The Sugar Cube

Science

The Sugar Cube: Network Control and Emergence in Stereoediting Reactions

H. M. Carder,^† G. Occhialini,^† G. Bistoni, C. Riplinger, E. E. Kwan* & A. E. Wendlandt*

Science 2024, 385, 456–463 (DOI: 10.1126/science.adp2447)

Stereochemical editing strategies have recently enabled the transformation of readily accessible substrates into rare and valuable products. Typically, site selectivity is achieved by minimizing kinetic complexity by using protecting groups to suppress reactivity at undesired sites (substrate control) or by using catalysts with tailored shapes to drive reactivity at the desired site (catalyst control). The authors propose “network control,” a contrasting paradigm that exploits hidden interactions between rate constants to greatly amplify modest intrinsic biases and enable precise multisite editing. When network control is applied to the photochemical isomerization of hexoses, six of the eight possible diastereomers can be selectively obtained. The amplification effect can be viewed as a mesoscale phenomenon between the limiting regimes of kinetic control in simple chemical systems and metabolic regulation in complex biological systems.

Asymmetric Photoenzymatic Incorporation of Fluorinated Motifs into Olefins

M. Li, Y. Yuan, W. Harrison, Z. Zhang & H. Zhao*

Science 2024, 385, 416–421 (DOI: 10.1126/science.adk8464)

Enzymes capable of assimilating fluorinated feedstocks are scarce. This situation poses a challenge for the biosynthesis of fluorinated compounds used in pharmaceuticals, agrochemicals, and materials. The authors developed a photoenzymatic hydrofluoroalkylation that integrates fluorinated motifs into olefins. The photoinduced promiscuity of flavin-dependent ene-reductases enables the generation of carbon-centered radicals from iodinated fluoroalkanes, which are directed by the photoenzyme to engage enantioselectively with olefins. This approach facilitates stereocontrol through interaction between a singular fluorinated unit and the enzyme, securing high enantioselectivity at β, γ, or δ positions of fluorinated groups through enzymatic hydrogen atom transfer—a process that is notably challenging with conventional chemocatalysis.

Nature Communications

Water Mediated Redox-Neutral Cleavage of Arylalkenes via Photoredox Catalysis

K. Liao,^† Y. Fang,^† L. Sheng, J. Chen* & Y. Huang*

Nat. Commun. 2024, 15, 6227 (DOI: 10.1038/s41467-024-50624-2) 🔓

Cleavage of carbon-carbon bonds remains a challenging task in organic synthesis. Traditional methods for splitting Csp² =Csp² bonds into two halves typically involve non-redox (metathesis) or oxidative (ozonolysis) mechanisms, limiting their synthetic potential. Disproportionative deconstruction of alkenes, which yields one reduced and one oxidized fragment, remains an unexplored area. In this study, the authors introduce a redox-neutral approach for deleting a Csp² carbon unit from substituted arylalkenes, resulting in the formation of an arene (reduction) and a carbonyl product (oxidation). This transformation is believed to proceed through a mechanistic sequence involving visible-light-promoted anti-Markovnikov hydration, followed by photoredox cleavage of Csp³ -Csp³ bond in the alcohol intermediate. A crucial consideration in this design is addressing the compatibility between the highly reactive oxy radical species in the latter step and the required hydrogen-atom-transfer (HAT) reagent for both steps. The authors found that ethyl thioglycolate serves as the optimal hydrogen-atom shuttle, offering remarkable chemoselectivity among multiple potential HAT events in this transformation. By using D₂O, they successfully prepared dideuteromethylated (-CD₂H) arenes with good heavy atom enrichment.

Journal of the American Chemical Society

Concise Total Syntheses of (−)-Crinipellins A and B Enabled by a Controlled Cargill Rearrangement

B. Xu,^† Z. Zhang,^† D. J. Tantillo* & M. Dai*

J. Am. Chem. Soc. 2024, ASAP (DOI: 10.1021/jacs.4c07900) 🔓

The authors report concise total syntheses of diterpene natural products (−)-crinipellins A and B with a tetraquinane skeleton, three adjacent all-carbon quaternary centers, and multiple oxygenated and labile functional groups. The synthesis features a convergent Kozikowski β-alkylation to unite two readily available building blocks with all the required carbon atoms, an intramolecular photochemical [2+2] cycloaddition to install three challenging and adjacent all-carbon quaternary centers and a 5–6–4–5 tetracyclic skeleton, and a controlled Cargill rearrangement to rearrange the 5–6–4–5 tetracyclic skeleton to the desired tetraquinane skeleton. These strategically enabling transformations allowed the authors to complete total syntheses of (−)-crinipellins A and B in 12 and 13 steps, respectively. The results of quantum chemical computations revealed that the Bronsted acid-catalyzed Cargill rearrangements likely involve stepwise paths to products and the AlR₃-catalyzed Cargill rearrangements likely involve a concerted path with asynchronous alkyl shifting events to form the desired product.

