Microreactor Array Assembly, Designed for Diversity Oriented Synthesis Using a Multiple Core Structure Library on Solid Support

Abstract

The application of spatially encoded principles in solid phase combinatorial synthesis requires no chemical or physical coding strategies. The resulting products are encoded by their position inside the array and their synthesis history. The advantages of microreactor arrays for solid phase synthesis as one of the embodiments in the field of microreaction technology are discussed. Here, we review the reactor design, necessary process steps, and a strategy for the diversity oriented array synthesis. In particular, the glass-made microreactor and its assembly for 1563 parallel solid phase reactions, which can be performed at temperatures up to 120 8C, are described. Bead loading and liquid handling steps were adapted to this array. The production of large libraries demands suitable synthesis protocols and building blocks. The optimization of appropriate synthesis conditions is a time-consuming process. A multiple core structure library approach for the efficient synthesis of diverse heterocyclic libraries is described. The aim of this work was to prove the feasibility of the glass-microreaction array for massive parallel library synthesis.

Organische Reaktionen in Mikrotröpfchen: Analyse von Reaktionsbeschleunigungen durch Massenspektrometrie

“…Im vergangenen Jahrzehnt ist die Mikroreaktor‐Technologie, wie Mikroemulsionen, Mikroreaktoren auf Array‐Basis und Mikrofluidik‐Systeme, auf großes Interesse gestoßen, da sie die Kompartimentierung von Reaktionen in Volumina im Nanoliter‐ bis Mikroliterbereich ermöglicht. Obwohl diese Technik hervorragende Anwendungen hat, war ihre Erforschung nur selten auf die Reaktionsbeschleunigung gerichtet.…”

The Eschenmoser coupling reaction under continuous-flow conditions

“…The carbon–carbon coupling occurs between these building blocks as shown in Scheme 1 . Due to the ease of accessibility of the building blocks and the usually high-yielding S-alkylation step, the Eschenmoser coupling is an interesting reaction for diversity-oriented combinatorial synthesis [ 15 – 17 ].…”