Fmoc-Arg (Pbf)-OH is an arginine derivative that uses Fmoc (9-fluorenylmethoxycarbonyl) to protect amino groups and Pbf (2,2,4,6,7-pentamethylbenzofuran-5-sulfonyl) to protect guanidino groups. The development of bio-based Fmoc-Arg (Pbf)-OH from renewable resources can be approached through raw material acquisition and conversion, intermediate synthesis, and final product preparation, with specific pathways as follows:
Renewable Sources of Arginine
Arginine can be obtained from the hydrolysis of natural proteins. Many plant proteins such as soybean protein and wheat protein, as well as animal proteins like collagen, serve as potential raw materials. These proteins are decomposed into amino acid mixtures via enzymatic or acid hydrolysis, followed by separation and purification of arginine using techniques such as ion-exchange chromatography and crystallization. For example, after trypsin hydrolysis of soybean protein, arginine can be adsorbed and separated by cation-exchange resins with a purity exceeding 90%. Additionally, microbial fermentation can produce arginine using renewable sugars like glucose as the carbon source. Genetically engineered microorganisms such as Corynebacterium glutamicum convert sugars into arginine, offering advantages like renewable raw materials and mild reaction conditions.
Renewable Synthesis of Pbf Protecting Group
The synthesis of the Pbf protecting group can attempt to use renewable resources as raw materials. For instance, phenolic compounds extracted from lignocellulose can be used to prepare 2,2,4,6,7-pentamethylbenzofuran-5-sulfonyl chloride (Pbf-Cl) through a series of reactions. First, lignocellulose is hydrolyzed into monosaccharides, which are then converted into phenolic substances like p-cresol via fermentation. Subsequent methylation, cyclization, and sulfonylation reactions yield Pbf-Cl. Although this process is complex, starting from renewable resources ensures good environmental benefits and sustainability.
Green Synthesis Pathway of Fmoc Protecting Group
Fmoc (9-fluorenylmethoxycarbonyl) can be synthesized from fluorene and formaldehyde—renewable raw materials. Fluorene, extracted from coal tar (a byproduct of coal carbonization), is a relatively renewable resource. Fluorene reacts with formaldehyde under alkaline conditions to form 9-hydroxymethylfluorene, followed by chlorination and esterification to introduce a carbonyl group, ultimately synthesizing 9-fluorenylmethoxycarbonyl chloride (Fmoc-Cl) for protecting the amino group of arginine.
Preparation of Bio-based Fmoc-Arg (Pbf)-OH
Using the obtained arginine as a raw material, the side-chain guanidino group is first sulfonylated and protected by reacting with Pbf-Cl under alkaline conditions. Then, Fmoc-Cl or Fmoc-OSu (fluorenylmethoxycarbonyl succinimide) is added, and the α-amino group is Fmoc-protected under the action of a phase-transfer catalyst. After salting and purification, bio-based Fmoc-Arg (Pbf)-OH is obtained. For example, adding the phase-transfer catalyst tetraethylammonium bromide (TEBA) inhibits Pbf-Cl hydrolysis, improving reaction efficiency and increasing the yield from 59% to 72%.
