Synthetic Studies Research Articles

Stereo-divergent Synthesis of Nonproteinogenic Amino Acids and Synthetic Study for Biologically Active Cyclopeptides

Naturally occurring cyclopeptides are potential middle-molecule drug candidates beyond Lipinski's rule of five. This paper focuses on the structural determination and structure-activity relationship (SAR) study of two cyclopeptides: asperterrestide A and decatransin. The proposed asperterrestide A was synthesized by solution-phase peptide elongation, followed by macrolactamization. NMR analysis and molecular modeling studies revealed the stereochemistry at the two α-positions of amino acid residues as opposite to each other. This was further confirmed by the total synthesis of the revised asperterrestide A. SAR study of synthetic products revealed that the β-hydroxy group in the nonproteinogenic amino acid residue was not essential for its cytotoxicity. In addition, N-alkyl-enriched peptide fragments of decatransin were synthesized in solution-phase without diketopiperadine formation. The putative candidates of decatransin was synthesized by convergent peptide coupling, followed by macrocyclization under modified Mitsunobu conditions. The structure of the natural decatransin, including its absolute configuration, was determined through a comparison of spectral data and the cytotoxicity exhibited by the synthetic products.

A π‐Extension Process from 9‐Phosphaanthracene Leading to Phosphatetraphenes and Phosphatetracenes

AbstractExtension of π‐system with phosphinine (phosphorine, phosphabenzene) has been of interest because of the expected higher HOMO and lower LUMO levels compared with the corresponding carbon congeners. In this paper, a π‐extension process based on the 9‐phosphaanthracene skeleton was demonstrated by synthesizing 12‐phosphatetraphene and 9‐phosphabenzo[f]tetraphene by utilizing the deaminative aromatization pathway. Starting from 3,5‐bis(trifluoromethyl)aniline, we developed the dibromotriarylmethane precursors containing the 3,5‐bis(trifluoromethyl)‐2‐bromophenyl unit, which would be slightly effective to increase the steric congestion around the fragile P=C bonds incorporated in the fused polyaromatic skeletons. The bis‐trifluoromethyl 12‐phosphatetraphenes have been synthesized together with the mono‐trifluoromethyl derivative, and the planar 12‐phosphatetraphene skeleton was confirmed. On the other hand, the CF3‐substituted 9‐phosphabenzo[f]tetraphene displayed a remarkably twisted fused five ring system leading to the wavy structures incorporating phosphinine. Also, synthetic study of 5‐phosphatetracene using the bis(trifluoromethyl)phenyl unit was attempted and the incomplete elimination of the amine indicated labile characters of the observed phosphorus congener of tetracene. The findings of this study would be informative for developing heavier congeners of polyaromatic hydrocarbons (PAHs) as well as the trifluromethyl effects.

Biomimetic Transition Metal Cluster Complexes: Synthetic Studies and Applications in the Reduction of Inert Small Molecules

Abstract Transition metal cluster complexes, particularly those containing iron and sulfur, are used as catalysts for the biological reduction of inert small molecules such as N2 and CO2. The structures of these biological clusters are complicated and the protein backbones around the clusters often play important roles in catalysis, hence reproducing or mimicking the enzymatic functions with synthetic cluster complexes remains a challenge. Appropriate assumptions and hypotheses on the relationships between the structures and functions of biological clusters are needed to develop synthetic molecular catalysts inspired by enzymes. This account reviews recent studies by the author and his coworkers on iron-containing biomimetic cluster complexes. Cubic Mo-Fe-S clusters supported by bulky cyclopentadienyl ligands on molybdenum were designed and synthesized, and their Fe sites captured and catalytically converted N2 under reducing conditions. Iron-hydride clusters, which are relevant to the active species of biological and industrial nitrogen fixation, also served as catalysts for the reduction of N2. Furthermore, various metal-sulfur clusters, ranging from a structural mimic of the complex active site of the N2-reducing enzyme to a simple and cubic [Fe4S4] cluster, were found to catalyze the biologically inaccessible direct conversion of CO2 to short-chain hydrocarbons. These studies have demonstrated the potential utility of biomimetic approaches to the catalytic reduction of inert small molecules, through the rational design and synthesis of simple yet appropriate iron-containing cluster complexes.

A Combined Synthetic, Magnetic, and Theoretical Study on Enhancing Ligand-Field Axiality for Dy(III) Single-Molecule Magnets Supported by Ferrocene Diamide Ligands.

