Amino Aldehydes Research Articles

A modified Mediterranean‐ketogenic diet favorably modulates the metabolic profiles of mild cognitively impaired individuals

AbstractBackgroundImpaired glucose utilization is central to the pathogenesis of Alzheimer’s disease. In a hypometabolic state, the brain depends on alternative sources of energy, including amino acids, fatty acids, and ketone bodies (KBs). As KBs can cross the blood‐brain barrier, it is considered that a ketogenic diet could augment the high energetic demand of the central nervous system (CNS). A ketogenic diet is already a part of clinical care in epilepsy a CNS disorder. However, the holistic benefits of this diet for Alzheimer’s remain to be determined.MethodsA randomized crossover pilot trial was conducted where participants consumed either the Modified Mediterranean‐Ketogenic Diet (MMKD) or the American Heart Association Diet (AHAD) for 6 weeks, followed by a 6‐week washout, after which the respective other diet was consumed for 6 weeks. The cohort included both mild cognitively impaired (MCI) and cognitively normal (CN) individuals. Serum and cerebrospinal fluid (CSF) samples of these individuals were profiled using two metabolic platforms: MS‐based and NMR‐based metabolomics. Diet‐related changes in levels of metabolites were determined using linear‐mixed effect models with age and sex as confounders.ResultsWe identified post‐diet changes in the two diet groups (AHAD and MMKD), two cognitive groups (MCI and CN), and two fluids (serum and CSF). AHAD was associated with a decrease in serum levels of only a single metabolite, glutamine. MMKD led to widespread lipidomic and metabolic changes in the serum of mild cognitively impaired individuals. Remarkably, MMKD was associated with the reversal of AD‐related metabolic alterations identified in large cohorts like ADNI, AIBL, ROS/MAP, and signature for incident dementia in large epidemiological studies. The post‐MMKD changes include correcting metabolic dysregulation in branched‐chain amino acids, triglycerides, and plasmalogens a class of lipids implicated in membrane structure and function. Peripheral‐central metabolic correlations will be shared.ConclusionOur findings highlight the potential of dietary interventions, specifically the MMKD, in improving the cognitive and metabolic state of individuals with MCI. Further investigation is needed to capture the entirety of MMKD‐related modulation in metabolic profiles and the resulting benefit for AD.

Abstract 13276: Metabolic Pathways and Risk Biomarkers for Incident Heart Failure

Introduction: Metabolomic profiling provides important information about heart failure (HF) risk. Metabolites reporting on muscle fuel substrate including branched-chain amino acids (BCAAs) and ketones have been implicated in HF pathogenesis and as circulating biomarkers of risk. We sought to identify the role of these known metabolites and identify novel metabolites and related pathways associated with incident HF in a large population-based cohort. Methods: Metabolomic profiling has been performed in the UK Biobank cohort using the Nightingale NMR platform. Principal component analysis (PCA) was used for dimensionality reduction and to identify shared metabolic pathways. Cox proportional hazard models were used to test the association between each PCA factor, and of individual metabolites heavily loaded on significant factors, with time to incident HF. Results: Of n=118,021 participants with metabolomic profiling data, n=3,865 (3.3%) developed incident HF (mean [SD] follow-up: 12.5 [1.3] years). The 107 metabolite biomarkers clustered into 12 PCA factors (Table 1). Nine factors were associated with incident HF in adjusted models. Factor 5 (BCAAs, aromatic acids) was not associated with incident HF in adjusted models. However, higher levels of each individual BCAA were associated with decreased risk of incident HF, with valine as the most protective (HR 0.91 [CI 0.88-0.95], q = 3x10 -6 ). Factors 2 (large HDL) and 6 (ketones) were associated with increased risk of incident HF, while factors 4 (small HDL) and 9 (omega-3 fatty acids) were associated with decreased risk of incident HF. Conclusions: In a large population-based cohort, we found that higher baseline levels of ketones and large HDL were associated with increased risk of incident HF, while higher levels of BCAAs, small HDL, and omega-3 fatty acids were associated with decreased risk of incident HF. These results highlight known and new metabolic pathways and related circulating biomarkers of HF risk.

Cross-sectional Association Between Plasma Biomarkers and Multimorbidity Patterns in Older Adults.

