Knowledge Center

High Throughput Experimentation (HTE) has emerged as an important tool to assist and accelerate the productivity of the synthetic chemist. This iterative process of design, execution, data analysis, and hit identification enables rapid exploration of conditions for reaction discovery and optimization. In this article, we highlight the powerful use of HTE within the fields of multi-catalysis and new route synthesis, with a particular focus on late-stage functionalization.

Watch this webinar presented by Seqens team of experts to understand how you can benefit from early solid form screening and related activities.

Watch this webinar where our experts will present detailed case studies on the development of a continuous process to an API and on the development of safe processes to key pharmaceutical intermediates or specialty ingredients.

Watch this webinar where SEQENS will present how to help solving the specific manufacturing challenges associated with the New Molecular Entities in development in oncology.

In this article, we wish to highlight some recent developments for implementing more sustainable processes in the field of photochemistry, flow chemistry, and biocatalysis. Smarter process is also about process intensification and combining technologies, such as flow chemistry with photochemistry or biocatalysis.

In this study, we present an efficient and straightforward dearomative hydroalkylation of indoles. By utilizing alkanes or ethers as alkyl radical sources and employing TBADT as a costeffective photocatalyst for direct hydrogen atom transfers (HAT), we achieved successful conversion of these heterocyclic derivatives into 2-alkylindolines with good to excellent yields and high diastereoselectivity under mild reaction conditions.

Herein we describe a sustainable and efficient photocatalytic method for the stereoselective radical alkylation of chiral sulfinyl imines. By employing readily available non-prefunctionalized radical precursors and the cost-effective TBADT as a direct HAT photocatalyst, we successfully obtain diverse chiral amines with high yields and excellent diastereoselectivity under mild conditions.

The radical Truce–Smiles rearrangement is a straightforward strategy for incorporating aryl groups into organic molecules for which asymmetric processes remains rare. By employing a readily available and non-expensive chiral auxiliary, we developed a highly efficient asymmetric photocatalytic acyl and alkyl radical Truce–Smiles rearrangement of α-substituted acrylamides using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom–transfer photocatalyst , along with aldehydes or C-H containing precursors.

An enantioselective chiral phosphoric acid catalyzed formal [4+2] cycloaddition between 2-benzothiazolimines and N-H-1,3-dienecarbamates is described. A divergence in reaction pathways was observed depending on the dienes employed. The reaction performed with 4-substituted dienes produced benzothiazolopyrimidines as major product in yields ranging from 42 to 67%, as single diastereoisomer and with enantioselectivity between 93 and 99%.

We previously showed that the physiological concentration of 17β‑estradiol in the vaginal environment is sufficient to affect the membrane dynamics and adhesion phenotype of the Lactobacillus crispatus strain CIP104459. However, L. crispatus is a heterogeneous species. Here, we investigated the effect of 17β‑estradiol on the recently isolated L. crispatus vaginal strain V4, related to a cluster distant from CIP104459 and at the limit of being a different subspecies.

Lactobacilli and estrogens play essential roles in vaginal homeostasis. We investigated the potential direct effect of 17β-estradiol on a vaginal strain of Lactobacillus crispatus, the major bacterial species of the vaginal microbiota.

Chiral cyclobutanes are important structural features that are widely present in many biologically active natural and non-natural products. The threedimensional structure of cyclobutanes opens opportunities for applications in medicinal chemistry, and the introduction of this structural motif in smallmolecule drug candidates has been increasing in recent years.

From a process chemist point of view, developing an enzymatic process at industrial scale, is very much the same challenges and principles than any other chemical processes strategies. The exception relies however in understanding the behaviour of the biocatalyst for optimal performance and robustness. In this article, we wish to review the key stages that are required for implementing a biocatalytic process at industrial scale, supported by 4 case studies.

We asked 9 questions to Dr. Julien Leroudier, our technical expert in solid state characterization and scalable crystallization process about solid form.

Over the past decade, a profound shift has been underway in the pharmaceutical industry, as continuous flow processes gain momentum alongside traditional batch methods. This transformation is propelled by advancements in flow reactor technology, promising enhanced efficiency, safety, and sustainability in chemical production. In this article, we delve into the transformative power of flow chemistry, exploring its myriad benefits and applications in fine chemicals and active pharmaceutical ingredient (API) manufacturing.