Molecular design is crucial for improving the performance of single-molecule magnets (SMMs). For dysprosium(III) SMMs, enhancing ligand-field axiality is a well-suited strategy to achieve high-performance SMMs. We synthesized a series of dysprosium(III) complexes, (NNTIPS)DyBr(THF)2 (1, NNTIPS = fc(NSiiPr3)2; fc = 1,1'-ferrocenediyl, THF = tetrahydrofuran), [(NNTIPS)Dy(THF)3][BPh4] (2), (NNTIPS)DyI(THF)2 (3), and [(NNTBS)Dy(THF)3][BPh4] (4, NNTBS = fc(NSitBuMe2)2), supported by ferrocene diamide ligands. X-ray crystallography shows that the rigid ferrocene backbone enforces a nearly axial ligand field with weakly coordinating equatorial ligands. Dysprosium(III) complexes 1-4 all exhibit slow magnetic relaxation under zero fields and possess high effective barriers (Ueff) around 1000 K, comparable to previously reported (NNTBS)DyI(THF)2 (5). We probed the influences of structural variations on SMM behaviors by theoretical calculations and found that the distribution of negative charges defined by rq, i.e., the ratio of the charges on the axial ligands to the charges on the equatorial ligands, plays a decisive role. Moreover, theoretical calculations on a series of model complexes 1'-5' without equatorial ligands unveil that the axial crystal-field parameters B20 are directly proportional to the N-Dy-N angles and support the hypothesis that enhancing the ligand-field axiality could improve SMM performance.

Synthetic Studies toward the Myrioneuron Alkaloids.

The Myrioneuron alkaloids are a relatively small family of plant-derived alkaloids that present an intriguing array of structural intricacy and biological properties. As such, these natural products have drawn interest from the synthetic community, resulting in creative total syntheses of several family members. This review showcases recent synthetic efforts towards these polycyclic alkaloids.

Electronic Impurity Doping of a 2D Hybrid Lead Iodide Perovskite by Bi and Sn

Control over conductivity and carrier type (electrons and holes) defines semiconductors. A primary approach to target carrier concentrations involves introducing a small population of aliovalent impurity dopant atoms. In a combined synthetic and computational study, we assess impurity doping by introducing Bi and Sn into the prototype 2D Ruddlesden-Popper hybrid perovskite phenylethylammonium lead iodide (PEA2PbI4). Experimentally, we demonstrate that Bi and Sn can achieve n- and p-type doping, respectively, but the doping efficiency is low. Simulations show that Bi introduces a deep defect energy level (∼0.5 eV below the conduction band minimum) that contributes to the low doping efficiency, but, to reproduce the low doping efficiency observed experimentally, an acceptor level must also be present that limits n-type doping. Experiments find that Sn achieves p-dopant behavior and simulations suggest that this occurs through the additional oxidation of Sn defects. We also study how substitutional Bi incorporation can be controlled by tuning the electrochemical environment during synthesis. First-principles impurity doping simulations can be challenging; typical dopant concentrations constitute less than 0.01% of the atoms, necessitating large supercells, while a high level of theory is needed to capture the electronic levels. We demonstrate simulations of complex defect-containing unit cells that include up to 3383 atoms, employing spin-orbit coupled hybrid density functional theory. While p- and n-type behavior can be achieved with Sn and Bi, simulations and experiments provide concrete directions where future efforts must be focused to achieve higher doping efficiency.Received 5 December 2022Revised 28 April 2023Accepted 4 May 2023DOI:https://doi.org/10.1103/PRXEnergy.2.023010Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI. Open access publication funded by the National Renewable Energy Laboratory (NREL) Library, part of a national laboratory of the U.S. Department of Energy.Published by the American Physical SocietyPhysics Subject Headings (PhySH)Research AreasEnergy materialsSolar energyEnergy Science & Technology

First-arrival traveltime tomography for monitoring the excavation damaged zone in the Horonobe Underground Research Laboratory

Subsurface excavation results in the formation of a zone called excavation damaged zone (EDZ) around the tunnel wall. An EDZ is a major concern in the field of high-level radioactive waste disposal because it may act as a flow path after the closure of a repository. In this study, first-arrival traveltime tomography was repeatedly conducted on the EDZ at a depth of 350 ​m in the Horonobe Underground Research Laboratory. However, the acquired data was highly affected by the support structure on the drift wall. For proper visualization of the EDZ, information about the structure was incorporated into the inversion by modifying the model constraint. The synthetic study showed that the approach reproduced the EDZ in the model without the artifacts. The method was applied to field data, and the EDZ around the drift was detected. The inversion was extended to a time-lapse inversion to trace the changes in P-wave velocity in the EDZ. The synthetic study demonstrated that temporal changes in the P-wave velocity distribution could be detected. Data obtained from 12 surveys under open-drift conditions were analyzed by time-lapse inversion. The results indicated that the EDZ did not undergo sealing or evolution at the site for approximately seven years.

