About

Scott E. Schaus is a Professor of Organic and Medicinal Chemistry at Boston University. His research focuses on enantioselective catalytic synthetic methodologies for chemical synthesis and biomedical research, conducted at the Boston University Center for Molecular Discovery. His work includes developing catalytic methods such as enantioselective boronate reactions, asymmetric Mannich reactions, and metal-promoted condensation reactions. These methodologies are aimed at constructing chiral building blocks and natural products, utilizing boronates and catalysis with cinchona amine, acid, and diol catalysts. In addition to his contributions to synthetic chemistry, Professor Schaus is engaged in biomedical research aimed at advancing translational science in the treatment of cancer and infectious diseases. His collaborative efforts include developing treatments for challenging cancers, such as liver cancer, in partnership with other faculty and clinicians, as well as working against neglected tropical diseases. His research is conducted in conjunction with the NIH-funded Center for Molecular Discovery at Boston University. Since 2001, he has mentored graduate students and postdoctoral fellows, many of whom have pursued careers in academia and the pharmaceutical industry.

Research topics

• Computer Science
• Biology
• Cell biology
• Materials science
• Genetics
• Nanotechnology
• Process engineering
• Systems engineering
• Business
• Engineering
• Chemistry
• Risk analysis (engineering)
• Cancer research
• Biochemistry
• Biochemical engineering
• Medicine

Selected publications

• Advantages of Flow Chemistry in the Electrochemical Tri‐ and Difluoromethylation of Purines and Pyrimidines

  Advanced Synthesis & Catalysis · 2026-02-20

  articleSenior authorCorresponding

  Trifluoromethyl (–CF 3 ) and difluoromethyl (–CF 2 H) substituents are key structural motifs in modern pharmaceuticals due to their ability to enhance lipophilicity, metabolic stability, and introduce unique electronic properties. Here, we report a sustainable and operationally facile electrochemical method to introduce these groups directly onto purine and pyrimidine scaffolds, heterocycles central to nucleobase chemistry and drug design, without the need for stoichiometric oxidants, transition‐metal catalysts, or photocatalysts. Using commercially available sodium trifluoromethanesulfinate and sodium difluoromethanesulfinate under mild conditions in an undivided IKA ElectraSyn 2.0 cell, the reaction proceeds efficiently across more than 15 substrates, affording up to 80% yield. The difluoromethylation process was further translated into a microflow electrolysis platform from Analytical Sales & Services, enhancing scalability and throughput with an average 1.5‐fold increase in product generation rate relative to batch. This process is the first demonstration of electrochemical difluoromethylation of heterocycles in flow and establishes a versatile, green synthetic platform for accessing fluorinated nucleobase derivatives and other bioactive small molecules.

  PublisherDOI

• Competition Between Enzymatic and Anodic Oxidation in Electro-chemical Galactose Oxidase Catalysis

  ChemRxiv · 2026-01-07

  article1st authorCorresponding

  Electrochemical activation of galactose oxidase (GalOx) has emerged as a sustainable alternative to peroxide-driven systems for aerobic alcohol oxidation. Here, we present a systematic investigation of wild-type GalOx under electrochemical conditions for the oxidation of non-carbohydrate primary alcohols. While benzylic substrates undergo selective enzyme-mediated oxidation to the corresponding alde-hydes, we identify a prominent competing pathway in which weakly bound substrates are directly oxidized at the electrode surface, fre-quently resulting in over-oxidation to carboxylic acids. Using 4-methoxybenzyl alcohol as a diagnostic probe, we disentangle the enzymat-ic and non-enzymatic pathways and demonstrate that both applied potential and electrode material exert decisive control over product selectivity. In contrast, aryl 1,2-diols are oxidized exclusively through a direct anodic mechanism, completely bypassing enzymatic turno-ver. Collectively, these results define critical operational boundaries for electro-enzymatic GalOx catalysis and underscore the necessity of rigorous enzyme-free controls in the development of selective electrochemical biocatalytic oxidation platforms.

  PublisherDOI

• Preclinical Lead Optimization of Small Molecule Inhibitors of TFCP2 (LSF) for the Treatment of Liver Cancer

  Journal of Medicinal Chemistry · 2025-12-18

  articleSenior authorCorresponding

  Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality, underscoring the need for new therapeutic strategies. Screening a library of dihydroquinolinones, termed Factor Quinolinone Inhibitors (FQIs), identified compound 1 as a potent in vitro inhibitor of the oncogenic transcription factor LSF/TFCP2 and as an in vivo suppressor of HCC tumor growth without observable cytotoxicity. Unfortunately, 1 had limited bioavailability. In this report, we detail the identification and optimization of the structure–activity relationships (SAR) of chiral and achiral FQI analogs. The SAR study led to the discovery of achiral 12 (FQI2–34), a highly potent, selective compound with desirable absorption, distribution, metabolism, and excretion (ADME) properties and potent in vivo antitumor activity. We also demonstrated that FQIs directly bind to TFCP2 with affinities in the nanomolar ranges. Our results suggest that FQIs are promising chemotherapeutics for TFCP2-driven cancer, especially HCC.