Cyclopropanation with Non-Stabilized Carbenes via Ketyl Radicals

D. T. Ngo,^† J. J. A. Garwood^† & D. A. Nagib*

J. Am. Chem. Soc. 2024, ASAP (DOI: 10.1021/jacs.4c07388)

A radical mechanism enables simple and robust access to nonstabilized, alkyl iron carbenes for novel (2+1) cycloadditions. This Fe-catalyzed strategy employs simple, aliphatic aldehydes as carbene precursors in a practical, efficient, and stereoselective cyclopropanation. This air- and water-tolerant method permits convenient generation of iron carbenes and coupling to an exceptionally wide range of sterically and electronically diverse alkenes (nucleophilic, electrophilic, and neutral). A transient ketyl radical intermediate is key to accessing and harnessing this rare, alkyl iron carbene reactivity. Mechanistic experiments confirm the (a) intermediacy of ketyl radicals, (b) iron carbene formation by radical capture, and (c) nonconcerted nature of the (2+1) cycloaddition.

Total Synthesis of (−)-Rauvomine B via a Strain-Promoted Intramolecular Cyclopropanation

J. M. Aquilina, A. Banerjee, G. N. Morais, S. Chen* & M. W. Smith*

J. Am. Chem. Soc. 2024, ASAP (DOI: 10.1021/jacs.4c07669)

ChemRxiv 2024 (DOI: 10.26434/chemrxiv-2024-jp63v-v2) 🔓

The authors describe the first total synthesis of the unusual cyclopropane-containing indole alkaloid (−)-rauvomine B via a strategy centered upon intramolecular cyclopropanation of a tetracyclic N-sulfonyltriazole. Preparation of this precursor evolved through two generations of synthesis, with the ultimately successful route involving a palladium-catalyzed stereospecific allylic amination, a cis-selective Pictet–Spengler reaction, and ring-closing metathesis as important bond-forming reactions. The key cyclopropanation step was found to be highly dependent on the structure and conformational strain of the indoloquinolizidine N-sulfonyltriazole precursor, the origins of which are explored computationally through DFT studies. Overall, the synthesis proceeds in 11 total steps and 2.4% yield from commercial materials.

Total Synthesis Facilitates in vitro Reconstitution of SgvP, the C–S Bond Forming P450 in Griseoviridin Biosynthesis

C. N. Stout & H. Renata*

J. Am. Chem. Soc. 2024, ASAP (DOI: 10.1021/jacs.4c06080)

ChemRxiv 2024 (DOI: 10.26434/chemrxiv-2024-jt6g5) 🔓

Griseoviridin is a group A streptogramin natural product from Streptomyces with broad-spectrum antibacterial activity. A hybrid polyketide-non-ribosomal peptide, it comprises a 23-membered macrocycle, an embedded oxazole motif, and a macro-lactone with a unique ene-thiol linkage. Recent analysis of the griseoviridin biosynthetic gene cluster implicated SgvP, a cytochrome P450 monooxygenase, in late-stage installation of the critical C–S bond. While genetic and crystallographic experiments provided indirect evidence to support this hypothesis, the exact function of SgvP has never been confirmed bio-chemically. Herein, the authors report a convergent total synthesis of pre-griseoviridin, the putative substrate of P450 SgvP and precursor to griseoviridin. The strategy features concise and rapid assembly of two fragments joined via sequential peptide coupling and Stille macrocyclization. Access to pre-griseoviridin then enabled in vitro validation of SgvP as the C–S bond forming P450 during griseoviridin biosynthesis, culminating in a 9-step chemoenzymatic synthesis of griseoviridin.