Seqens has developed a unique FOS composition, made from sucrose and presenting a large diversity in chain length. While short chains are metabolized quickly by colonic bacteria, medium chains have a sustained effect over time and very long chains are likely to be excreted before being fully metabolized by the bacteria.  Our unique FOS composition corresponds to an optimal balance between short and medium chain lengths. 

We asked 5 questions to Dr. Sonia Lombardo, Preformulation Solid State Engineer at SEQENS, about bioavailability improvement and pre-formulation studies during drug development.

The latest generations of peptides, obtained via disruptive technologies such as synthetic biology and artificial intelligence, mark a break with conventional chemistry that is modernizing their image.

Watch this webinar where SEQENS and GenEvolutioN will present how to cope with the new Nitrosamines regulations for the development of Drug Substances and Drug Products.

Facing a highly competitive global market with increasing awareness on environmental issues, chemical production is making its way toward a paradigm shift to more efficient, more environmentally friendly, and more versatile manufacturing processes. In this white paper, we wish to review some of the key advanced tools available to process chemists for addressing the challenges in process intensification.

Among the different fields of chemical approaches available to the synthetic chemists, biocatalysis is only being slowly adopted, especially due to a lack of know-how and practical experience. However,enzymatic catalysis is a mature technology, and this should encourage more chemists to take further ownership and expand applications in modern chemistry.

The access to a novel variety of 4-fluorinated isoxazoles bearing an aryl or alkyl group at the C-3 position and an acetal fragment at the C-5 position has been achieved through a direct fluorination using N-fluorobenzenesulfonimide (NFSI) with yields up to 75%. This method was transposed to gram-scale and has been applied to the formal synthesis of a bioactive compound that increases CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) activity.

During this webinar, we present the specific challenges encountered by Biotech companies when developing New Chemical Entities from Discovery phase to Early Clinical phases. A case study is presented on an API presenting a low water solubility and at the same time a low solubility in lipophilic solvents.

Discover in the latest Organic Letters issue, how SEQENS in collaboration with Géraldine Masson, have developed a more greener approach for the decarboxylative borylation, leading efficiently to a- and b-amino-boronamides, an important class of compounds in medicinal chemistry.

This paper presents the different strategies considered to enhance pharmaceutical drugs bioavailability.
A special focus is made on the need
to understand, at early stage, the behaviour and the characteristics of these compounds, especially physical, chemical and biological
properties.

Highly potent drugs represent a growing proportion of medicines, including therapies in development and those commercially available. In this article, discover some best practices and synthetic route considerations for delivering highly potent drugs.

The concept of multi-catalysis is an emerging field targeting the development of new efficient catalytic systems combining multi-step synthesis in new ‘one-pot’ transformations or in multi-catalytic sequences.

Seqens Personal Care Article

Nitrosamines are a group of organic compounds containing the nitroso functional group. In this white paper, we review the main analytical techniques that have been investigated, and then we will present our work regarding the development of a UPLC-HRMS technique for identifying and quantifying Nitroso Drug Substances Related Impurities, at ppb level in APIs.

The catalytic properties of Seqenzym FT, a fungal fructosyltransferase heterologously
expressed in yeasts, were investigated at a temperature of 55 C and pH 5.5. The initial rate measurements showed that the transfructosylation rate was only slightly inhibited by sucrose above the
concentration of 1.5 M. Compared to other commercial preparations, Seqenzym FT can better produce FOS with a higher degree of polymerization.

About 30% of all APIs carry a Fluor atom, and many APIs need at least one fluorinated intermediate during their synthesis. Using continuous flow chemistry for fluorination steps could improve reactions performances in terms of reaction time and conversion ratio.

Enzyme evolution involves some changes of amino acid residues that constitute the sequence of the protein, which can alter its conformational dynamics and ultimately affect its enzymatic function

Seqens participated to this year’s annual meeting of the American Society of Clinical Oncology (ASCO), held in Chicago on June 2-6 .

A proof-of-concept study for the synthesis of 1,2-difluorobenzene from 2-fluoroaniline via the Balz−Schiemann reaction using HF/pyridine as the fluorinating reagent is reported. Key to success for a fast reaction, a clean reaction profile - and thus high product selectivity - was a photochemically induced fluorodediazoniation of the in situ-generated diazonium salt performed in a continuous flow mode.

We report the draft genome sequence of Lactobacillus crispatus CIP 104459, isolated from a human vaginal swab. This draft genome consists of 1,993,673 bp, with 36.8% G C content and 2,024 predicted protein-encoding sequences.