About

The Renata group at Rice University is an interdisciplinary research team led by Professor Hans Renata. Their work focuses on the interface of organic synthesis, enzymology, and natural product chemical biology. The group aims to integrate these fields to advance understanding and innovation in chemical biology through the study and application of enzymatic processes and organic synthesis techniques.

Research topics

• Combinatorial chemistry
• Chemistry
• Organic chemistry
• Computer Science
• Stereochemistry
• Nanotechnology
• Materials science
• Biochemical engineering
• Programming language
• Engineering
• Biochemistry

Selected publications

• Total Synthesis of Allocyclinone A via Late‐Stage Halogen Swapping

  Angewandte Chemie · 2026-05-14

  articleSenior author

  ABSTRACT Allocyclinones A–D are small congeners of angucyclinones with several unusual structural features and potent antibiotic activity against various Gram‐positive pathogens. Allocyclinone A, the most active congener, contains an intriguing aromatic trichloromethyl substituent that has never been observed in other natural products before. In this study, we report a modular total synthesis of allocyclinones A and B featuring the convergent assembly of three key building blocks through Hauser annulation and cross‐couplings. The synthesis of allocyclinone A was made possible by the application of a late‐stage trifluoromethyl‐to‐trichloromethyl swap, providing a potentially generalizable strategy for aromatic trichloromethyl installation in complex settings. The antibiotic activity of the scaffold was also verified, and attempts to elucidate its mode of action were performed.

  PublisherDOI

• CCDC 2478468: Experimental Crystal Structure Determination

  The Cambridge Structural Database · 2026-03-17

  datasetOpen access

  An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  PublisherDOI

• A Diversity-Oriented Chemoenzymatic Platform for the Synthesis of Indolactam Natural Products and Analogues Thereof

  ChemRxiv · 2026-05-11

  articleOpen accessSenior author

  Isolated from Streptomyces and other bacterial genera, the indolactams comprise a large family of indole alkaloids bearing a characteristic nine-membered macrolactam core. Early investigations revealed that several family members (e.g., indolactam V, lyngbyatoxin A, and teleocidin B) are potent modulators of protein kinases C (PKCs), a class of ubiquitous serine/threonine kinases that play critical roles in signaling cascades and myriad biological processes. Herein, we describe the development of a modular chemoenzymatic platform for the synthesis of indolactam natural products and derivatives thereof. By leveraging enzymes from teleocidin biosynthesis alongside traditional chemical transformations, we provide rapid and streamlined synthetic access to over twenty functionalized indolactams, lyngbyatoxins, and teleocidins. In particular, we demonstrate the synthetic utility of P450 TleB and prenyltransferase TleC for indole C–H amination and prenylation, respectively, to quickly construct and derivatize indolactam skeletons. Further use of methyltransferase- or Bronsted acid-mediated cyclization generates more complex family members, including teleocidin B-4 and several unnatural analogues thereof.

  PublisherOA PDFDOI

• Total Synthesis of Allocyclinone A via Late-Stage Halogen Swapping

  ChemRxiv · 2026-01-21

  articleOpen accessSenior author

  Supporting information for this article is given via a link at the end of the document.

  PublisherOA PDFDOI

• Early- and late-stage chemoenzymatic functionalisation of steroid-inspired compounds

  ChemRxiv · 2026-03-30

  articleOpen access

  Selective C-H functionalisation of small molecule leads is a powerful approach for efficient chemical space exploration and medicinal chemistry optimisation. Here, we report a screening platform for early- and late-stage chemoenzymatic oxidation of steroid-inspired compounds using a panel of P450 BM3 variants. Late-stage oxidation of sterol transport protein inhibitors and their intermediates revealed enzyme- and substrate-dependent regioselectivity, yielding hydroxylated analogues that provided rapid structure-activity relationship insights into the spirooxepinoindole as a privileged scaffold and its potential metabolic products. Early-stage functionalisation of steroidal building blocks, including the Wieland-Miescher ketone and acetyl- cis -decalone, furnished hydroxylated derivatives with high diastereoselectivity. Notably, both enantiomers of both diastereoisomers of the C6-hydroxylated Wieland-Miescher ketone were obtained in preparative quantities, enabling access to valuable early-stage building blocks. This work highlights the potential of chemoenzymatic approaches to deliver regio- and stereoselective oxidations of challenging steroid-like scaffolds, complementing classical synthetic methods and expanding opportunities in medicinal chemistry and natural product synthesis.

  PublisherOA PDFDOI

• Collective Synthesis of Diverse Onoceroids via Chelation-Assisted Radical Cross-Coupling

  ChemRxiv · 2026-03-20

  articleOpen accessSenior author

  Onoceroids are complex triterpenoids that arise through bidirectional cyclizations of squalene or its diepoxide derivative, followed by oxidative tailorings. By virtue of this biosynthetic sequence, many onoceroids possess unsymmetrical pseudodimeric structures, which present an unusual synthetic challenge. In this study, we describe a family-level solution to the synthesis of all known subtypes of onoceroid skeleton. A key feature in this study is the discovery of an important chelation effect that facilitates high cross-selectivity in radical C(sp 3)-C(sp 3) cross-coupling between two highly similar but distinct fragments. Combining this process with other modern radical reactions enables rapid access to more than 20 naturally occurring onoceroids. This study provides a blueprint for constructing sp 3-rich polycyclic architectures through the combination of modern synthetic paradigms.

