Structure of complestatin, a very strong inhibitor of protease activity of complement in the human complement system

Synthesis of Linear Tripeptides for Right-Hand Segments of Complestatin

“…22,23) in the presence of CsF, collidine, the same yield (35%) was obtained, but the reaction rate was retarded to 18 h. In the case of t Bu 3 P, when using the dioxane, NMP as a solvent, the yield was also very low. It is reported that Ph 3 As accelerates the rate of transmetalation more than PPh 3 (Ph 3 As : Ph 3 Pϭ 100 : 1).…”

“…Stille coupling can be performed under neutral reaction conditions, which should prevent racemization of dichlorohydroxyphenylglycine. Furthermore, Fu et al discovered 31) Pd/P(tBu) 3 , which is a mild, highly reactive and general catalyst for Stille coupling. This catalyst would be effective for macrocyclic carbon-carbon coupling, which is assumed not to be easy in a sterically hindered compound.…”

“…H-NMR in 1989, 3) and the absolute structure of the amino acid constructing the A, C, E ring was also determined to be each L-form by hydrolysis of the amide bond. In 1994, 1 was isolated by Matsuzaki et al from Streptomyces sp.…”

“…4) The absolute stereostructure of chloropeptin 2 was determined in 1996 5) by combination of acid hydrolysis, molecular dynamics and NMR spectroscopy. According to the published paper concerning the planar and absolute stereostructure of complestatin 1 and chloropeptin 2 3,5) they are bismacrocyclic hepta peptides and they differ only at the position of the phenyl-indole ring junction D, F (Fig. 1).…”

Chapter 19 In Vitro Studies of Phenol Coupling Enzymes Involved in Vancomycin Biosynthesis

“…Such aromatic C-O-C and C-C cross-links, however, occur more widely in Nature, for example, in the closely related bacterial metabolites complestatin (Seto et al, 1989), kistamicin (Naruse et al, 1993) and chloropeptin (Matsuzaki et al, 1994), as well as in peptidic natural products such K-13 (Yasuzawa et al, 1987), bouvardin (Jolad et al, 1977) and the related plant metabolites RA-I-XVI (Hitotsuyanagi et al, 2004), OF4949 (Sano et al, 1986), the arylomycins (Holtzel et al, 2002), the biphenomycins (Uchida et al, 1985), the TMC-95 family (Kohno et al, 2000), and RP-664536 (Helynck et al, 1998).…”