Chemoselective Silver-Catalyzed Nitrene Transfer: Tunable Syntheses of Azepines and Cyclic Carbamimidates

E. Z. Schroeder,^† C. Lin,^† Y. Hu, Z.-Y. Dai, A. F. Griffin, T. S. Hotvedt, I. A. Guzei & J. M. Schomaker*

J. Am. Chem. Soc. 2024, ASAP (DOI: 10.1021/jacs.4c08249)

ChemRxiv 2024 (DOI: 10.26434/chemrxiv-2024-6mjmb) 🔓

Azepines and their saturated azepane counterparts are important moieties in bioactive molecules but are under-represented in current drug screening libraries. Herein, the authors report a mild and efficient azepine formation via silver-catalyzed dearomative nitrene transfer. A 2,2,2-trichloroethoxysulfonyl (Tces)-protected carbamimidate nitrene precursor, coupled with the appropriate ligand for silver, is essential for achieving the unexpected chemoselectivity between arene dearomatization and benzylic C(sp³ )–H amination. Potential applications in the late-stage diversification of azepines to complex molecular scaffolds and diastereoselective hydrogenations to sp³ -rich derivatives are also highlighted.

Rh-Catalyzed Enantioselective Single-Carbon Insertion of Alkenes

W. J. Teo,^† J. E. Guasch,^† L. Jiang, B. Li & M. G. Suero*

J. Am. Chem. Soc. 2024, ASAP (DOI: 10.1021/jacs.4c06158) 🔓

The interest in the discovery and development of skeletal editing processes that selectively insert, exchange, or delete an atom in organic molecules has significantly increased over the last few years. However, processes of this class that proceed through the creation of a chiral center with high asymmetric induction have been largely unexplored. Herein, the authors report an enantioselective single-carbon insertion in aryl- and alkyl-substituted alkenes mediated by a catalytically generated chiral Rh-carbynoid and phosphate nucleophiles that produce enantioenriched allylic phosphates (enantiomeric ratio (e.r.) = 89.5:10.5–99.5:0.5). The key to the process was a diastereo- and enantioselective cyclopropanation of the alkene with a chiral Rh-carbynoid and the formation of a transient cyclopropyl–I^(III) intermediate. The addition of the phosphate nucleophile provided a cyclopropyl–I^(III) -phosphate intermediate that undergoes disrotatory ring opening following the Woodward–Hoffmann–DePuy rules. This process led to a chiral intimate allyl cation–phosphate pair that evolved with excellent enantioretention. The authors demonstrated the utility of the enantioenriched allylic phosphates in late-stage N–H allylations of natural products and drug molecules and in cross-coupling reactions that occurred with excellent enantiospecificity.

Electrochemistry-Enabled C-Heteroatom Bond Formation of Alkyl Germanes

M. D. Schoetz, K. Deckers, G. Singh, E. Ahrweiler, A. Hoeppner & F. Schoenebeck*

J. Am. Chem. Soc. 2024, ASAP (DOI: 10.1021/jacs.4c08008)

Because of their robustness and orthogonal reactivity features, alkyl germanes bear significant potential as functional handles for the construction of C(sp³ )-rich scaffolds, especially in the context of modular synthetic approaches. However, to date, only radical-based reactivity has been accessible from these functional handles, which limits the types of possible decorations. Here, the authors describe the first general C(sp³ )–heteroatom bond formation of alkyl germanes (−GeEt₃) by leveraging electrochemistry to unlock polar reactivity. This approach allowed us to couple C(sp³ )–GeEt₃ with a variety of nucleophiles to construct ethers, esters, amines, amides, sulfonamides, sulfides, as well as C–P, C–F, and C–C bonds. The compatibility of the electrochemical approach with a modular synthetic strategy of a C1 motif was also showcased, involving the sequential functionalization of Cl, Bpin, and ultimately GeEt₃ via electrochemistry.

