The total synthesis of frangulanine

Abstract

The reported preparation of the p-ansa compound frangulanine, previously isolated f r o m Rhamnus frangula L., also constitutes the first total synthesis of a fourteen-membered cyclopeptide alkaloid.

Cyclotetrapeptides and cyclopentapeptides: occurrence and synthesis*

“…This procedure has been our method of choice for several years in the synthesis of natural biologically active cyclopeptides. The construction of the cyclopeptide alkaloids zizyphine A and B (54), mucronine (55), dihydrozizyphines A, B (56) and G (57) and frangulanine (58), of the cytostatic cyclotetrapeptides chlamydocine (14) and WF-3161 (15) and of the antibiotic glidobactin (59) have been mostly realized in 80-95'Yo yields by catalytic hydrogenation of the corresponding linear w-Z-aminopentafluorophenyl esters with palladium/charcoal. This cyclisation process takes place on the surface of the palladium, where the free amino group is adsorbed after the Z-group has been cleaved.…”

Biomimetic Synthesis of Azole‐ and Aryl‐Peptide Alkaloids

“…Ring closure as the key step in each of these synthetic routes has been accomplished at different positions of the molecular scaffold (Figure 9.9) [61]. Schmidt et al have introduced a macrolactamization approach based on the activation of a carboxyl-group as a pentafluorophenyl ester, which was further applied to the synthesis of several cyclopeptide alkaloids (Schmidt et al [62][63][64][65][66][67][68][69], Joullié et al [70][71][72][73][74][75][76], Han et al [77][78][79]). …”

“…The simplest ones are cyclic tripeptides containing isodityrosine 60 as a common element (Figure 9.10). Biosynthetically, they are derived from oxidative cyclization of a terminal tyrosine, either at the C-terminus (61) or at the N-terminus (62)(63)(64)(65)(66)(67)(68)(69)(70). These different biphenyl-ether linkages lead to diverse biological activities of otherwise related structures.…”

A Novel Synthetic Approach to Phosphorylated Peptidomimetics

“…Another approach is based on the reaction of glyoxylic acid derivatives with N ‐benzylurethane, which leads to N ‐benzyloxycarbonyl‐2‐ethoxyglycine derivatives. These products, when treated with phosphorus trichloride and triethyl phosphite, afford the corresponding N ‐benzyloxycarbonyl‐substituted phosphorylated glycines, which, on debenzylation with hydrogen on palladium, are applied to peptide synthesis (see, for instance, the preparation of mucronine B and chlamydocin ).…”