VaporSPOT: Parallel Synthesis of Oligosaccharides on Membranes

Abstract

Automated chemical synthesis has revolutionized synthetic access to biopolymers in terms of simplicity and speed. While automated oligosaccharide synthesis has become faster and more versatile, the parallel synthesis of oligosaccharides is not yet possible. Here, a chemical vapor glycosylation strategy (Vapor-SPOT) is described that enables the simultaneous synthesis of oligosaccharides on a cellulose membrane solid support. Different linkers allow for flexible and straightforward cleavage, purification, and characterization of the target oligosaccharides. This method is the basis for the development of parallel automated glycan synthesis platforms.

VaporLIFT: On‐Chip Chemical Synthesis of Glycan Microarrays

“…Initial vapor glycosylation of the transferred mannose building block 6 failed, when using the previously reported vapor glycosylation setup and conditions. [ 31 ] We hypothesized that this failure was a result of the glass vapor glycosylation chamber and the limited cooling capacity of the air‐cooled thermoelectric element. The glass wall shields the glass solid support and prevents direct cooling.…”

“…First, a commercial photocleavable linker (see Section SE, Supporting Information) was covalently attached via amide bond to the slide prior to linker 1 and glass slide 8 was subjected for in solution glycosylation under inert conditions in a glass chamber (Figure S8, Supporting Information) using excess mannopyranoside 6 . Detection of disaccharide product 9 was achieved after cleavage under UV‐light irradiation (365 nm) and analysis by MALDI‐ToF MS. For direct glycosylation without prior attachment of a sugar moiety on the solid support, another photocleavable linker was synthesized, [ 31 ] and covalently attached to the amino‐functionalized glass slide (Section SE, Supporting Information). Acceptor slide 10 was glycosylated after transfer of glycosylating agent 6 over the entire acceptor slide, followed by vapor glycosylation.…”

“…Synthesis of Glycosyl Donor BBs : Glycosyl donor 14 was prepared from a commercially available precursors as reported in Supporting Information, while all remaining glycosyl donors ( 6 , 12, 13, 15‒20 ) where synthesized following already established protocols. [ 31,33,37–39 ]…”

“…This method combines the high‐throughput capabilities of laser‐induced forward transfer (LIFT) [ 30 ] with the vapor synthesis method (vaporSPOT) for the parallelization of chemically demanding reactions. [ 31 ] LIFT can generate spot patterns containing matrix‐embedded chemical building blocks (BBs) on a solid support with high precision, but is limited to robust reactions such as amide bond formation. In contrast, the vapor synthesis method enables parallelization of temperature and moisture‐sensitive chemical glycosylation reactions, but is limited in throughput.…”

Ag-Catalyzed Switchable Synthesis of Site-Specifically Functionalized Pyrroles via Azafulvenium Intermediates

“…4 However, these methods often involve multiple steps, intricate procedures, and limited starting materials. Moreover, most previously developed techniques follow conventional parallel synthesis 5 routes, yielding only a single type of pyrrole scaffold. Recently, chemists have begun to focus on integrating synthetic efficiency into the development of synthetic methods, which also has guiding significance in the development of methods for synthesizing pyrrole pharmacophores.…”