  PublisherDOI

• Chiral Amino Alcohols via Catalytic Enantioselective Petasis Borono–Mannich Reactions

  The Journal of Organic Chemistry · 2025-08-18

  articleSenior authorCorresponding

  Chiral amino alcohols are valuable building blocks in the synthesis of drugs, natural products, and chiral ligands used in enantioselective catalysis. The Petasis borono-Mannich reaction is a multicomponent condensation reaction of aldehydes, amines, and boronic acids to afford chiral amines. This report describes a practical, easily scaled, enantioselective Petasis borono-Mannich reaction of glycolaldehyde with primary or secondary amines and boronates catalyzed by BINOL-derived catalysts to afford chiral 1,2-amino alcohols in high yields and enantioselectivities. The reactions are executed at room temperature in ethanol or trifluorotoluene using commercially available reagents and leverage an inherently attractive feature of the multicomponent reaction: the ability to use amines and boronates that possess a wide range of structural and electronic properties. Computational modeling of the diastereomeric transition states using DFT calculations identified a nonconventional CH···O interaction and CH-π as key features that selectively stabilize the transition state, leading to the major enantiomer. The enantioselective catalytic reaction exemplifies a truly practical multicomponent condensation to afford 1,2-amino alcohols in a highly enantioenriched form.

  PublisherDOI

• Galactose Oxidase‐Catalyzed Benchtop and Electrochemical Oxidation of C1‐Alkylated <i>β</i>‐D‐Galactopyranoside Derivatives

  European Journal of Organic Chemistry · 2025-08-06

  articleSenior authorCorresponding

  The reaction conditions of wild‐type galactose oxidase (GalOx)‐catalyzed oxidation of C‐1 alkylated β ‐D‐galactopyranoside derivatives are established and optimized. The benchtop oxidation reaction uses a three‐enzyme system comprising GalOx, catalase, and horseradish peroxidase (HRP). Under the optimized conditions, methyl‐ β ‐D‐galactopyranoside achieves 86% conversion after 24 h of reaction at room temperature. No previous study has investigated how the C‐1 position of β ‐D‐galactopyranoside derivatives influences GalOx–substrate interactions. To address this, a panel of C‐1 alkylated β ‐D‐galactopyranoside derivatives is synthesized and tested for the first time. The results show that although GalOx tolerates modifications at the C‐1 position, the size, shape, and electronic properties of the substituent significantly affect catalytic efficiency. The same β ‐D‐galactopyranoside derivatives are also investigated on an electrochemical setup, which replaces the HRP activator with electrochemical activation. The electrochemical activation method achieves comparable conversion and preserves substrate specificity, offering a promising and cost‐effective alternative to traditional enzymatic setups. This work provides a foundation for understanding C‐1 structural tolerance in GalOx–substrate interactions and demonstrates electrochemical activation as a promising and practical alternative to traditional enzymatic activation.

  PublisherDOI

• Strategy, Design, and Fabrication of Electrochemical Biosensors: A Tutorial

  ACS Sensors · 2024 · 91 citations

  • Computer Science
  • Computer Science
  • Risk analysis (engineering)

  Advanced healthcare requires novel technologies capable of real-time sensing to monitor acute and long-term health. The challenge relies on converting a real-time quantitative biological and chemical signal into a desired measurable output. Given the success in detecting glucose and the commercialization of glucometers, electrochemical biosensors continue to be a mainstay of academic and industrial research activities. Despite the wealth of literature on electrochemical biosensors, reports are often specific to a particular application (e.g., pathogens, cancer markers, glucose, etc.), and most fail to convey the underlying strategy and design, and if it is transferable to detection of a different analyte. Here we present a tutorial review for those entering this research area that summarizes the basic electrochemical techniques utilized as well as discusses the designs and optimization strategies employed to improve sensitivity and maximize signal output.

  PublisherDOI

• Discovery of pyrazolopyrrolidinones as potent, broad-spectrum inhibitors of Leishmania infection

  Frontiers in Tropical Diseases · 2023-01-17 · 8 citations

  articleOpen accessSenior authorCorresponding

  Introduction Leishmaniasis is a parasitic disease that affects more than 1 million people worldwide annually, predominantly in resource-limited settings. The challenge in compound development is to exhibit potent activity against the intracellular stage of the parasite (the stage present in the mammalian host) without harming the infected host cells. We have identified a compound series (pyrazolopyrrolidinones) active against the intracellular parasites of Leishmania donovani and L. major; the causative agents of visceral and cutaneous leishmaniasis in the Old World, respectively. Methods In this study, we performed medicinal chemistry on a newly-discovered antileishmanial chemotype, with over 100 analogs tested. Studies included assessments of antileishmanial potency, toxicity towards host cells, and in vitro ADME screening of key drug properties. Results and discussion Members of the series showed high potency against the deadliest form, visceral leishmaniasis (approximate EC 50 ≥ 0.01 µM without harming the host macrophage up to 10.0 µM). In comparison, the most efficient monotherapy treatment for visceral leishmaniasis is amphotericin B, which presents similar activity in the same assay (EC 50 = 0.2 µM) while being cytotoxic to the host cell at 5.0 µM. Continued development of this compound series with the Discovery Partnership with Academia (DPAc) program at the GlaxoSmithKline Diseases of the Developing World (GSK DDW) laboratories found that the compounds passed all of GSK’s criteria to be defined as a potential lead drug series for leishmaniasis. Conclusion Here, we describe preliminary structure-activity relationships for antileishmanial pyrazolopyrrolidinones, and our progress towards the identification of candidates for future in vivo assays in models of visceral and cutaneous leishmaniasis.

