Automated glycan assembly using the Glyconeer 2.1 synthesizer

Hahm, Heung Sik; Schlegel, Mark K.; Hurevich, Mattan; Eller, Steffen; Schuhmacher, Frank; Hofmann, Johanna; Pagel, Kevin; Seeberger, Peter H.

doi:10.1073/pnas.1700141114

Cited by 102 publications

(99 citation statements)

References 23 publications

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“…This presents the strategic opportunity for collective efforts to be deployed to extensively optimize these two reactions and ultimately reach highly generalized conditions, as was previously achieved for iterative peptide 198 and oligonucleotide synthesis, 199 and is now being increasingly realized for oligosaccharides. 200 …”

Section: Automation Of Small Molecule Synthesismentioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

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Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the “building block approach”, i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach.

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Section: Automation Of Small Molecule Synthesismentioning

confidence: 99%

Towards the generalized iterative synthesis of small molecules

2018

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“…Certainly, the sheer size of the arabinogalactan oligomer opens new directions for the preparation of homogenous oligosaccharides and is a demonstration of the power of modern chemical synthesis. With the recent developments in automated oligosaccharide synthesis, and the combination of chemical and enzymatic methods, one can anticipate that oligosaccharides with a three‐digit monosaccharide count are just around the corner.…”

Section: Methodsmentioning

confidence: 99%

Size Matters: Chemical Synthesis of a Homogenous Arabinogalactan 92‐mer

Walczak

Zhu

2017

ChemBioChem

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“…[64] As described below, handling air sensitive reactions, on-demand synthesis of multiple different pharmaceuticals, and high throughput synthesis of various targets have all been achieved with this approach.…”

Section: One Machine – Many Small Moleculesmentioning

confidence: 99%

The Molecular Industrial Revolution: Automated Synthesis of Small Molecules

2018

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The eighteenth and nineteenth centuries marked a sweeping transition from manual to automated manufacturing on the macroscopic scale. This enabled an unmatched period of human innovation that helped drive the Industrial Revolution. The impact on society was transformative, ultimately yielding substantial improvements in living conditions and lifespan in many parts of the world. During the same time period, the first manual syntheses of organic molecules was achieved. Now, two centuries later, we are poised for an analogous transition from highly customized crafting of specific molecular targets by hand to the increasingly general and automated assembly of many different types of molecules with the push of a button. Automation of customized small molecule synthesis pathways is already enabling safer, more reproducible, and readily scalable production of specific targets, and general machines now exist for the synthesis of a wide range of different peptides, oligonucleotides, and oligosaccharides. Creating general machines that are similarly capable of making many different types of small molecules on-demand, akin to that which has been achieved on the macroscopic scale with 3D printers, has proven to be substantially more challenging. Yet important progress is being made toward this potentially transformative objective with two complementary approaches: (1) automation of customized synthesis routes to different targets via machines that enable use of many different reactions and starting materials, and (2) automation of generalized platforms that make many different targets using common coupling chemistry and building blocks. Continued progress in these exciting directions has the potential to shift the bottleneck in molecular innovation from synthesis to imagination, and thereby help drive a new industrial revolution on the molecular scale.

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Automated glycan assembly using the Glyconeer 2.1 synthesizer

Cited by 102 publications

References 23 publications

Towards the generalized iterative synthesis of small molecules

Towards the generalized iterative synthesis of small molecules

Size Matters: Chemical Synthesis of a Homogenous Arabinogalactan 92‐mer

The Molecular Industrial Revolution: Automated Synthesis of Small Molecules

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