Manganese-Mediated Electrochemical Oxidation of Thioethers to Sulfoxides Using Water as the Source of Oxygen Atoms

M. A. Hoque,^† T. Jiang,^† D. L. Poole & S. S. Stahl*

J. Am. Chem. Soc. 2024, ASAP (DOI: 10.1021/jacs.4c07058)

Oxygen-atom transfer reactions are a prominent class of synthetic redox reactions that often use high-energy oxygen-atom donor reagents. Electrochemical methods can bypass these reagents by using water as the source of oxygen atoms through pathways involving direct or indirect (mediated) electrolysis. Here, manganese porphyrins and related mediators are shown to be effective molecular electrocatalysts for selective oxidation of thioethers to sulfoxides, without overoxidation to the sulfone. The reactions proceed by proton-coupled oxidation of a Mn^III –OH₂ species to generate a Mn^IV –OH and Mn^V ═O species. This methodology is compared to direct electrolysis methods initiated by single-electron oxidation of the thioether, and chloride-mediated electrochemical oxidation of thioethers. The Mn-mediated reactions operate at lower applied potential and exhibit improved substrate scope and functional group compatibility relative to direct electrolysis, and the tunability of the Mn-based mediators allows for improved performance relative to chloride-mediated electrolysis. An electrochemical parallel screening platform is developed and applied to a library of pharmaceutically relevant thioethers.

Late-Stage C(sp²)–C(sp³) Diversification via Nickel Oxidative Addition Complexes

C. Odena,^† T. G. Santiago,^† M. L. Linares,^† N. Castellanos-Blanco, R. T. McGuire, B. Chaves-Arquero, J. M. Alonso, A. Diéguez-Vázquez, E. Tan, J. Alcázar, P. Buijnsters, S. Cañellas* & R. Martin*

J. Am. Chem. Soc. 2024, ASAP (DOI: 10.1021/jacs.4c08404)

The authors describe nickel oxidative addition complexes (Ni-OACs) of drug-like molecules as a platform to rapidly generate lead candidates with enhanced C(sp³ ) fraction. The potential of Ni-OACs to access new chemical space has been assessed not only in C(sp² )–C(sp³ ) couplings but also in additional bond formations without recourse to specialized ligands and with improved generality when compared to Ni-catalyzed reactions. The development of an automated diversification process further illustrates the robustness of Ni-OACs, thus offering a new gateway to expedite the design–make–test–analyze (DMTA) cycle in drug discovery.

Angewandte Chemie International Edition

Synthesis of 1-Azabicyclo[2.1.1]hexanes via Formal Single Electron Reduction of Azabicyclo[1.1.0]butanes Under Photochemical Conditions

M. Zanini, A. Noble* & V. K. Aggarwal*

Angew. Chem. Int. Ed. 2024, Accepted (DOI: 10.1002/anie.202410207) 🔓

C(sp³ )-rich heterocycles are privileged building blocks for pharmaceuticals and agrochemicals. Therefore, synthetic methods that provide access to novel saturated nitrogen-containing heterocycles are in high demand. Herein, the authors report a general synthesis of 1-azabicyclo[2.1.1]hexanes (1-aza-BCH) via a formal cycloaddition of azabicyclo[1.1.0]butanes (ABB) with styrenes under photochemical conditions. To overcome the challenging direct single electron reduction of ABBs, a polar-radical-polar relay strategy was designed that leverages a fast acid-mediated ring-opening of ABBs to form bromoazetidines, which undergo efficient debrominative radical formation to initiate the cycloaddition reaction. The reaction is applicable to a broad range of ABB-ketones and the 1-aza-BCH products can be further functionalised to access larger saturated, conformationally rigid heterocycles.

Modular Synthesis of Heterobenzylic Amines via Carbonyl Azinylative Amination

A. A. Rafaniello,^† R. Kumar,^† R. C. Phillips & M. J. Gaunt*

Angew. Chem. Int. Ed. 2024, Accepted (DOI: 10.1002/anie.202408287) 🔓

Transformations enabling the synthesis of α-alkyl, α’-2-azinyl amines by addition of 2-heteroaryl-based nucleophiles to in situ-generated and non-activated alkyl-substituted iminium ions are extremely rare. Approaches involving classical 2-azinyl organometallics, such as the corresponding Grignard reagents, often fail to produce the desired products. Here, the authors report an operationally straightforward solution to this problem through the development of a multicomponent coupling process wherein a soft 2-azinyl indium nucleophile, generated in situ from the corresponding 2-iodo heteroarene and indium powder, adds to an iminium ion that is also formed directly in the reaction. This modular carbonyl azinylative amination (CAzA) displays a broad scope and only a metal reductant is needed to generate a reactive 2-azinyl nucleophile. Beyond the addition to iminium ions, the 2-azinyl addition to polyfluoromethyl ketones forms the corresponding tertiary alcohols.

