Fmoc introduction

Fmoc-Cl, NaHC03, aq. dioxane, 88-98% yield. Diisopropylethylamine is reported to suppress dipeptide formation during Fmoc introduction with Fmoc-Cl. ... 

Fmoc-N3, NaHC03, dioxane, 88-98% yield. This reagent reacts more slowly with amino acids than does the acid chloride. It is not the safest method for Fmoc introduction, because of the azide. 

Benzyloxycarbonyloxy)phenyl]dimethylsulfonium methyl sulfate, NaOH, H20,51-95% yield. " This is a water-soluble reagent for benzyloxy carbamate formation. Analogous reagents for the introduction of BOC and Fmoc were also prepared and give the respective derivatives in similar high yields. 

To accurately determine anchoring, coupling, and cleavage yields, resins are extended further with an internal reference amino acid2 (IRAA lie is used), introduced as its Fmoc derivative by standard coupling methods, at a point before introduction of the handle. 

Introduction of Fmoc The resin was swollen in CH2CI2, and DIPEA (6 equiv) and Fmoc-Cl (4 equiv) were added. The mixture was agitated at rt for 4h and drained and washed [CH2C12 (2 x), MeOH (2 x), CH2C12 (2 x), Et20 (2 x)] and dried under N2. 

Removal of the A-benzyl group of 91 by catalytic hydrogenation and introduction of the Fmoc group proceeded under standard conditions and gave the suitably protected Narg derivative 92 in a total yield of 39%. 

Up to 8 equiv of Fmoc-protected amino add fluoride, at a concentration of 0.3 M in CH2C12, in the presence of DIPEA (1 equiv) were used. Single couplings of 30 min were performed. Only in the synthesis of trichotoxin A-50 were the introduction of Fmoc-Iva-F and the following Aib residue accomplished using double couplings of 1 h each. The yields of the final crude peptides were in the range 60-84%. 

Scheme 13 2-Hydroxy t-methoxybenzyl Amino Acid Residues, Easily Introducted as JV,0-Bis(Fmoc) Derivatives, Inhibit Interchain Association in Solid-Phase Peptide Synthesis18 1...

Synthesis of octreotide and derivative thereof can be carried out by two methods. The first method is synthesized initially by fragment condensation solution phase procedures. The synthetic process of octreotide has been described by Bauer et al. (1). The second method is the synthese by solid-phase procedures. Edward et al. (2) isolated side chain protected octreotide with a total yield of 14% by cleaving the protected peptide from the resin with threoninol. Arano et al. (3) carried out another solid phase method for octreotide, and produced it in overall 31.8% yield based on the starting Fmoc-Thr(tBu)-ol-resin. The basic difference from the other procedures already described is that the introduction of the threoninol is carried out upon the protected peptidic structure (resin-free), which, when appropriately activated, leads quantitatively and without needing to make temporary protections upon the threoninol, to the protected precursor of octreotide, which in turn, with a simple acid treatment leads to octreotide with very high yields. 

A -protected penultimate amino acid (3) protocol for introduction of the second and third residues when the sequence poses a risk of serious chain loss due to diketopiperazine (DKP) formation (4) stepwise chain elongation using Fmoc protocols to complete on-resin assembly of the desired C-terminal-modified peptide and (5) acidolytic cleavage to release the peptide into solution. 

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