A novel free C-12 higher carbon sugar: asymmetric synthesis and reactivity with nucleophiles

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComputer-assisted synthetic analysis. The identification and protection of interfering functionality in machine-generated synthetic intermediatesE. J. Corey, H. W. Orf, and David A. PensakCite this: J. Am. Chem. Soc. 1976, 98, 1, 210–221Publication Date (Print):January 1, 1976Publication History Published online1 May 2002Published inissue 1 January 1976https://pubs.acs.org/doi/10.1021/ja00417a032https://doi.org/10.1021/ja00417a032research-articleACS PublicationsRequest reuse permissionsArticle Views129Altmetric-Citations16LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

ChemInform Abstract: COMPUTER‐ASSISTED SYNTHETIC ANALYSIS. THE IDENTIFICATION AND PROTECTION OF INTERFERING FUNCTIONALITY IN MACHINE‐GENERATED SYNTHETIC INTERMEDIATES

Sugarcane, with its exceptional carbon dioxide assimilation, biomass and sugar yield, has a high potential for the production of bio-energy, bio-plastics and high-value products in the food and pharmaceutical industries. A crucial challenge for long-term economic viability and environmental sustainability is also to optimize the production of biomass composition and carbon sequestration. Sugarcane varieties such as KQ228 and Q253 are highly utilized in the industry. These varieties are characterized by a high early-season sugar content associated with high yield. In order to investigate these correlations, 1,440 internodes were collected and combined to generate a set of 120 samples in triplicate across 24 sugarcane cultivars at five different development stages. Weighted gene co-expression network analysis (WGCNA) was used and revealed for the first time two sets of co-expressed genes with a distinct and opposite correlation between fibre and sugar content. Gene identification and metabolism pathways analysis was used to define these two sets of genes. Correlation analysis identified a large number of interconnected metabolic pathways linked to sugar content and fibre content. Unsupervised hierarchical clustering of gene expression revealed a stronger level of segregation associated with the genotypes than the stage of development, suggesting a dominant genetic influence on biomass composition and facilitating breeding selection. Characterization of these two groups of co-expressed key genes can help to improve breeding program for high fibre, high sugar species or plant synthetic biology.

A simple, one‐pot multi‐step route for the synthesis of a higher carbon sugar 3 by the HDA reaction of a α,β‐unsaturated ketone prepared in situ from protected D‐xylose with PDC in C6H6 or CH3CN, followed by the reduction to the C10 higher carbon sugar derivatives 4 and 5, is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Reversed C-acyl glycosides represent a versatile class of nonclassical glycosides with potential in complex carbohydrate synthesis, including l-sugars, higher-carbon sugars, and medicinal chemistry. Conventional strategies for l- and higher-carbon sugars are limited by multi-step protection–deprotection sequences and poor stereocontrol. Herein, we report a general Pd-catalyzed reversed acyl C-glycosylation that efficiently couples configurationally stable reversed glycosyl stannanes with C(sp2)- and C(sp3)-derived thioesters under mild conditions. The reaction proceeds with complete stereoretentive transfer, enabling precise access to both d- and l-type glycosides, including higher-carbon sugar derivatives and C-ferrocenecarbonyl glycosides. The broad substrate scope, excellent functional group tolerance, and predictable stereochemical outcome highlight the robustness and synthetic versatility of this approach. Applications of the resulting reversed C-acyl glycosides as chiral synthons enable d-to-l interconversion, construction of l-sugar analogues, and derivatization toward designer carbohydrate frameworks. Importantly, this transformation enables a distinct d-to-l conversion featuring simultaneous C4 and C5 inversion, unlike conventional methods that modify only C5 configuration. Overall, this protocol establishes a general platform for stereocontrolled construction and diversification of structurally defined nonclassical glycosides, providing a foundation for glycodiversification, complex sugar synthesis, and exploration of biologically relevant C-glycosyl scaffolds.

