Fluorenylmethoxycarbonyl chlorides

A recently described approach involving zinc dust for eliminating acid allows acylation by 9-fluorenylmethoxycarbonyl chloride without dimer formation. The amino acid is dissolved in acetonitrile with the aid of hydrochloric acid, and zinc dust is added to destroy the acid and deprotonate the zwitter-ion, reducing the protons to gaseous hydrogen (Figure 3.16). Acylation is effected in the presence of zinc dust, which reduces the proton that is liberated by the reaction as soon it is formed. See Section 7.7 for another possible impurity in Fmoc amino acids.34,36-39... 

A reactor containing 2-amino-1,3-propanediol (10.0 mmol) and 25 ml of IM NaOH was cooled to 0.2°C and treated with A-(9-fluorenylmethoxycarbonyl)chloride (13.1 mmol) dissolved in 10 ml of CH2CI2 over a 1 hour period. The solution was stirred for 1 hour at 0°C and 4 hours at ambient temperamre. The organic solvent was evaporated and the aqueous residue poured into 70 ml of EtOAc. The organic phase was isolated, washed with 5% aqueous HCl, dilute NaHC03, brine, and dried. The mixture was concentrated, the residue re-crystalhzed in chloroform, and the product was isolated. 

Recently, we exploited the unique spectroscopic properties of AW to probe the disulfide-coupled folding of the hirudin N-terminal domain 1-47 and the binding to its the target enzyme, thrombin [90]. Before chemical synthesis, the resolution of the commercially available enantiomeric mixture of AW was carried out by treating the racemic mixture with acetic anhydride and subsequent enantioselective deacylation with immobilized Asperigillus oryzae acylase-I to yield L-AW (Scheme 9-1). Purified L-AW was then reacted with 9-fluorenylmethoxycarbonyl chloride... 

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