Total Synthesis of Piperazimycin A: A Cytotoxic Cyclic Hexadepsipeptide

Abstract

Stark zytotoxisch ist die Titelverbindung 1. Die erste Totalsynthese dieses Naturstoffs beruht auf dem effizienten Aufbau des anspruchsvollen (R,S)‐γClPip/(S,S)‐γOHPip‐Dipeptidfragments sowie einer Makrocyclisierung durch die SN2‐Reaktion einer N‐2‐Chloracetyl‐Einheit mit einem Carboxylat‐Ion.

Total Synthesis of the Proposed Structure of Heronamide C

“…Oxidative cleavage of the olefin in 6 and the following ( E )‐selective Wittig reaction with the use of phosphonium salt 7 8 generated diene 8 as an inseparable 10:1 mixture of ( E )/( Z ) isomers. Double tert ‐butoxycarbonyl (Boc) protection of the amine was necessary for the high ( E ) selectivity 9. Protecting group exchange and the following Horner–Wadsworth–Emmons (HWE) reaction with phosphonate 10 10 gave (2 E )/(2 Z )‐ 12 in a 3:1 ratio, along with 9‐fluorenylmethoxycarbonyl (Fmoc)‐deprotected product 11 .…”

Natural Cyclopeptides as Anticancer Agents in the Last 20 Years

“…Although piperazimycin A was shown with a selective growth inhibition against solid tumor cell lines over leukemia cell lines, the general mode of cytotoxicity was observed in the NCI cell line panel assay [ 190 ]. Further comprehensive studies on piperazimycin A can be proceeded as the total synthesis of piperazimycin A had been accomplished [ 191 ].…”

A Review: Halogenated Compounds from Marine Actinomycetes

“…Total synthesis of streptochlorin started from indole, the synthetic product exhibited potential antifungal activity [20]. Three new hexadepsipeptides piperazimycins A-C (22)(23)(24) were isolated from Streptomyces sp. CNQ-593, which showed cytotoxicity against HCT-116 with an equal IC 50 value of 76 ng/mL [21].…”

“…CNQ-593, which showed cytotoxicity against HCT-116 with an equal IC 50 value of 76 ng/mL [21]. The formation of dipeptide moiety and a macrocyclization by an SN2 reaction were the two key steps in the synthesis of piperazimycin A [22]. Three new chlorinated dihydroquinones (25)(26)(27) Heterologous expression of the CNQ-525-based nap biosynthetic cluster in Streptomyces albus produced 2-deschloro-2-hydroxy-A80915C (28), a new napyradiomycin [24].…”