Autonomous construction safety incentive mechanism using blockchain-enabled tokens and vision-based techniques

Current incentive mechanisms for construction safety highly rely on intermediaries and massive paperwork, which lay a foundation for opportunistic behavior and poor performance in the long run. As a solution, this study introduces an automatic incentive mechanism that rewards contractors with Fungible Tokens (FTs) and Non-Fungible Tokens (NFTs). Visual data of construction sites is processed through a computer-vision module, which reports safety performance. These reports are evaluated in a network of smart contracts, using a decentralized oracle network (DON), and token-based rewards are determined and distributed accordingly. Users can redeem their FT rewards or NFTs through an interactive front-end portal. The proposed method is successfully implemented through a synthetic case study to prove its feasibility. The proposed decentralized application (Dapp) provides a transparent, traceable, and immutable incentive mechanism that improves trust among stakeholders, and can be used as a template and expanded to fields beyond construction safety.

BioAutoMATED: An end-to-end automated machine learning tool for explanation and design of biological sequences.

The design choices underlying machine-learning (ML) models present important barriers to entry for many biologists who aim to incorporate ML in their research. Automated machine-learning (AutoML) algorithms can address many challenges that come with applying ML to the life sciences. However, these algorithms are rarely used in systems and synthetic biology studies because they typically do not explicitly handle biological sequences (e.g., nucleotide, amino acid, or glycan sequences) and cannot be easily compared with other AutoML algorithms. Here, we present BioAutoMATED, an AutoML platform for biological sequence analysis that integrates multiple AutoML methods into a unified framework. Users are automatically provided with relevant techniques for analyzing, interpreting, and designing biological sequences. BioAutoMATED predicts gene regulation, peptide-drug interactions, and glycan annotation, and designsoptimized synthetic biology components, revealing salient sequence characteristics. By automating sequence modeling, BioAutoMATED allows life scientists to incorporate ML more readily into their work.

Synthetic Study toward Triterpenes from the Schisandraceae Family of Natural Products.

Triterpenoid natural products from the Schisandraceae family have long presented a significant synthetic challenge. Lancifodilactone I, a member of the family not previously synthesized, was identified as a key natural product target, from which many other members could be synthesized. We envisaged that the core ring system of lancifodilactone I could be accessed by a strategy involving palladium-catalysed cascade cyclisation of a bromoenynamide, via carbopalladation, Suzuki coupling and 8π-electrocyclisation, to synthesize the core 7,8-fused ring system. Exploration of this strategy on model systems resulted in efficient syntheses of 5,6- and 5,8-fused systems in high yields, which represent the first such cyclisation where the ynamide nitrogen atom is 'external' to the forming ring system. The enamide functionality resident in the cascade cyclisation product was found to be less nucleophilic than the accompanying tri-/tetrasubstituted alkene(s), enabling regioselective oxidations. Application of this strategy to 7,6-, and 7,8-fused systems, and ultimately the 'real' substrate, was ultimately thwarted by the difficulty of 7-membered ring closure, leading to side product formation. Nevertheless, a tandem bromoenynamide carbopalladation, Suzuki coupling and 6/8π-electrocyclisation was shown to be a highly efficient tactic for the formation of bicyclic enamides, which may find applications in other synthetic contexts.

Formation of Heterobimetallic Complexes by Addition of d10-Metal Ions to [(Me3P)xM(2-C6F4PPh2)2] (x = 1, 2; M = Ni and Pt): A Synthetic and Computational Study of Metallophilic Interactions.