ChemRxiv

Reductive Amination of Carbonyl C–C Bonds Enables Formal Nitrogen Insertion

C. Amber, L. T. Göttemann,^‡ R. T. Steele,^‡ T. M. Petitjean & R. Sarpong*

ChemRxiv 2024 (DOI: 10.26434/chemrxiv-2024-z8lw3) 🔓

Given its ubiquity in various biological and physical processes, the reductive amination of ketones and aldehydes is one of the oldest and most widely used methods for amine synthesis. As a cornerstone of synthetic chemistry, it has largely remained unchanged since its discovery over a century ago. Herein, the authors report the mechanistically-driven development of a complementary reaction, which reductively aminates the C–C σ-bond attached to carbonyls, not the carbonyl C–O π-bond, generating value-added linear and cyclic 3° amines in a modular fashion. Critical to the success of this endeavor were mechanistic insights that enabled the authors to modulate the resting state of a borane catalyst, minimize deleterious disproportionation of a hydroxylamine nitrogen source, and control the migratory selectivity of a key nitrenoid reactive intermediate. Experimental evidence support the reaction occurring through a reductive amination/stepwise reductive Stieglitz cascade, via a ketonitrone, which can be interrupted under catalyst-control to generate valuable N,N-disubstituted hydroxylamines. The method reported herein enables various net transformations that would otherwise require lengthy synthetic sequences using pre-existing technologies. This is highlighted by its application to a two-step protocol for the formal insertion of a single nitrogen atom into the core framework of abundant hydrocarbon feedstocks, the site-selective late-stage C–C amination of complex molecules, diversity-oriented synthesis of isomeric amines from a single precursor, and transposition of nitrogen to different positions within a heterocycle.

Photoredox Autocatalysis: Towards a Library of Generally Applicable Reductive Photocatalysts

J. Kaur,^† M. J. P. Mandigma,^† N. Bapat & J. P. Barham*

ChemRxiv 2024 (DOI: 10.26434/chemrxiv-2024-16879) 🔓

Dichotomous thinking dominates the field of synthetic photochemistry – either a reaction needs a photocatalyst or not. Herein, the authors report the discovery of photoredox autocatalytic pathway, a third mechanistic paradigm that is thus far overlooked, to access cyclic biaryl sulfonamides (BASNs). This reaction does not require exogenous catalyst as the visible light absorbing deprotonated product itself, with potent excited state reductive power, acts as the photocatalyst for its own synthesis. This finding implicated BASN as a novel organophotocatalyst architecture and allowed a rapid, modular, and low-cost combinatorial synthesis of a BASN library that expediated optimal photocatalyst screening. Furthermore, BASN was revealed as a general organophotocatalyst for a diverse set of transition metal-free transformations such as: intramolecular (spiro)-cyclizations, defunctionalizations, and C-C / C-heteroatom couplings.

Non-Canonical Tryptophan Synthesis Enabled by Larock Umpolung

J. Z. Huang, V. Y. Ying & M. R. Seyedsayamdost*

ChemRxiv 2024 (DOI: 10.26434/chemrxiv-2024-7bgzg) 🔓

Tryptophan plays a critical role in diverse natural products, biological processes, and pharmaceutical molecules. Facile access to this amino acid and its analogues from readily available building blocks, however, remains a long-standing challenge. Here, the authors report a regioselective synthesis of tryptophan and unnatural variants bearing C4-C7 substituents via Rh-catalyzed annulation between structurally diverse tert-butyloxycarbonyl (Boc) protected anilines and a serine derived alkynyl chloride. This transformation features C-H activation directed by a weakly coordinating Boc group, the umpolung reactivity of alkynyl chloride, and acetic acid-mediated reverse C-H rhodation to afford the C2 unsubstituted indole products in a redox-neutral fashion. The wide utility of this chemistry is demonstrated for the synthesis of halogenated, borylated, and poly-oxygenated tryptophans, drug analogues, dipeptides with crosslinks on tryptophan, and heterocycle-containing tryptophan derivatives.

