The mission of Apeiron Synthesis is to fully realize the potential of olefin metathesis in synthetic chemistry, with efficient and cost-effective solutions for R&D and commercial manufacturing processes – solutions that can benefit a wide range of industries, including agrichemicals, fine chemicals, flavor and fragrances, polymers and Pharma/Biopharma.

Catalytic olefin metathesis technology offers chemists remarkable efficiency over traditional methods for building complex molecules - fewer synthetic steps and byproducts, reduced waste, and higher reaction concentrations - significantly lowering costs. Apeiron has developed a growing portfolio of over thirty high performance metathesis catalysts, available in milligram to multi-kilogram quantities, designed to accommodate a wide range of applications. With an uncompromising commitment to the design and use of robust new catalysts, our team of specialists is available to help customers transform their chemistry with metathesis technology.

Olefin metathesis was discovered in the 1950’s as “olefin disproportionation”, with primarily industrial applications using harsh conditions. The first generations of homogeneous metathesis catalysts enabled transformations using relatively mild reaction conditions, with the potential to revolutionize the way chemists synthesize organic molecules – recognized as such with the 2005 Nobel Prize for Chemistry awarded to pioneers in the field.

Apeiron is now leading the way to diverse new applications to transform catalytic olefin metathesis from a technology with high potential to an important part of every chemist’s toolkit.

Apeiron’s product offerings include an array of ruthenium cata-lysts designed for effective use in a broad range of metathesis processes, suitable for applications in R&D as well as in large scale production. We combine the latest scientific advance-ments with customer-driven new product development. Our technology platform is highly modular, enabling us to manu-facture catalysts incorporating process-specific structural modifications in the labile and non-labile ligands. Apeiron takes advantage of both proprietary technology that is the result of an in-house research program and external intellectual prop-erty licensed from leading European industrial and academic partners.

We specialize in modifications of the nonlabile (NHC) ligand to append customized utility tags - affording novel catalyst traits for process-specific requirements, such as altered solubility profiles, simpler post-reaction work-up or easier removal of ruthenium residues from products.

About Us

Transforming your chemistr y

The Apeiron Advantage

Apeiron Synthesis / © 2016

About Us

Apeiron endeavors to offer the optimum metathesis catalyst for the application at hand. This is a non-trivial goal since every trans-formation is different, with a unique combination of substrate(s) and reaction conditions. To address this challenge Apeiron has developed a broad and growing portfolio of unique, patented and patent pending catalysts that can satisfy an increasingly broad range of metathesis substrates and conditions. In addition, Apeiron has the capability to design process specific catalysts to deliver value to customers undertaking metathesis chemistry in operations spanning R&D, process development, and production.

Product and Service Offerings

Major Advantages of Apeiron Catalysts:

• High turnover number (TON up to 90,000) and turnover frequency (TOF up to 6,000 min-1)• Functionality across temperatures from 0 up to 140 ⁰C• Compatibility with various non-polar and polar solvents, including water• Easy and irreversible deposition on various solid supports – catalyst heterogenization – e.g., for flow chemistry or other

heterogeneous catalyst applications• Easy removal of residual ruthenium from reaction mixture • Initiation control for polymer applications

• High Throughput Screening of Apeiron metathesis catalysts for customer-specific synthetic needs• Optimization of customer metathesis reaction or process• Development and manufacture of process-specific catalyst for customer product development• Synthetic route design and optimization for efficient implementation of metathesis • Intermediate/product scale-up/production (kg, MT capacity)

• Proprietary tube-in-tube™ flow reactor for metathesis under continuous flow mode (allowing removal of gaseous byproducts)• Proprietary scavengers for ruthenium removal

Our Catalysts

Our Services

Supportive Technologies for Olefin Metathesis

Apeiron’s plant is configured to deliver catalysts in Kgquantities within 3-4 weeks.

All of our core catalysts are available in milligram-gram quanti-ties from Strem Chemicals. For other catalysts, contact us for an order inquiry and watch for new product introductions in the Strem online catalog.