Treatment of the bis(chelate) complexes trans-[M(κ2-2-C6F4PPh2)2] (trans-1M; M = Ni, Pt) and cis-[Pt(κ2-2-C6F4PPh2)2] (cis-1Pt) with equimolar amounts or excess of PMe3 solution gave complexes of the type [(Me3P)xM(2-C6F4PPh2)2] (x = 2: 2Ma, 2Mb x = 1: 3Ma, 3Mb; M = Ni, Pt). The reactivity of complexes of the type 2M and 3M toward monovalent coinage metal ions (M' = Cu, Ag, Au) was investigated next to the reaction of 1M toward [AuCl(PMe3)]. Four different complex types [(Me3P)2M(μ-2-C6F4PPh2)2M'Cl] (5MM'; M = Ni, Pt; M' = Cu, Ag, Au), [(Me3P)M(κ2-2-C6F4PPh2)(μ-2-C6F4PPh2)M'Cl]x (x = 1: 6MM'; M = Pt; M' = Cu, Au; x = 2: 6PtAg), head-to-tail-[(Me3P)ClM(μ-2-C6F4PPh2)2M'] (7MM'; M = Ni, Pt; M' = Au), and head-to-head-[(Me3P)ClM(μ-2-C6F4PPh2)2M'] (8MM'; M = Ni, Pt; M' = Cu, Ag, Au) were observed. Single-crystal X-ray analyses of complexes 5-8 revealed short metal-metal separations (2.7124(3)-3.3287(7) Å), suggestive of attractive metal-metal interactions. Quantum chemical calculations (atoms in molecules (AIM), electron localization function (ELF), non-covalent interaction (NCI), and natural bond orbital (NBO)) gave theoretical support that the interaction characteristics reach from a pure attractive non-covalent to an electron-shared (covalent) character.

Synthetic Studies to exo‐Ring‐Junction based Fused 5/5/n‐Tricyclic Systems: Access to A, B, C‐Ring System of Longeracinphyllin A, Himalenine D, and Daphnipaxiamine A.

AbstractWe report a short synthetic approach to various tricyclic systems that are present in several diquinane‐based natural products starting with a readily available exo‐dicyclopentadiene‐1‐one. To this end, we have successfully assembled a fused 5/5/7‐tricyclic enone via ring‐rearrangement metathesis as a key step. The strategy has been further extended to synthesize the 1,3‐dihydroxy and then 1‐keto‐3‐hydroxy derivatives by utilizing regio‐ and stereoselective epoxidation and ring‐rearrangement metathesis reactions as key steps. All these target compounds are found to be present in diquinane‐based natural products such as longeracinphyllins A, himalenine D and daphnipaxianine A, etc. Moreover, the newly synthesized tricyclic compounds matches the exact ring‐junction stereochemistry (5/5‐exo) of these natural products. Hence, the synthetic studies disclosed here may be useful in the synthesis of biologically significant natural products and in the drug design. The newly synthesized molecules were characterized by NMR and HRMS data. Some of these structures were confirmed by a single crystal X‐ray diffraction studies.

Highlights on the General Preference for Multi-Over Mono-Coupling in the Suzuki–Miyaura Reaction

A systematic synthetic study was performed to explain the usual trend in selectivity towards multi-coupling, over mono-coupling, in Suzuki–Miyaura reactions. This preference was observed under different reaction conditions: for various halobenzenes, using substituents on the boronic acid, and changing the catalyst and temperature. Moreover, this reaction selectivity was found to increase for more reactive systems towards oxidative addition and more diluted media. The results constitute experimental evidence that the formation of the totally substituted coupling product is kinetically favoured by a reaction path location—the proximity between the regenerated catalyst and the newly formed coupling intermediate promotes the subsequent reaction.

Synthesis of immunostimulatory saponins: A sweet challenge for carbohydrate chemists

Saponins are a large family of natural glycosides showing a wide range of biological activities. Current research efforts on saponins as vaccine adjuvants have been mainly focused on the development of synthetic analogs. By mimicking the immunomodulatory saponins from Quillaja saponaria (QS), less complex and readily accessible analogs have been synthesized to improve the industrial applicability and efficacy of saponins as vaccine adjuvants. Through the exploration of several structural modifications on the skeleton of QS saponins, including changes in the sugar and aglycone compositions as well as in the nature and configuration of the glycosidic bonds, structure-activity relationship (SAR) studies developed by Pr. Gin in the early 2010s were taken as a starting point for the development of a new generation of immunomodulatory candidates. In this review, the recent synthetic strategies and SAR studies of mono- and bidesmosidic QS saponins are discussed. Original concepts of vaccination including self-adjuvanticity and the development of saponin-based glycoconjugates are described. The synthesis and semi-synthesis of saponin alternatives to QS, such as Momordica saponin and onjisaponin derivatives, are also discussed in this review.

