Synthetic peptides related to caerulein. Note 2

Fifty Years of Chemical Research at Farmitalia

“…The synthetic scheme involved the preparation of ceruletide ( 20 ) from the condensation of intermediates 18 and 19 . Shortly afterwards, a synthetic analogue program produced over 60 compounds whose biological screening in a number of test systems allowed conclusions to be drawn about the structure–activity relationships in an attempt to dissociate the different activities that constitute the pharmacological spectrum of the natural peptide 41…”

“…Shortly afterwards, a synthetic analogue program produced over 60 compounds whose biological screening in a number of test systems allowed conclusions to be drawn about the structureactivity relationships in an attempt to dissociate the different activities that constitute the pharmacological spectrum of the natural peptide. [41] An important group of peptides isolated and synthesized in the early 1970s was that of bombesin and bombesin-like alytesin, litorin, and their synthetic analogues. Bombesin, a 14-amino-acid peptide homologous to the C terminus of mammalian gastrin-releasing peptide (GRP), and alytesin were isolated from the methanol extracts of the skin of European frogs of the genuses Bombina and Alytes.…”

“…[119] Analogues modified in the aglycone moiety were obtained by total synthesis (Scheme 7), [120a] using a variant of the reaction sequence devised by C.-M. Wong. [121] (R)(À)-6-Acetyl-1,4-dimethoxy-6-hydroxytetralin (41), obtained upon crystallization of the Schiff base of the starting racemic compound with (À)-1-phenylethylamine and subsequent hydrolysis of the enantiomeric products, was condensed with phthalic anhydride allowing the direct formation of 7-deoxy-4-demethoxydaunomycinone 42, which was first protected as ethylidene ketal 43, then converted to the corresponding 7-hydroxylated compound 44 by radical bromination and hydrolysis. Glycosidation of 44 gave 45.…”