Multimorbidity is the simultaneous presence of 2 or more chronic conditions. Metabolomics could identify biomarkers potentially related to multimorbidity. We aimed to identify groups of biomarkers and their association with different multimorbidity patterns. Cross-sectional analyses were conducted within the Seniors-ENRICA-2 cohort in Spain, with information from 700 individuals aged ≥65 years. Biological samples were analyzed using high-throughput proton nuclear magnetic resonance metabolomics. Biomarker groups were identified with exploratory factor analysis, and multimorbidity was classified into 3 types: cardiometabolic, neuropsychiatric, and musculoskeletal. Logistic regression was used to estimate the association between biomarker groups and multimorbidity patterns, after adjusting for potential confounders including sociodemographics, lifestyle, and body mass index. Three factors were identified: the "lipid metabolism" mainly reflected biomarkers related to lipid metabolism, such as very-low-density lipoprotein and low-density lipoprotein cholesterol; the "high-density lipoprotein cholesterol" mainly included high-density lipoprotein cholesterol subclasses and other lipids not included in the first factor; and the "amino acid/glycolysis/ketogenesis," composed of some amino acids, glycolysis-related metabolites, and ketone bodies. Higher scores in the "lipid metabolism" factor were associated with a higher likelihood of cardiometabolic multimorbidity, odds ratio for tertile 3 versus tertile 1 was 1.79 (95% confidence interval: 1.17-2.76). The "high-density lipoprotein cholesterol" factor was associated with lower odds of cardiometabolic multimorbidity [0.51 (0.32-0.82)], and the "amino acid/glycolysis/ketogenesis" factor was associated with more frequent cardiometabolic multimorbidity [1.85 (1.18-2.90)]. Different metabolomic biomarkers are associated with different multimorbidity patterns; therefore, multiple biomarker measurements are needed for a complete picture of the molecular mechanisms of multimorbidity.

Cobalt-Catalyzed Efficient Asymmetric Hydrogenation of α-Primary Amino Ketones.

Based on an amino-group-assisted coordination strategy and a proton-shuttle-activated outer-sphere mode, the cobalt-catalyzed asymmetric hydrogenation of α-primary amino ketones has been developed, resulting in the efficient synthesis of chiral vicinal amino alcohols bearing functionalized aryl rings in high yields and enantioselectivities (up to 99% enantiomeric excess (ee)) within 0.5 h.

Comprehensive quantification of metabolic flux during acute cold stress in mice

Cold-induced thermogenesis (CIT) is widely studied as a potential avenue to treat obesity, but a thorough understanding of the metabolic changes driving CIT is lacking. Here, we present a comprehensive and quantitative analysis of the metabolic response to acute cold exposure, leveraging metabolomic profiling and minimally perturbative isotope tracing studies in unanesthetized mice. During cold exposure, brown adipose tissue (BAT) primarily fueled the tricarboxylic acid (TCA) cycle with fat in fasted mice and glucose in fed mice, underscoring BAT's metabolic flexibility. BAT minimally used branched-chain amino acids or ketones, which were instead avidly consumed by muscle during cold exposure. Surprisingly, isotopic labeling analyses revealed that BAT uses glucose largely for TCA anaplerosis via pyruvate carboxylation. Finally, we find that cold-induced hepatic gluconeogenesis is critical for CIT during fasting, demonstrating a key functional role for glucose metabolism. Together, these findings provide a detailed map of the metabolic rewiring driving acute CIT.

Comparison of the effects of pea protein and whey protein on the metabolic profile of soccer athletes: a randomized, double-blind, crossover trial.

Pea protein (PP) concentrate is a plant-based alternative to animal protein sources, such as whey protein (WP). In addition to its valuable amino acid composition, PP has a low environmental impact, making it a sustainable, nutritious, and viable alternative for enhanced sports performance, such as in soccer. PP Therefore, this study aimed to evaluate the effects of PP and WP supplementation on biochemical and metabolic parameters in soccer players. Twelve male under-20 soccer players were included in this double-blind, randomized crossover intervention study. For 10 consecutive days, each participant received either 0.5 g/kg of the PP or WP supplementation after training, starting 7 days before the test game, and continuing until 2 days after. After a 4-day washout period, the athletes switched groups and the intervention was restarted. Blood samples were collected before and after the game, as well as 24 h, 48 h, and 72 h intervals thereafter. Creatine kinase (CK), aspartate transaminase, alanine transaminase (ALT), lactate (LA), urea, creatinine, and uric acid were analyzed using commercial kits. Exploratory metabolic profiling of the serum samples was performed using nuclear magnetic resonance spectroscopy. A comparison of biochemical markers showed that the PP group had lower CK in the post-game moment, 24 h, and 48 h. Lower LA in the post-game moment, and lower ALT in the post-game moment and at 24 h. Of the 48 metabolites analyzed, 22 showed significant differences between the time points, such as amino acids, ketone bodies, and glucose metabolism. Glutamate and lactate levels significantly increased between the pre- and post-game moments in the WP group. After the game, the WP group exhibited reduced levels of metabolites such as arginine and taurine, whereas no such change was observed in the PP group. There was no difference in metabolites 72 h after the game. Despite the slight advantage of the PP group in specific biochemical markers, these differences are not sufficient to justify the choice of a particular type of protein. However, the results highlight the viability of plant protein as a potential alternative to animal protein without compromising athletic performance or recovery.