Cased-hole reverse time migration imaging using ultrasonic pitch-catch measurement: Theory and synthetic case studies

Cement-bond evaluation is of great significance in oil/gas development, geothermal production, and CO2 storage. Advanced ultrasonic pitch-catch measurement exhibits poor performance in determining a cement-formation interface due to weak reflections from the cement-formation interface (third interface echo) in nonaxisymmetric complex ultrasonic environments. To deal with this issue, we use a reverse time migration (RTM) approach for ultrasonic pitch-catch measurements to image the cased-hole structure, especially for the cement-formation interface. To further enhance cased-hole RTM feasibility, a phase-shift interpolation technique is applied to reconstruct ultrasonic array waveforms from limited receivers in the pitch-catch measurement. Synthetic examples demonstrate that RTM is capable of imaging the cement-formation interface with a high resolution under various eccenterings of casings and tools. This study illustrates that small errors introduced by phase-shift interpolations do not greatly degrade the imaging result of RTM. Furthermore, tests for inclined cement-formation interfaces demonstrate that the RTM is able to recover the true position and geometry of the cement-formation interface when a smoothed velocity model is available. In addition, although RTM is sensitive to the velocity perturbation, it is possible to image the cased-hole structure by using a multistep strategy assuming that the position and thickness of the steel casing are unknown.

Design and Identification of Inhibitors for the Spike-ACE2 Target of SARS-CoV-2.

When an epidemic started in the Chinese city of Wuhan in December 2019, coronavirus was identified as the cause. Infection by the virus occurs through the interaction of viral S protein with the hosts' angiotensin-converting enzyme 2. By leveraging resources such as the DrugBank database and bioinformatics techniques, ligands with potential activity against the SARS-CoV-2 spike protein were designed and identified in this investigation. The FTMap server and the Molegro software were used to determine the active site of the Spike-ACE2 protein's crystal structure. Virtual screening was performed using a pharmacophore model obtained from antiparasitic drugs, obtaining 2000 molecules from molport®. The ADME/Tox profiles were used to identify the most promising compounds with desirable drug characteristics. The binding affinity investigation was then conducted with selected candidates. A molecular docking study showed five structures with better binding affinity than hydroxychloroquine. Ligand_003 showed a binding affinity of -8.645 kcal·mol-1, which was considered an optimal value for the study. The values presented by ligand_033, ligand_013, ligand_044, and ligand_080 meet the profile of novel drugs. To choose compounds with favorable potential for synthesis, synthetic accessibility studies and similarity analyses were carried out. Molecular dynamics and theoretical IC50 values (ranging from 0.459 to 2.371 µM) demonstrate that these candidates are promising for further tests. Chemical descriptors showed that the candidates had strong molecule stability. Theoretical analyses here show that these molecules have potential as SARS-CoV-2 antivirals and therefore warrant further investigation.

Systematic Large Fragment Deletions in the Genome of Synechococcus elongatus and the Consequent Changes in Transcriptomic Profiles.

Genome streamlining, as a natural process in the evolution of microbes, has become a common approach for generating ideal chassis cells for synthetic biology studies and industrial applications. However, systematic genome reduction remains a bottleneck in the generation of such chassis cells with cyanobacteria, due to very time-consuming genetic manipulations. Synechococcus elongatus PCC 7942, a unicellular cyanobacterium, is a candidate for systematic genome reduction, as its essential and nonessential genes have been experimentally identified. Here, we report that at least 20 of the 23 over 10 kb nonessential gene regions could be deleted and that stepwise deletions of these regions could be achieved. A septuple-deletion mutant (genome reduced by 3.8%) was generated, and the effects of genome reduction on the growth and genome-wide transcription were investigated. In the ancestral triple to sextuple mutants (b, c, d, e1), an increasingly large number of genes (up to 998) were upregulated relative to the wild type, while slightly fewer genes (831) were upregulated in the septuple mutant (f). In a different sextuple mutant (e2) derived from the quintuple mutant d, much fewer genes (232) were upregulated. Under the standard conditions in this study, the mutant e2 showed a higher growth rate than the wild type, e1 and f. Our results indicate that it is feasible to extensively reduce the genomes of cyanobacteria for generation of chassis cells and for experimental evolutionary studies.

