Macrocyclization studies and total synthesis of cyclomarin C, an anti-inflammatory marine cyclopeptide

Synthesis of New Cyclomarin Derivatives and Their Biological Evaluation towards Mycobacterium Tuberculosis and Plasmodium Falciparum

“…Thus, the N-terminal Cbz group of 19 [24] wasc leaved by hydrogenation, allowing the free amine to be coupledw ith the N-Alloctryptophan derivativest ot he corresponding hexapeptides 23 a-e utilizing2 -bromo-1-ethyl-pyridiniumt etrafluoroborate (BEP). [22,23] For this purpose, the C-and N-terminally deprotected peptides were slowly added to the coupling reagent via transfer cannula. To complete the synthesis, the methyl ester at the C-terminuswas saponified with lithium hydroxide.…”

“…using two equivalents of benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate( PyBOP) and DIPEA under high dilution conditions (1 mm). [22,23] For this purpose, the C-and N-terminally deprotected peptides were slowly added to the coupling reagent via transfer cannula. The final step, cleavage of the TBS ether using TBAF, led to our first small library of ten analogues.…”

“…Sensitivity retains for MDR strains, which implies an ovel moleculart arget of the compound family. [21] In 2004, the first total synthesis of cyclomarin Cw as published by Yaoe tal., [22,23] paving the path for Barbie and Kazmaierf or the first total synthesis of cyclomarin A, [24] Ca nd D [25] as well as the slightly simplified derivative desoxycyclomarin C ( Figure 1). [19] Additionally,c yclomarin As hows an impressive activity against Plasmodium falciparum (Pfalcp)w ith an inhibitory concentrationint he low nanomolar range.…”

“…The distinctive bioactivitieso ft he cyclomarins have turned great interest into the synthesis of thesen atural products. [21] In 2004, the first total synthesis of cyclomarin Cw as published by Yaoe tal., [22,23] paving the path for Barbie and Kazmaierf or the first total synthesis of cyclomarin A, [24] Ca nd D [25] as well as the slightly simplified derivative desoxycyclomarin C( Figure 1). [26] Biological characterization of the natural productsa nd some semi-synthetic analogues at Novartis provided useful information regarding the structure-activity relationship (SAR) of the cyclopeptides ( Figure 2).…”

Chemistry and biological activity of azoprenylated secondary metabolites

“…cyclomarines) (Sugiyama et al, 2001). Other structurally similar derivatives were also synthesized, starting from tryptophan or functionalized indoles (Wen et al, , 2005Sugiyama et al, 2002;Hansen et al, 2006;Della Sala et al, 2006). Biosynthetic studies of these simple indole alkaloids were performed very recently in Aspergillus fungi.…”