The monosaccharide derivatives containing the C-Sn and C-Li bonds are reviewed. Both types of these organometallics are useful intermediates in the synthesis of variety of optically pure compounds such as higher carbon sugars, C-disaccharides, carbocyclic derivatives, etc. Organometallics containing the C-Sn bond are usually stable and can be isolated in the pure form, but their reactivity is low. The tin moiety in such compounds can be replaced by the lithium atom, leading to derivatives with the C-Li bond. The latter are highly reactive but unstable. However, the lithium atom in such unstable organometallics can be replaced with tin moiety, thus providing stable stannyl intermediates, which can be easily purified. Such a facile mutual exchangeability of the metal (Li→ ;Sn and vice versa) makes these sugar organometallics particularly attractive during stereocontrolled syntheses. In this review carbohydrate derivatives containing the metal atom (tin or lithium) placed at the sp³ carbon atom as well as at sp² and sp centers (at various positions of the sugar molecule) are reviewed. In addition, selected derivatives in which the metal is connected directly to the anomeric center are described. General methods of the synthesis of these important organometallic intermediates are evaluated. Application of lithiated or stannylated monosaccharide derivatives in the stereoselective syntheses is emphasized. The mechanistic aspects of these processes are discussed. Keywords: carbohydrate derivatrive, carbon-lithium bond, carbon-tin bond, c-sn bond, c-li bond, carbon-sugars, carbocyclic derivative

Methodology of the synthesis of higher carbon sugars containing > 10 carbon atoms in the chain is reviewed. The emphasis is put on such derivatives which can be (or are) easily converted into higher alditols. Keywords: Higher carbon sugars, higher alditols, stereoselective synthesis, natural products.

Production of rare sugars by transketolase in combination with ketose 3-epimerase.

Breast cancer ranks as the second leading cause of cancer-related mortality among women. The importance of lifestyle factors in cancer prevention is gaining momentum. Advanced Glycation End-products (AGEs) are reactive metabolites formed as a result of a spontaneous non-enzymatic reaction between reactive carbonyl and amine groups, they are irreversible and they accumulate in our bodies as we grow older. Dietary habits including high fat, high sugar and ultra-processed foods, contribute to the increased consumption of AGEs, and our collaborative group have linked the increased consumption of AGEs to the increased incidence of breast cancer and worse outcomes associated with the disease. Unfortunately, the mechanisms linking AGE consumption and breast cancer progression remain inadequately understood. AGEs can bind to and activate the Receptor for AGE (RAGE), prompting inflammatory responses and oxidative stress, potentially contributing to cancer development. We have developed a unique dietary-AGE mouse model to mimic human AGE consumption. In recently published studies, we found that mice fed a high AGE diet during puberty had dysregulation of normal mammary gland development. We also found hyperproliferative lesions in the high AGE fed mice with increased stromal recruitment including fibroblasts and macrophages. Primary fibroblasts isolated from the mouse mammary glands displayed an activated phenotype, similar to that observed in cancer associated fibroblasts, and led to increased epithelial cell migration and invasion in co-culture assays when compared to fibroblasts isolated from regular fed mice. We were able to recapitulate this phenotype with exogenous AGE treatment ex vivo, and found that the AGE-mediated effect on migration was dependent on RAGE expression in fibroblasts. In new unpublished studies, we found that dietary AGE consumption promotes aggressive breast tumor growth in vivo. However, we are unable to assess the dependency on stromal RAGE in vivo as we found that the Met1 breast tumor cells do not grow in RAGE null mice. To address this, we are performing 1) co-injections studies in RAGE null mice with breast tumor cells and primary fibroblasts isolated from wildtype mice to ask whether fibroblast RAGE is sufficient for tumor initiation and AGE-mediated breast tumor growth; and 2) co-injection studies in wildtype mice with breast tumor cells and primary fibroblasts isolated from RAGE null mice to ask whether fibroblast RAGE is necessary for AGE-mediated tumor growth. Future studies with RAGE flox mice are planned to assess the impact of dietary AGE on tumor growth in mice with fibroblast specific deletion of RAGE. Based on the importance of MYC in breast cancer and its role as a downstream effector of AGE-RAGE signaling, we hypothesized that MYC may be required for the AGE-mediated effects on epithelial cellular migration. Therefore, we inhibited MYC in fibroblasts through transfection of shMYC constructs, lentiviral infection of shMYC virus and pharmacologically with small molecule inhibitors. These fibroblasts were then used in the epithelial migration co-culture assays. We found that inhibition of MYC in fibroblasts negated the AGE-mediated effects on epithelial cell migration similar to that observed with fibroblasts lacking RAGE. We are now assessing whether MYC is required for AGE-mediated fibroblast activation. Our current data support the idea that AGE-RAGE signaling activates a MYC transcriptional program in fibroblasts to promote epithelial cell migration. Taken together, these data support the idea that dietary intervention in young women may reduce breast cancer risk. Citation Format: Gowtami Aishwarya Panguluri, Bradley A Krisanits, Jackson Lane, David P Turner, and Victoria J Findlay. Dietary-Advanced Glycation End products and breast cancer risk: Evaluating MYC dependency within the context of AGE-RAGE signaling in cancer associated fibroblasts [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-04-15.