For R&D For production

www.strem.com

Apeiron Synthesis / © 2016

Core Catalysts

nitro-GrelaNitro-Grela catalyst is a stable olefin metathesis initiator active in various ring-closing, cross, and enyne metathesis reactions. Its efficiency has been proved in synthesis of numerous fine chemicals, natural products, and biologically active compounds. A New Highly Efficient Ruthenium Catalyst for Metathesis Reaction; Grela, K.; Harutyunyan, S.; Michrowska, A. Angew. Chem. Int. Ed., 2002, 41, 4038–4040

PCT/EP2003/011222

RuCl

ClO

NN

NO2

AquaMet Stable olefin metathesis initiator with very good solubility in neat water. AquaMet efficiently promotes ring-closing, cross, and enyne metathesis reactions of water soluble substrates.Highly Active Catalysts for Olefin Metathesis in Water; Skowerski, K.; Szczepaniak, G.; Wier-zbicka, C.; Gułajski, Ł.; Bieniek, M.; Grela, K. Catal. Sci. Technol., 2012, 2 (12),2424–2427

PCT/EP2013/053967

RuCl

ClO

NN

N

NCl

StickyCat ClEasy and efficient removal of residual ruthenium from metathesis products, thanks to very high polarity and affinity to silica gel, and high efficiency in various types of metathesis reactions.Easily Removable Olefin Metathesis Catalysts; Skowerski, K.; Wierzbicka, C.; Szczepaniak, G.; Gułajski, Ł.; Bieniek, M.; Grela, K. Green Chem., 2012, 14 (12), 3264–3268

PCT/EP2013/053967

RuCl

ClO

NN

ClN

GreenCatGreenCat efficiently promotes various olefin metathesis transformations in non-degassed and non-dried ACS-grade green solvents such as EtOAc, CPME, and i-PrOH.Efficient, Durable and Reusable Olefin Metathesis Catalysts with High Affinity to Silica Gel; Skowerski, K.; Kasprzycki, P.; Bieniek, M.; Olszewski, T. K. Tetrahedron, 2013, 69, 7408–7415.

PCT/EP2013/062435

RuCl

ClO

NN

O

NO

RuO

Cl

P

NN

3

LatMet LatMet catalyst is a highly efficient, latent catalyst which requires chemical and thermal activation in order to initiate catalytic activity. Its characteristics are espe-cially suitable to mold polymerization of reactive monomers such as dicyclopenta-diene (DCPD).Chelating Ruthenium Phenolate Complexes—Synthesis, General Catalytic Activity and Applications in Olefin Metathesis Polymerization; Kozłowska, A.; Dranka, M.; Zachara, J.; Pump, E.; Slugovc, C.; Skowerski, K.; Grela, K. Chem. Eur. J. 2014, 20, 1–7

PCT/EP2013/065839

Apeiron Synthesis / © 2016

North AmericaApeiron Synthesis, Inc Cambridge Innovation Center, 1 Broadway , Cambridge, MA 02142 USA

Grazyna Szymanska, PhDGlobal Business Developmentgrazyna.szymanska@apeiron-synthesis.comCell: (+1) 781-608-5859

EuropeApeiron Synthesis S.A. Wroclaw Technology Parkul. Duńska 9, 54-427 WrocławPoland

Joanna DrygajłoSales Manager and Technical Support joanna.drygajlo@apeiron-synthesis.comTel.: (+48) 71-798-5621

Validation by IndustryEach of the Apeiron’s catalysts has been extensively tested and some have become industry standards. Our catalysts have dem-onstrated clear superiority with respect to reaction time, temperature, dilution factor, reactivity and selectivity.Apeiron’s products and services save our customers’ time and money by transforming conventional chemistry towards more efficient, sustainable and profitable processes featuring olefin metathesis technology.

Synthesis of Hepatitis C Antiviral Agent BILN 2061 by Boehringer Ingelheim

Selected examples of products synthesized with the use of Apeiron’s catalyst

400 kg

nitro-Grela0.5 mol%Roche Inc.US 2009/0163706 A1

nitro-Grela0.2 mol%Boehringer Ingelheim Int.WO 2008/009671 A1N

O ON

O

ON

F

O

HN CO2Et

O

BocHN

• 18 times lower manufacturing costs• 50 times lower catalyst loading• 16 times shorter reaction time

• 20 tmes lower residual Ru in the product• 20 times lower volume of solvent• 7 times lower production of waste

Advantages of using nitro-Grela RCM catalyst over 1‘st generation process

nitro-Grela offered by Apeiron0.1 mol%

0.4 kg

BILN 2061(Ciluprevir™)

Catalyst usedin 2’nd generation process

Hoveyda-Grubbs 1’st generation5.3 mol%21.6 kg

Catalyst usedin 1’st generation process

metathesis’ product

O

O

NCO2Me

O

NH

O

O

N H

N

S

NNH

OMe

RuCl

ClO

P3

RuCl

ClO

NN

NO2

[1] Nicola, T.; Brenner, M.; Donsbach, K.; Kreye, P. Organic Process Research & Development, 2005, 9, 513–515[2] Farina, V.; Shu, C.; Zeng, X.; Wei, X.; Han, Z.; Yee, N. K.; Senanayake, C. H. Organic Process Research & Development, 2009, 13, 250–254

400 kg

Apeiron Synthesis / © 2016