Design and synthesis of novel 1,3-diene bridged chiral atropoisomeric diphosphine ligands for asymmetric hydrogenation of α-dehydro amino ketones

Design and synthesis of novel 1,3-diene bridged chiral atropoisomeric diphosphine ligands for asymmetric hydrogenation of α-dehydro amino ketones

Changes in volatile and nutrient components of mango juice by different Lactic acid bacteria fermentation

This study investigated the changes in volatile and nutrient compounds of mango juice fermentation by lactic acid bacteria (LAB) (Lactobacillus plantarum NCU116, Lactobacillus acidophilus NCU402, and Lactobacillus casei NCU215). All strains grew well and L. plantarum NCU116 yielded the highest acidity and lactic acid content during fermentation. Meanwhile, L. plantarum NCU116 and L. acidophilus NCU402 fermentation significantly decreased L* and a* values. L. acidophilus NCU402 fermented mango showed the lowest levels of nitrite (0.01 μmol/g) and carotenoids (44.98 μg/g). Additionally, LAB fermentation enhanced aroma of mango juice by elevating alcoholic compounds and reducing terpenoids and aldehydes, with L. plantarum NCU116 demonstrating the most notable impact, increasing alcohol concentration from 5% to 17%. Correlation analysis revealed that key alcohols production was associated with amino acids, sugar, aldehydes, and terpenoids. According to the sensory analysis, the mango juice inoculated with L. casei NCU215 had the highest acceptability score. Thus, the type of LAB strains determined the nutrient component, volatile and sensory profile of mango juices and further research is needed to understand the fermentation mechanisms.

Chemometrics-based investigation of non-volatiles/volatiles flavor of tencha (Camellia sinensis cv. Yabukita, Longjing 43 and Baiye 1)

The increasing demand for tea consumption calls for the development of more products with distinct characteristics. The sensory quality of tencha is significantly determined by innate differences among tea cultivars. However, the correlations between the chemical composition and sensory traits of tencha are still unclear. To enhance the understanding of the flavor formation mechanism in tencha and further to develop new cultivars resources, we investigated non-volatiles and volatile metabolites as well as sensory traits in tencha from different tea cultivars (Camellia sinensis cv. Yabukita, Longjing 43 and Baiye 1); the relationships between the flavor traits and non-volatiles/volatiles were further evaluated by partial least squares - discriminate analysis (PLS-DA), multiple factor analysis (MFA) and multidimensional alignment (MDA) analysis. A total of 64 non-volatiles and 116 volatiles were detected in all samples, among which 71 metabolites were identified as key flavor-chemical contributors involving amino acids, flavonol glycosides, flavones, catechins, ketones, alcohols, hydrocarbons, aldehydes, esters and acids. The levels of taste-related amino acids, flavonol glycosides and gallic acid varied significantly among the tencha samples made from different tea cultivars. All the samples exhibited typical quality characteristics of tencha. The tencha from Camellia sinensis cv. Longjing 43 and Camellia sinensis cv. Baiye 1 (cultivated in the open) exhibited higher levels of amino acids and gallic acid, which were associated with the umami taste and mellow taste of tea infusion. Abundant flavonol glycosides were related to the astringency, while partial tri-glycosides specifically quercetin-3-O-galactoside-rhamnoside-glucoside and total of flavonol galactoside-rhamnoside-glucoside were associated with mellow taste. The floral alcohols were identified as significant contributors to the refreshing aroma traits of tencha. The green, almond-like, acidic and fruity odorants were associated with a green and fresh aroma, while the green, cheesy and waxy odorants such as ketones, esters, acids and hydrocarbons were associated with seaweed-like aroma. This study provides insight into sensory-related chemical profiles of tencha from different tea cultivars, supplying valuable information on flavor and quality identification for tencha.