Coal–oxygen reaction theory, which is widely accepted, considers the reaction of coal and oxygen during combustion. In this research, the characteristics of spontaneous coal combustion were assessed at a high temperature to investigate the internal relationship between the gaseous products of this reaction and the functional groups in coal molecules and to further reveal the micro-characteristics of spontaneous coal combustion. Our self-developed temperature-programmed experimental system and in situ diffuse reflectance infrared Fourier transform spectroscopy were adopted to analyze the correlation between the contents of gaseous products and active functional groups. Results reveal that the contents of indicator gases, such as CO and C2H4, increase and show a parabolic curve. In terms of active functional groups, as temperature increases, the content of aliphatic hydrocarbons initially increases and then decreases gradually. The content of C=C groups decreases throughout this study, and the content of oxygen-containing functional groups gradually increases after equilibrium is reached. Five characteristic temperatures are obtained on the basis of the variation in gaseous products, and four oxidation stages are further divided. The relationship between active functional groups and gases during different temperature stages is determined. At the critical temperature stage, the main active functional group affecting the release of CO, CO2, CH4, and C2H6 is carbonyl. Numerous alkyl chains and bridge bonds are broken at the crack‒active‒speedup temperature stage, and the primary active functional groups influencing the gas products are aliphatic hydrocarbons and carbonyl groups. The concentration of gases at the speedup‒ignition temperature stage is negatively correlated with carbonyl and carboxyl groups. Therefore, the crack‒active‒speedup temperature stage in high-temperature oxidation is dangerous, and oxidation should be controlled before this stage to reduce the loss of personnel and materials.

Progress in real-time, simultaneous in vivo detection of multiple neurotransmitters will help accelerate advances in neuroscience research. The need for development of probes capable of stable electrochemical detection of rapid neurotransmitter fluctuations with high sensitivity and selectivity and sub-second temporal resolution has, therefore, become compelling. Additionally, a higher spatial resolution multi-channel capability is required to capture the complex neurotransmission dynamics across different brain regions. These research needs have inspired the introduction of glassy carbon (GC) microelectrode arrays on flexible polymer substrates through carbon MEMS (C-MEMS) microfabrication process followed by a novel pattern transfer technique. These implantable GC microelectrodes provide unique advantages in electrochemical detection of electroactive neurotransmitters through the presence of active carboxyl, carbonyl, and hydroxyl functional groups. In addition, they offer fast electron transfer kinetics, capacitive electrochemical behavior, and wide electrochemical window. Here, we combine the use of these GC microelectrodes with the fast scan cyclic voltammetry (FSCV) technique to optimize the co-detection of dopamine (DA) and serotonin (5-HT) in vitro and in vivo. We demonstrate that using optimized FSCV triangular waveform at scan rates ≤700 V s-1 and holding and switching at potentials of 0.4 and 1 V respectively, it is possible to discriminate voltage reduction and oxidation peaks of DA and 5-HT, with 5-HT contributing distinct multiple oxidation peaks. Taken together, our results present a compelling case for a carbon-based MEA platform rich with active functional groups that allows for repeatable and stable detection of electroactive multiple neurotransmitters at concentrations as low as 1.1 nM.

