Fmoc

Fmoc stands for 9-fluorenylmethoxycarbonyl, a carbamate-based amine protecting group widely used in organic synthesis and, in particular, in solid-phase peptide synthesis (SPPS). Introduced and popularized in the 1980s, the Fmoc group provides a base-labile alternative to acid-labile protections, enabling iterative assembly of peptides under mild conditions.

The Fmoc group is stable to many acid-catalyzed steps but is removed by mild base, typically 20% piperidine in DMF at room temperature. Deprotection releases dibenzofulvene, which rapidly reacts with the base or scavengers to form stable adducts, minimizing side reactions during synthesis.

Fmoc contains a strong UV-absorbing fluorene chromophore, enabling straightforward monitoring of deprotection by UV spectroscopy around 300 nm. It can be introduced onto amines as Fmoc chloride, Fmoc-OSu, or via Fmoc-protected amino acids, and it is compatible with a wide range of coupling reagents and side-chain protecting groups used in SPPS.

In the SPPS workflow, resin-bound amino acids bearing Fmoc groups are sequentially deprotected and coupled to build the desired peptide. The base-labile deprotection avoids strong acids, making the method suitable for acid-sensitive sequences and allowing straightforward monitoring of reaction progress. The Fmoc strategy coexists with other protecting-group paradigms and remains a standard approach in peptide chemistry.

Safety and handling considerations apply to common reagents used with Fmoc chemistry, such as piperidine and organic solvents, requiring appropriate personal protective equipment and waste disposal in accordance with laboratory guidelines.