Identifying a New Target for BtOBP8: Discovery of a Small Amino Ketone Molecule Containing Benzothiazole Fragments.

Insects rely on odorant-binding proteins (OBPs) for chemical perception, making OBPs a promising target for studying attractants and repellents of pests, such as Bemisia tabaci. However, no reports have reported using B. tabaci OBPs (BtOBPs) as pesticide screening targets. To fill this gap, we obtained BtOBP8 through prokaryotic expression and purification. Then, we confirmed its identity using western blotting and mass spectrometry. Next, we used the sitting drop and hanging drop methods to screen its crystal conditions. Using microscale thermophoresis and isothermal titration calorimetry, we identified the highest affinity ligand, 3l, from 30 compounds. Furthermore, point mutation techniques identified Val119 as a key amino acid residue in binding 31 to BtOBP8. Finally, we tested the bioactivity of B. tabaci Mediterranean and found that 3l more effectively inhibits the bioactivity of B. tabaci MED than imidacloprid. This study presents a new approach for developing green insecticides specific to B. tabaci MED by targeting OBPs. Conclusively, identifying and targeting specific OBPs can create more targeted and effective pest control strategies without relying on toxic chemicals.

Characterisation of Fasting and Postprandial NMR Metabolites: Insights from the ZOE PREDICT 1 Study.

Postprandial metabolomic profiles and their inter-individual variability are not well characterised. Here, we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability, following a standardised meal in the ZOE PREDICT 1 cohort. In the ZOE PREDICT 1 study (n = 1002 (NCT03479866)), 250 metabolites, mainly lipids, were measured by a Nightingale NMR panel in fasting and postprandial (4 and 6 h after a 3.7 MJ mixed nutrient meal, with a second 2.2 MJ mixed nutrient meal at 4 h) serum samples. For each metabolite, inter- and intra-individual variability over time was evaluated using linear mixed modelling and intraclass correlation coefficients (ICC) were calculated. Postprandially, 85% (of 250 metabolites) significantly changed from fasting at 6 h (47% increased, 53% decreased; Kruskal-Wallis), with 37 measures increasing by >25% and 14 increasing by >50%. The largest changes were observed in very large lipoprotein particles and ketone bodies. Seventy-one percent of circulating metabolites were strongly correlated (Spearman's rho >0.80) between fasting and postprandial timepoints, and 5% were weakly correlated (rho <0.50). The median ICC of the 250 metabolites was 0.91 (range 0.08-0.99). The lowest ICCs (ICC <0.40, 4% of measures) were found for glucose, pyruvate, ketone bodies (β-hydroxybutyrate, acetoacetate, acetate) and lactate. In this large-scale postprandial metabolomic study, circulating metabolites were highly variable between individuals following sequential mixed meals. Findings suggest that a meal challenge may yield postprandial responses divergent from fasting measures, specifically for glycolysis, essential amino acid, ketone body and lipoprotein size metabolites.

Dynamics of bacterial community, metabolites profile and physicochemical characteristics during solid-state fermentation of soybean meal and corn mixed substrates inoculated with Bacillus pumilus and Limosilactobacillus fermentum.

Solid-state fermentation (SSF) is a general approach for preparing food and feed, which not only improves nutrition but also provides prebiotics and metabolites. Although many studies have been conducted on the effects of fermentation on feed substrate, the dynamics of microbiota and metabolites in SSF remain unclear. Here, high-throughput sequencing combined with gas chromatography-quadrupole time-of-flight mass spectrometry was used to evaluate the dynamic changes of solid fermented soybean meal and corn mixed matrix inoculated with Bacillus pumilus and Limosilactobacillus fermentum. Generally, inoculated bacteria rapidly proliferated, accompanied by the degradation of macromolecular proteins and an increase in the content of small peptides, trichloroacetic acid-soluble protein, free amino acids and organic acids. Bacillus, Lactobacillus and Enterococcus dominated the whole fermentation process. 389 non-volatile metabolites and 182 volatile metabolites were identified, including amino acids, organic acids, ketones, aldehydes, furans and pyrazine. Typical non-volatile metabolites such as lactic acid, 4-aminobutanoic acid, l-glutamic acid, d-arabinose and volatile metabolites such as 4-ethyl-2-methoxyphenol, 4-penten-2-ol, 2-pentanone, 2-ethylfuran, 2-methylhexanoic acid and butanoic acid-ethyl ester were significantly increased in two-stage solid fermentation. However, some adverse metabolites were also produced, such as oxalic acid, acetic acid, tyramine and n-butylamine, which may affect the quality of fermented feed. Sixteen genera were significantly correlated with differential non-volatile metabolites, while 11 genera were significantly correlated with differential volatile metabolites. These results characterized the dynamic changes in the process of two-stage solid-state fermentation with Bacillus pumilus and Limosilactobacillus fermentum and provided a potential reference for additional intervention on improving the effectiveness and efficiency of solid-state fermentation of feed in the future. © 2023 Society of Chemical Industry.