Synthesis of bacterial cell surface l-glycero-d-manno-heptose (l,d-Hep)- and d-glycero-d-manno-heptose (d,d-Hep)-containing higher carbon sugars is a challenging task. Here, we report a convenient and efficient approach for the synthesis of the l,d-Hep and d,d-Hep building blocks. Using l-lyxose and d-ribose as starting materials, this approach features diastereoselective Mukaiyama-type aldol reactions as the key steps. On the basis of the synthetic l,d-Hep and d,d-Hep building blocks, we achieved the first stereoselective synthesis of the unique α-l,d-Hep-(1→3)-α-d,d-Hep-(1→5)-α-Kdo core trisaccharide of the lipopolysaccharide of Vibrio parahemolyticus O2.

In compliance with Kishi's empirical rule, catalytic osmylation of methyl [methyl (E)-2,3,4-tri-O-benzyl-6,7-dideoxy-α-D-gluco-oct-6-enopyranosid]uronate (6) produced a mixture of methyl (methyl 2,3,4-tri-O-benzyl-β-L-threo-D-gluco-octopyranosid)uronate (9) and the corresponding α-D-threo-D-gluco isomer (10) in the ratio ca. 9 : 1, respectively. Similar osmylation of the (E)-D-manno-octenopyranosiduronate (8) furnished a mixture of methyl (methyl 2,3,4-tri-O-benzyl-β-L-threo-D-manno-octopyranosid)uronate (12) and the corresponding α-D-threo-D-manno isomer (13) in the ratio ca. 6 : 1. In each instance, the stereoselectivity of the osmylation reaction for the (E)-octenopyranosiduronate is higher than that of the corresponding (E)-octenopyranoside. The catalytic osmylation of methyl (E)-3,5-O-benzylidene-6,7-dideoxy-1,2-O-isopropylidene-α-D-gluco-oct-6-enofuranuronate (24), on the other hand, breached Kishi's empirical rule to provide a mixture of methyl 3,5-O-benzylidene-1,2-O-isopropylidene-α-D-threo-D-gluco-octofuranuronate (25) and the corresponding β-L-threo-D-gluco isomer (26) in the ratio ca. 2 : 1, respectively. Acid hydrolysis of the protected octofuranose (27) obtained from the octofuranuronate (25), and reduction of the resulting octose gave the new octitol (meso)-threo-gluco-octitol (28). The stereochemistry of the osmylation product (26) was established by X-ray crystallography.

Herein we report a short and efficient protocol for the synthesis of naturally occurring higher‐carbon sugars—sedoheptulose (d‐altro‐hept‐2‐ulose) and d‐glycero‐l‐galacto‐oct‐2‐ulose—from readily available sugar aldehydes and dihydroxyacetone (DHA). The key step includes a diastereoselective organocatalytic syn‐selective aldol reaction of DHA with d‐erythrose and d‐xylose, respectively. The methodology presented can be expanded to the synthesis of various higher sugars by means of syn‐selective carbon–carbon‐bond‐forming aldol reactions promoted by primary‐based organocatalysts. For example, this methodology provided useful access to d‐glycero‐d‐galacto‐oct‐2‐ulose and 1‐deoxy‐d‐glycero‐d‐galacto‐oct‐2‐ulose from d‐arabinose in high yield (85 and 74 %, respectively) and high stereoselectivity (99:1).

The convenient route (showing a historical background of the co-operation between the author and late Professor Aleksander Zamojski) to carbocyclic sugar mimics: derivatives of highly oxygenated bicyclo[4.3.0]nonanes and bicyclo[ 4.4.0]decanes from sugar chirons is presented. First, the paper describes the stereoselective synthesis of higher carbon sugars (up to 21 carbon atoms in the chain) starting from various simple derivatives of carbohydrates such as: sugar phosphoranes and phosphonates, sugar acetylenes, and finally sugar allyltins. The latter turned to be convenient starting materials for the preparation of highly versatile dienoaldehydes, via a controlled fragmentation with elimination of the stannyl moiety. These dienes were used for the stereoselective synthesis of highly oxygenated carbo-bicyclic derivatives.