However, achieving this reaction with good chemo-, regio-, and enantioselective control has proven to be challenging. Here, we report an enzymatic platform for the enantioselective propargylic amination of alkynes using a hydroxylamine derivative as the nitrene precursor. Cytochrome P450 variant PA-G8 catalyzing this transformation was identified after eight rounds of directed evolution. A variety of 1-aryl-2-alkyl alkynes are accepted by PA-G8, including those bearing heteroaromatic rings. This biocatalytic process is efficient and selective (up to 2610 total turnover number (TTN) and 96% ee) and can be performed on preparative scale.
Subject(s)
AlkynesABSTRACT
The direct reductive N-arylation of nitromethane by organophosphorus-catalyzed reductive C-N coupling with arylboronic acid derivatives is reported. This method operates by the action of a small ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) together with a mild terminal reductant hydrosilane to drive the selective installation of the methylamino group to (hetero)aromatic boronic acids and esters. This method also provides for a unified synthetic approach to isotopically labeled N-methylanilines from various stable isotopologues of nitromethane (i.e., CD3NO2, CH315NO2, and 13CH3NO2), revealing this easy-to-handle compound as a versatile precursor for the direct installation of the methylamino group.
Subject(s)
Amines/chemical synthesis , Boronic Acids/chemistry , Esters/chemistry , Methane/analogs & derivatives , Nitroparaffins/chemistry , Organophosphorus Compounds/chemistry , Amination , Amines/chemistry , Catalysis , Methane/chemistry , Molecular Structure , Oxidation-ReductionABSTRACT
The highly efficient copper-catalyzed enantioselective alkynylation of the remote C(sp3)-H bond on linear primary sulfonamides is presented here using a radical relay strategy. The chiral box-copper complex, which is used to recapture the in-situ-generated alkyl radical via a 1,5-HAT strategy, is the key to success, affording the chiral alkynes after a following reductive elimination. A general substrate scope, mild conditions, and excellent regio- and enantioselective control are demonstrated in this method.
ABSTRACT
NiO, Ni-Co-Mn-O x and NiO/Ni-Co-Mn-O x on nickel foam substrates were prepared via a chemical bath deposition-calcination. The thermodynamic behavior was observed by TG/DTA. The chemical structure and composition, phase structure and microstructures were tested by XPS, XRD, FE-SEM and TEM. The electrochemical performance was measured by CV, GCD and EIS. The mechanism for formation and enhancing electrochemical performance is also discussed. Firstly, the precursors such as NiOOH, CoOOH and MnOOH grow on nickel foam substrates from a homogeneous mixed solution via chemical bath deposition. Thereafter, these precursors are calcined and decomposed into NiO, Co3O4 and MnO2 respectively under different temperatures in a muffle furnace. Notably, NiO/Ni-Co-Mn-O x on nickel foam substrates reveals a high specific capacity with 1023.50 C g-1 at 1 A g-1 and an excellent capacitance retention with 103.94% at 5 A g-1 after 3000 cycles in 2 M KOH, its outstanding electrochemical performance and cycling stability are mainly attributed to a porous sheet-sheet hierarchical nanostructure and synergistic effects of pseudo-capacitive materials and excellent redox reversibility. Therefore, this research offers a facile synthesis route to transition metal oxides for high performance supercapacitors.
ABSTRACT
The direct functionalization of C(sp3)-H bonds has led to the development of methods to access molecules or intermediates from basic chemicals in an atom- and step-economic fashion. Nevertheless, achieving high levels of chemo-, regio-, and enantioselectivity in these reactions remains challenging due to the ubiquity and low reactivity of C(sp3)-H bonds. Herein, we report an unprecedented protocol for enantioselective cyanation of remote C(sp3)-H bonds. With chiral Box-Cu complex as the catalyst, the reaction of N-fluorosulfonamide furnishes the corresponding products in excellent yields and high enantiomeric excess (ee) under mild reaction conditions. A radical relay pathway involving 1,5-hydrogen atom transfer (1,5-HAT) of N-center radicals followed by enantioselective cyanation of the in situ-formed benzyl radicals is proposed. This enantioselective copper-catalyzed cyanation thus offers insights into an efficient way for the synthesis of bioactive molecules for drug discovery.
ABSTRACT
This manuscript describes a modular method for preparing N-alkyl phosphinic amides from primary or secondary alcohols and primary phosphinic amide (R1R2P=ONH2) nucleophiles via transfer hydrogenation. The transformation typically proceeds in excellent yields, employs conveniently available reagents, and produces water as the only byproduct.