Fragment condensation in solution

Fmoc-fiaflttwnfc-fraBmenti-OH Fifwc-fragm ntrfraonwnti-0-Q 

Protocol 7. Synthesis of 2-chlorotrityl esters of protected fragments 

Dissolve the protected fragment in the highest possible concentration in DMF and add 10 eq DIPEA. 

Prepare a 1 M solution of 5 eq, with respect to the protected fragment, of 2-chlorotrityl chloride in DCM. 

Add the chloride solution dropwise to the stirred peptide solution and continue stirring for 6-12 h at RT. Check for completion of the esterification by TLC. 

---

The template was synthesized by classical fragment condensation in solution 39114 (see Section 13.1.1.1). Briefly, the condensation of two peptide intermediates, Fmoc-A2bu(COCH2ONHAloc)-Lys(Boc)-OH and NH2-A2bu(COCH2ONHBoc)-Pro-Gly-OMe, afforded the pentapeptide Fmoc-A2bu-... 

Synthesis of dynorphin B also has been reported by using fragment condensation in solution-phase (133). 

The DCC/HOSu proceduref l has been extensively apphed to fragment condensations in solution. In racennization-prone coupling steps this procedure was generally found to be superior to the DCC/HOBt method (see Section 3.5.1.2.2) even if HOBt (14) is more efficient as an additive in terms of acylation rates. 

The use of less basic and sterically hindered amines [e.g., collidine or 2,6-di-tert-butyl-4-(dimethylamino)pyridine ], the avoidance of preactivation, and the use of less polar solvent systems are additional appropriate strategies for the suppression of racemization. Except for fragment condensations in solution and couplings involving racemization-prone derivatives, the addition of HOXt to the reaction mixture has no pronounced effect on a uronium salt mediated racemization/epimerization, in contrast to the striking effects of HOAt on epimerization caused by PfPyU and haloamidinium salts such as CIP or TFFH (Section 3.8.1.2.1). 

Machauer, R. Waldmann, H. Synthesis of lipi-dated eNOS peptides by combining enzymatic, noble metal- and acid-mediated protecting group techniques with solid phase peptide synthesis and fragment condensation in solution. Chemistry... 

Peptide chain built by fragment condensation in solution. 

An alternative to the synthesis of proteins by classical fragment synthesis in solution or by solid-phase synthesis on a support is the use of enzyme-catalyzed condensation of amino acids or peptides. This possibility was first demonstrated in 1938 91 with the synthesis of poorly soluble benzoyl-leucyl-leucine anilide by papain catalysis. After many years, this approach was extended to the preparation of peptide hormones such as Leu-enkephalin 92 and dynorphin(l -8).[93 This was made possible by the use of highly purified enzymes and by careful control of reaction conditions. The basic principles of protease-catalyzed peptide bond formation have been discussed.194 ... 

On the interaction of 1,3-diketones with dihydrazides of oxalic and malo-nic acids, the condensation products have been obtained in a molar ratio of 2 1 (88ZOR1823). In the solid state, they exist as the bispyrazolines 77 but in solution, equilibria are observed. These equilibria occur with the participation of the bispyrazoline tautomer, involving two diastereomers, and also of tautomers containing hydrazone and/or enhydrazine fragments. 

---