Synthesis, structural characterization, and antibacterial activity of alkenyl functionalized imidazolium N-heterocyclic silver(I) and gold(I) carbene complexes

Synthetic, structural, and antibacterial studies of a series of functionalized monocarbene NHC of silver(I) and gold(I) complexes are reported. Silver NHC compounds of general formula [AgCl{NHC}] 1a–e have been obtained in excellent yields by the traditional synthetic method using Ag2O, as starting material, and the corresponding 3-substituted 1-(2-methylallyl)imidazolium chloride salts L1–L5. NHC–Ag(I) compounds 1a–e were used as transmetalation agents to synthesize monocarbenes NHC–Au(I) complexes [AuCl{NHC}] 2a–e in good yields by using [AuCl(SMe2)] as a source of gold (I). All compounds were characterized by spectroscopic and analytic techniques. The molecular structures of seven compounds L3, 1a, 1d, 2a, 2a′, 2c and 2d were confirmed by a single-crystal X-ray diffraction method. Elemental analysis and powder X-ray diffraction (PXRD) experimental studies were also carried out. In addition, in vitro antibacterial assays, of the series NHC–Ag(I) 1a–e and NHC–Au(I) 2a–e were tested against three Gram positives: Staphylococcus aureus, Bacillus subtilis, and Enterococcus faecalis, and three Gram negatives: Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi bacterial strains by Kirby–Bauer’s disk diffusion method. Silver compounds 1a, 1d, and all gold compounds showed excellent activity against S. aureus and S. typhi, though both types of complexes showed antibacterial activity, gold complexes were found to be the most active antibacterials. Good activity was shown by complexes 1a and 1d against P. aerouginosa, E. coli, S. typhi, S. aureus and E. feacalis and compounds 2b and 2e against E. faecalis. An excellent activity was shown by compound 2a against S. aureus with the highest inhibitory zone of 26 ± 0 mm.

Przestrzenne cechy transgranicznej współpracy turystycznej w regionie Morza Bałtyckiego = Spatial features of cross-border tourist cooperation in the Baltic Sea Region

This article aims to explain where the cross-border tourism cooperation in the Baltic Sea Region (BSR) can be observed, and its specifical aim is to answer the research question: What are the spatial characteristics of cooperation in cross-border tourism projects in the Baltic Sea Region? Using the methods of spatial analysis in GIS, statistical methods and analysis of project documents, synthetic research was carried out on the cooperation of beneficiaries of tourism projects under the Interreg IV A, B and C programs in the BSR. The spatial nature of this cooperation was presented in a descriptive and cartographic form, taking into account the locations of beneficiaries, budgets, roles in the project, concentration, connections and topics of their cooperation. Although the empirical study presented below is limited only to tourism cooperation under the EU-funded Interreg IV program in the BSR, it is one of the first studies on cross-border cooperation between entities separated by a sea border in general, as well as one of the first synthetic studies on projects from different levels of European Union funding in the Interreg program (A, B and C), which cover a larger area of research. Cooperation is measured by number and distance of the relations between the beneficiaries. Comparison of the number of implemented projects related to tourism, the number of beneficiaries, the average amount of beneficiaries' budgets and their concentration showed diametrical differences in the region between its western and eastern parts. It can therefore be said that the "Iron Curtain" is still visible, which in the second half of the 20th century divided the south-eastern part of the Baltic Sea from its north-western part

Stereospecific naphthoquinone photoredox reactions: Total syntheses of spirocyclic natural products

This account outlines our recent studies on the photoredox reaction of naphthoquinones. The mechanism consists of three consecutive events triggered by photo-irradiation, (1) hydrogen abstraction by the excited quinone to generate a biradical species, (2) internal single electron transfer (SET) to convert the biradical to the corresponding zwitterion, and (3) oxy-cyclization to give the product. The overall process allows replacement of a C–H bond by a C–O bond in a stereospecific, retentive manner. This photo-induced reaction has a broad scope, enabling otherwise-difficult stereocontrolled synthesis of natural products, as demonstrated by the syntheses of two classes of antibiotics, the spiroxins and the preussomerins. The former targets feature stereogenic spirocyclic ether structures, which were effectively constructed by a photoredox reaction involving 1,5-HAT, while the latter targets featuring stereogenic acetal structures were constructed by a photoredox reaction involving 1,6-HAT. Also described is the synthetic study of the rubromycins, centering attention to the stereospecific construction of the spiroacetal center.