  PublisherOA PDFDOI

• Total Synthesis of Allocyclinone A via Late‐Stage Halogen Swapping

  Angewandte Chemie International Edition · 2026-05-14

  articleSenior authorCorresponding

  Allocyclinones A-D are small congeners of angucyclinones with several unusual structural features and potent antibiotic activity against various Gram-positive pathogens. Allocyclinone A, the most active congener, contains an intriguing aromatic trichloromethyl substituent that has never been observed in other natural products before. In this study, we report a modular total synthesis of allocyclinones A and B featuring the convergent assembly of three key building blocks through Hauser annulation and cross-couplings. The synthesis of allocyclinone A was made possible by the application of a late-stage trifluoromethyl-to-trichloromethyl swap, providing a potentially generalizable strategy for aromatic trichloromethyl installation in complex settings. The antibiotic activity of the scaffold was also verified, and attempts to elucidate its mode of action were performed.

  PublisherDOI

• Development of a Diastereoselective Csp²–Csp³ Cross-Coupling Reaction Inspired by Macrocyclic RiPP Natural Products

  Organic Letters · 2025-07-09 · 3 citations

  articleOpen accessCorresponding

  ) side chain cross-links are a rapidly growing subclass of ribosomally synthesized and post-translationally modified peptides (RiPPs), with significant potential in the development of new pharmaceuticals. This report presents a method for the efficient synthesis of derivatives of this class using a diastereoselective cross-electrophile coupling for the formation of the key β-aryl-alkyl cross-link.

  PublisherDOI

• Concise Synthesis of Fostriecin and Analogs through Late-Stage Chemoenzymatic Installation of Their Key Pharmacophores

  Journal of the American Chemical Society · 2025-07-09 · 3 citations

  articleOpen accessSenior authorCorresponding

  As one of the most potent and selective protein phosphatase inhibitors, fostriecin shows a broad range of anticancer activities. In light of this property, a phase I clinical trial was conducted on fostriecin but was soon halted due to issues with compound stability and purity. Numerous efforts in the past two decades have yielded 17 successful syntheses that proceed in 17–34 steps. Herein, we develop a modular chemoenzymatic approach that provides fostriecin and its analogs in a collective manner in 9 steps (longest linear sequence) from readily available (R)-1,2,4-butanetriol. The synthesis features a convergent assembly of three key fragments and a late-stage chemoenzymatic derivatization of an advanced intermediate that (i) installs two of the key pharmacophores and (ii) allows ready diversification of the hydrophobic tail. A key feature in this derivatization is the optimization of an enzymatic C–H oxidation step through the concurrent use of rational enzyme engineering and small molecule additives for activity improvement. Cumulatively, our strategy capitalizes on the exquisite chemoselectivity of enzymatic transformations while ensuring synthetic modularity and versatility for analog generation. This work will facilitate future investigations into the biological activities and medicinal chemistry of the natural product family.

  PublisherOA PDFDOI

• Harnessing a Ketone-Accepting Pictet-Spenglerase for the Asymmetric Construction of 1,1-Disubstituted Tetrahydro-ß-Carboline Alkaloids

  ChemRxiv · 2025-01-27 · 1 citations

  preprintOpen accessSenior author

  In light of the ubiquity of 1,1’-disubstituted tetrahydro-ß-carboline (THBC) motif in alkaloid natural products, developing asymmetric methodology for its preparation is highly valuable. Despite the immense progress towards achieving stereoselective Pictet-Spengler reaction with aldehydes, the analogous reaction with ketones is still underdeveloped. Exploiting KslB, a Pictet-Spenglerase from the biosynthesis of kitasetaline, we develop a general, diastereoselective, and protecting-group free method for the construction of densely functionalized THBCs with α-quaternary center by coupling tryptophan derivatives and α-keto acids. We determine the stereochemistry of kitasetalic acid, KslB’s physiological product and a key biosynthetic intermediate towards kitasetaline, and established that KslB’s selectivity is opposite to what is achieved chemically. Our investigations of KslB show its high activity (TTN>438,000), substrate promiscuity, and tolerance for high substrate concentrations (0.1M). Additionally, a TrpB-KslB cascade enables the construction of complex tricyclic products from simple indoles in one-pot. X-ray structural characterization of KslB sheds light on potential active site interactions to account for its stereoselectivity and ability to accept ketone substrates.

  PublisherOA PDFDOI

Recent grants

• Applications of Biocatalytic C–H Functionalization in Complex Molecule Synthesis

  NIH · $3.7M · 2018–2028

• CAREER: Chemoenzymatic Total Synthesis of Terpenoids via P450 Catalysis

  NSF · $670k · 2020–2022

Frequent coauthors

• Christian R. Zwick

  AbbVie (United States)

  26 shared

• Fuzhuo Li

  Fudan University

  24 shared

• Frances H. Arnold

  16 shared

• Phil S. Baran

  Scripps Research Institute

  13 shared

• Alexander Amatuni

  13 shared

• Z. Jane Wang

  13 shared

• Heping Deng

  Rice University

  13 shared

• Jian Li

  Shanghai Jiao Tong University

  12 shared