  PublisherOA PDFDOI

• Identification of Small Molecules with Improved Potency against Orthopoxviruses from Vaccinia to Smallpox

  Antimicrobial Agents and Chemotherapy · 2022-10-12 · 9 citations

  articleOpen access

  The genus Orthopoxvirus contains several human pathogens, including vaccinia, monkeypox, cowpox, and variola virus, the causative agent of smallpox. Although there are a few effective vaccines, widespread prophylactic vaccination has ceased and is unlikely to resume, making therapeutics increasingly important to treat poxvirus disease. Here, we described efforts to improve the potency of the anti-poxvirus small molecule CMLDBU6128. This class of small molecules, referred to as pyridopyrimidinones (PDPMs), showed a wide range of biological activities. Through the synthesis and testing of several exploratory chemical libraries based on this molecule, we identified several compounds that had increased potency from the micromolar into the nanomolar range. Two compounds, designated (12) and (16), showed inhibitory concentrations of 326 nM and 101 nM, respectively, which was more than a 10-fold increase in potency to CMLDBU6128 with an inhibitory concentration of around 6 μM. We also expanded our investigation of the breadth of action of these molecules and showed that they can inhibit the replication of variola virus, a related orthopoxvirus. Together, these findings highlighted the promise of this new class of antipoxviral agents as broad-spectrum small molecules with significant potential to be developed as antiviral therapy. This would add a small molecule option for therapy of spreading diseases, including monkeypox and cowpox viruses, that would also be expected to have efficacy against smallpox.

  PublisherOA PDFDOI

• Pharmacologic Manipulation of Late SV40 Factor Suppresses Wnt Signaling and Inhibits Growth of Allogeneic and Syngeneic Colon Cancer Xenografts

  American Journal Of Pathology · 2022-06-13 · 3 citations

  articleOpen access
  PublisherOA PDFDOI

• Small molecules targeting Leishmania Braziliensis: potential targets for chemotherapy

  Arca - Repositório Institucional da Fiocruz · 2022-01-01

  otherOpen access

  Cutaneous Leishmaniasis (CL) caused by L. braziliensis presents as several clinical forms, which range from a localized ulcerated lesion to disfiguring lesions in mucosal areas. L. braziliensis can also cause disseminated leishmaniasis, a severe form of disease that frequently presents with mucosal involvement. CL affects 1.5 million people worldwide, and the current first line treatment are pentavalent antimony compounds that present toxicity and are subject to parasite resistance, making it evident the need for better therapeutical options. One of the challenges in the development of novel antileishmanial compounds is achieving potent activity against the intracellular stage of the parasite, the stage present in the mammalian host, without harming the host cell. Previously, we identified a compound series that displayed effective antiparasitic activity against L. braziliensis. Herein, we explored these compounds and evaluated their effectiveness employing murine macrophages, followed up by experiments in vivo. Macrophages infected with L. braziliensis and exposed to the compound series in a dose dependent manner showed that molecules Cpd1 and Cpd2 reduced the percentage of infected cells and the number of intracellular amastigotes in a significant manner. Similar results were obtained upon infection with L. major and both compounds also did not exhibit cellular toxicity. Parasite killing was accompanied by an increase in the production of TNF and superoxide and both molecules are associated macrophage effector functions. Lastly, in a pre-clinical mouse model of CL caused by L. braziliensis, we observed that topical application of Cpd1, in gel- based form employing bacterial cellulose, impaired lesion development and significantly reduced parasite burden. These results indicate that this compound series can be further explored for the development of novel chemotherapeutic alternatives for CL caused by L. braziliensis, the causative agent of localized, mucosal and disseminated leishmaniasis.

  Publisher

Recent grants

• Advancement of a poxvirus antiviral

  NIH · $5.8M · 2020–2029

• NIH Grant P41GM086180

  NIH · $231k · 2011

• CAREER: Interdisciplinary Research in Organic Synthesis and Biology

  NSF · $640k · 2004–2008

• Library Synthesis Core

  NIH · $35.0M · 2014

• Enantioselective Catalytic Boronate Reactions

  NIH · $2.9M · 2007–2019

Frequent coauthors

• J. A. Westbrook

  61 shared

• John A. Porco

  36 shared

• Eric N. Jacobsen

  Harvard University Press

  26 shared

• Sha Lou

  Tongji University

  23 shared

• Philip N. Moquist

  Pfizer (United States)

  23 shared

• Jennifer M. Goss

  Boston University

  21 shared

• Hang Gyeong Chin

  New England Biolabs (United States)

  20 shared

• Yi Luan

  University of Science and Technology Beijing

  20 shared