Analysis of 9-fluorenylmethoxycarbonyl (FMOC) loading of solid-phase synthesis resins by gas chromatography

✍ Scribed by William S. Newcomb; Tracy L. Deegan; Wendy Miller; John A. Porco Jr.

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 98 KB
• Volume: 61
• Category: Article
• ISSN: 0006-3592
• DOI: 10.1002/(sici)1097-0290(199824)61:1<55::aid-bit10>3.0.co;2-8

✦ Synopsis

Base-catalyzed cleavage of the 9-fluorenylmethoxycarbonyl (FMOC) group and subsequent analysis by UV spectrophotometry is commonly employed to measure the ''loading'' of functional groups on solid support. Recent work suggests that 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) may be superior to piperidine (the most commonly used base for the cleavage) for quantitative analysis by UV. We have compared deprotection of FMOCbearing compounds by both DBU and piperidine, and have observed by GC-MS the formation of a dibenzofulvene-piperidine adduct (piperidine deprotection), and the formation of unassociated dibenzofulvene (DBU deprotection). We have further been able to use GC analysis of dibenzofulvene produced in the DBU deprotection mixture in a quantitative analysis of resin loading, which gave results comparable to UV methods. Sample preparation for this method has been automated using the Nautilus 2400 organic synthesizer to reduce the amount of operator time and increase throughput of sample analysis.