Synthesis of Chiral α‐Amino Ketones via Transition Metal Catalyzed or Photoredox Cross‐Coupling and Olefin Photo‐Cleavage Reaction Sequence

AbstractWe report a convenient two‐step approach to α‐amino ketones involving cross‐coupling and oxidative cleavage sequence. The cross‐coupling reaction creates a divergent functionalization of the molecular platform, e. g., N‐(2‐bromoallyl)amine, whereas the oxidative cleavage establishes the carbonyl functionality. This strategy allows for an introduction of aryl/heteroaryl and alkyl groups, either through the Suzuki reaction with arylboronic acids or via dual photoredox/Ni‐catalysis to install alkyl groups. The oxidative cleavage to provide target α‐amino ketones can be realized either by treating with ozone or by employing milder photochemical protocols involving oxygen or photoexcited nitroarenes as oxidants. We successfully demonstrate the scalability of this protocol, which, together with its simplicity, generality, and its ability to provide access to amino ketones that are inaccessible through other strategies, highlights the suitability of this approach for a wide range of applications across the different chemical sciences.magnified image

Regioselective Cyclic Iminium Formation of Ugi Advanced Intermediates: Rapid Access to 3,4-Dihydropyrazin-2(1H)-ones and Other Diverse Nitrogen-Containing Heterocycles

Herein, advanced intermediates were synthesized through Ugi four-component reactions of isocyanides, aldehydes, masked amino aldehyde, and carboxylic acids, including N-protected amino acids. The presence of a masked aldehyde enabled acid-mediated deprotection and subsequent cyclization via the carbonyl carbon and the amide nitrogen. Utilizing N-protected amino acid as a carboxylic acid component, Ugi intermediates could be cyclized from two possible directions to target 3,4-dihydropyrazin-2(1H)-ones. Cyclization to the amino terminus (westbound) and to the carboxyl terminus (eastbound) was demonstrated. Deliberate selection of building blocks drove the reaction regioselectively and yielded diverse heterocycles containing a 3,4-dihydropyrazin-2(1H)-one core, pyrazin-2(1H)-one, and piperazin-2-one, as well as a tricyclic framework with a 3D architecture, 2,3-dihydro-2,6-methanobenzo[h][1,3,6]triazonine-4,7(1H,5H)-dione, from Ugi adducts under mild reaction conditions. The latter bridged heterocycle was achieved diastereoselectively. The reported chemistry represents diversity-oriented synthesis. One common Ugi advanced intermediate was, without isolation, rapidly transformed into various nitrogen-containing heterocycles.

Reducing dielectric confinement effect in ionic covalent organic nanosheets to promote the visible-light-driven hydrogen evolution

Ultra-thin two-dimensional (2D) organic semiconductors are promising candidates for photocatalysts because of the short charge diffusion pathway and favorable exposure of active sites plus the versatile architecture. Nonetheless, the inherent dielectric confinement of 2D materials will induce a strong exciton effect hampering the charge separation. Herein, we demonstrated an effective way to reduce the dielectric confinement effect of 2D ionic covalent organic nanosheets (iCONs) by tailoring the functional group via molecular engineering. Three ultra-thin CONs with different functional groups and the same ionic moieties were synthesized through Schiff base condensation between ionic amino monomer triaminoguanidinium chloride (TG) and aldehyde linkers. The integration of the hydroxyl group was found to significantly increase the dielectric constant by enhancing the polarizability of ionic moieties, and thus reduced the dielectric confinement and the corresponding exciton binding energy (Eb). The champion hydroxyl-functional iCON exhibited promoted exciton dissociation and in turn a high photocatalytic hydrogen production rate under visible-light irradiation. This work provided insights into the rationalization of the dielectric confinement effect of low-dimensional photocatalysts.

A Comprehensive Investigation of the Potential Role of Lipoproteins and Metabolite Profile as Biomarkers of Alzheimer's Disease Compared to the Known CSF Biomarkers.

