Somatostatin solid-phase synthesis

FIGURE 5.5 Schedule for the solid-phase synthesis of somatostatin, a 14-mer, on 10 g of resin reacted with 5 mequiv of the first amino acid, adapted from J. Rivier, J. Am. Chem. Soc. 96 2986, 1974. Min = time of mixing X2 = two times DCC = dicyclohexylcarbodiimide. Step 4 included 5% of (CH2SH)2 to prevent the oxidation of tryptophan. When the ninhydrin test on an aliquot after step 13 was negative, step 1 followed when positive, steps 9-13 were repeated. 

JEF Rivier. Somatostatin. Total solid phase synthesis. J Am Chem Soc 96, 2986, 1974. 

Table 3 Schedule for DCC Coupling in Solid-phase Synthesis of Somatostatin-14 ...

Table 5 Schedule for eoupling in solid-phase synthesis of somatostatin-28...

Sasl987 Sasaki, Y, Murphy, W.A., Heiman, M.L., Lance, V.A. and Coy, D.H., Solid-Phase Synthesis and Biological Properties of V [CH22NH] Pseudopeptide Analogues of a Highly Potent Somatostatin Octapeptide, J. Med. Chem., 30 (1987) 1162-1166. 

The peptides (17)-(22) were prepared by the usual solid-phase method of peptide synthesis utilizing different resins. The structures of D-Phe (22a) and its conformationally restricted phenylalanine analogue D-Tic (tetrahy-droisoquinoline-3-carboxyIic acid, 22b) positioned at the A-terminal position of the somatostatin analogues are shown. 

Reductive amination was the first method described for amine production on solid phase. It was first mentioned in 1987 by Coy et al. [260,261]. They used a combination of Na(CN)BH3 and HOAc for the subsequent reduction of intermediately formed imides in the synthesis of somatostatin octapep-tide analogs. Due to its early development, this alkylation method has found entry to the synthesis of diverse substance classes like N-terminal-modified peptides, carbohydrate mimetics [262], glycopeptides [263,264], oligonucleotides [265], and of course polyamines [174,175,222,232,248,266,267]. For the same reasons as the amide reduction approach, it is powerful enough to be used in the production of several compound libraries [177,262-264, 268]. 

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