Synthesis of Aryl-Fused Bicyclo[3.1.1]heptanes (BCHeps) and Validation as Naphthyl Bioisosteres

A. Kerckhoffs, M. Tregear, P. Hernández-Lladó, M. Runfola, H. Shearsmith, N. Frank, S. E. Squire, L. Moir, K. E. Christensen, F. Duarte, K. E. Davies & A. J. Russell*

ChemRxiv 2024 (DOI: 10.26434/chemrxiv-2024-t0t94) 🔓

While naphthalene rings are often encountered in drugs, candidates and lead molecules, they can be susceptible to cytochrome P450-mediated metabolism in biological systems and exhibit flat, sp² -rich structures, limiting their utility in drug-like candidates. Herein, the authors report the first library of derivatisable aryl-fused Bicyclo[3.1.1]heptanes (BCHeps) as bioisosteric replacements for (β-)naphthalene and other fused bicyclic aromatics. They incorporate the BCHep-based naphthyl isosteres into the AhR antagonist ezutromid and observe geometrically similar exit vectors while reducing Fsp² , and retainment of biological activity while improving metabolic stability towards CYP metabolism, validating these motifs as ‘true’ bioisosteric replacements for meta-substituted arenes and 2-naphthalenes.

Organic Process Research & Development

Analysis of the Change in Molecular Complexity of Reaction Products in Process Development Activities at AstraZeneca Over Time

G. Karageorgis,* J. J. Douglas & G. P. Howell

Org. Process Res. Dev. 2024, ASAP (DOI: 10.1021/acs.oprd.4c00224)

The assessment of molecular complexity of active pharmaceutical ingredients (APIs) can help guide decisions within drug development, for example, by correlation to sustainability targets, project resource requirements, and predicted development and manufacturing timelines. However, such quantifications are limited by the challenge of defining complexity itself as well as the small sample size of API molecules making longer term comparisons challenging. The authors have used four complementary approaches to calculate the complexity of reaction products of more than 165,000 reaction entries across their process development electronic laboratory notebooks. Importantly, this dataset covers both intermediates, APIs, and other molecules requiring synthesis, thus, attempts to provide an analysis of reaction products from all their synthetic chemistry activities. This information facilitated the investigation of changes in the mean values of different measures of molecular complexity per year between 2007 and 2020.

Fit-for-Purpose Synthesis of a KRAS^G12C Covalent Inhibitor, via a Diastereoselective Hayashi Arylation

C. Molinaro,* N. Wong, N. A. White, L. E. Sirois, R. Bigler, Q. P. Bindschaedler, S. Do, S. Malhotra & F. Gosselin

Org. Process Res. Dev. 2024, ASAP (DOI: 10.1021/acs.oprd.4c00211)

An enabling, fit-for-purpose synthesis of stereochemically pure KRAS^G12C covalent inhibitor 1, a potential new treatment for cancer, is described. The synthetic route provided 1 in 13 steps from commercially available 2-fluoro-5-methylaniline (2), tert-butyl (S)-3-methylpiperazine-1-carboxylate (8) and (S)-(1-methylpyrrolidin-2-yl)methanol (10). A key transformation in this sequence was the diastereoselective 1,4-addition of an aryl boronate derived from 2 with rac-4-methylcyclohex-2-en-1-one (rac-4) in a Hayashi arylation that sets two relative stereocenters of the target molecule. This in turn inspired the development of an improved synthesis of (R)-4-methylcyclohex-2-en-1-one ((R)-4) via optimized methodology for the asymmetric monohydrogenation of 1,4-dienes, thus setting the stage for a fully asymmetric synthesis of inhibitor 1.

Organic Letters

Systematic Route to Construct the 5–5–6 Tricyclic Core of Furanobutenolide-Derived Cembranoids and Norcembranoids

M. Chan, N. J. Hafeman, T. J. Fulton & B. M. Stoltz*

Org. Lett. 2024, ASAP (DOI: 10.1021/acs.orglett.4c01820) 🔓

The authors present a highly efficient method for constructing the intricate 5–5–6 fused ring system commonly found in the polycyclic furanobutenolide-derived cembranoid and norcembranoid natural product family with remarkable diastereoselectivity, utilizing an intramolecular Diels–Alder reaction as the cornerstone. Notably, employing a propargyl ether tether as the dienophile yields significant enhancements in the transformation process compared to its propargyl ester counterpart, as demonstrated in their previous total synthesis of havellockate. This advancement holds promising implications for future investigations, offering a streamlined pathway for rapidly assembling the tricyclic core characteristic of this diverse family of natural products.

That’s all for this issue! Have a great week and we’ll see you next Monday.