While cerebrospinal fluid (CSF) core biomarkers have been considered diagnostic biomarkers for a long time, special attention has been recently dedicated to lipoproteins and metabolites that could be potentially associated with Alzheimer's disease (AD) neurodegeneration. Herein, we aimed to investigate the relationship between the levels of CSF core biomarkers including Aβ-42, TAU, and P-TAU and plasma lipoproteins and metabolites of patients with AD from the baseline cohort of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Using the ADNI database, fourteen subclasses of lipoproteins as well as a number of lipids and fatty acids and low-molecular metabolites including amino acids, ketone bodies, and glycolysis-related metabolites in blood samples were measured as potential noninvasive markers, and their association with the CSF core biomarkers was statistically investigated controlling for age and gender. A total number of 251 AD subjects were included, among whom 71 subjects were negative for the Apo-E ε4 allele and 150 were positive. There was no significant difference between the two groups regarding cognitive assessments, CSF core biomarkers, and lipoproteins and metabolites except the level of Aβ-42 (p < 0.001) and phenylalanine (p = 0.049), which were higher in the negative group. CSF TAU and P-TAU were significantly correlated with medium and small HDL in the negative group, and with extremely large VLDL in the positive group. Our results also indicated significant correlations of metabolites including unsaturated fatty acids, glycerol, and leucine with CSF core biomarkers. Based on our findings, a number of lipoproteins and metabolites were associated with CSF core biomarkers of AD. These correlations showed some differences in Apo-E ε4 positive and negative groups, which reminds the role of Apo-E gene status in the pathophysiology of AD development. However, further research is warranted to explore the exact association of lipoproteins and other metabolites with AD core biomarkers and pathology.

Charges and Volumes of Functional Groups of Amino Acids and Amino Aldehydes

Charges and Volumes of Functional Groups of Amino Acids and Amino Aldehydes

Dietary advanced glycation end products (dAGEs): An insight between modern diet and health

Advanced glycation end products (AGEs) are formed by a series of chemical reactions of amino acids, peptides, proteins, and ketones at normal temperature or heated non-enzymatic conditions. A large amount of AGEs derived from Maillard Reaction (MR) during the process of food heat-processing. After oral intake, dietary AGEs are converted into biological AGEs through digestion and absorption, and accumulated in almost all organs. The safety and health risk of dietary AGEs have attracted wide attention. Increasing evidence have shown that uptake of dietary AGEs is closely related to the occurrence of many chronic diseases, such as diabetes, chronic kidney disease, osteoporosis, and Alzheimer’s disease. This review summarized the most updated information of production, bio-transport in vivo, detection technologies, and physiological toxicity of dietary AGEs, and also discussed approaches to inhibit dietary AGEs generation. Impressively, the future opportunities and challenges on the detection, toxicity, and inhibition of dietary AGEs are raised.

Diastereoselective Synthesis of trans-β-Amino Cyclohexyl Ketones and trans-3-Amino-4-acyl-tetrahydropyrans from Intramolecular C-Alkylation of ω-Halo-Substituted β-Sulfinamido Ketones.

Reaction of ω-halo-substituted nonracemic β-sulfinamido ketones with NaH afforded the β-amino cyclohexyl ketones in excellent yields and diastereoselectivity, via an intramolecular C-alkylation, α to the carbonyl group. The reaction was found to be general and can be applied for the synthesis of different cyclohexyl amino ketones and tetrahydropyrans possessing amine and acyl substitutions.

Atlas of plasma NMR biomarkers for health and disease in 118,461 individuals from the UK Biobank

Blood lipids and metabolites are markers of current health and future disease risk. Here, we describe plasma nuclear magnetic resonance (NMR) biomarker data for 118,461 participants in the UK Biobank. The biomarkers cover 249 measures of lipoprotein lipids, fatty acids, and small molecules such as amino acids, ketones, and glycolysis metabolites. We provide an atlas of associations of these biomarkers to prevalence, incidence, and mortality of over 700 common diseases (nightingalehealth.com/atlas). The results reveal a plethora of biomarker associations, including susceptibility to infectious diseases and risk of various cancers, joint disorders, and mental health outcomes, indicating that abundant circulating lipids and metabolites are risk markers beyond cardiometabolic diseases. Clustering analyses indicate similar biomarker association patterns across different disease types, suggesting latent systemic connectivity in the susceptibility to a diverse set of diseases. This work highlights the value of NMR based metabolic biomarker profiling in large biobanks for public health research and translation.