Isolation, Structure Determination, and Total Synthesis of Hoshinoamide C, an Antiparasitic Lipopeptide from the Marine Cyanobacterium Caldora penicillata

Abstract

Hoshinoamide C (1), an antiparasitic lipopeptide, was isolated from the marine cyanobacterium Caldora penicillata. Its planar structure was elucidated by spectral analyses, mainly 2D NMR, and the absolute configurations of the α-amino acid moieties were determined by degradation reactions followed by chiral-phase HPLC analyses. To clarify the absolute configuration of an unusual amino acid moiety, we synthesized two possible diastereomers of hoshinoamide C and determined its absolute configuration based on a comparison of their spectroscopic data with those of the natural compound. Hoshinoamide C (1) did not exhibit any cytotoxicity against HeLa or HL60 cells at 10 μM, but inhibited the growth of the parasites responsible for malaria (IC50 0.96 μM) and African sleeping sickness (IC50 2.9 μM).

Marine natural products

“…Hoshinoamide C did not exhibit any toxicity against HL-60 or HeLa cells at 10 μM, but inhibited the growth of the parasites responsible for African sleeping sickness (IC 50 2.9 μM) and malaria (IC 50 0.96 μM). 110 Motobamide 224 , a new cyclic decapeptide containing a C -prenylated cyclotryptophan residue, was isolated from a marine Leptolyngbya sp. ; this MNP inhibited the growth of bloodstream forms of Trypanosoma brucei rhodesiense (IC 50 2.3 μM) and showed no cytotoxicity against three human cell lines.…”

“…The first total syntheses of 14 cyanobacterial metabolites were accomplished in 2021, laingolide A 240 , 118 kinenzoline 221 , 108 hoshinoamides A 119 and C 223 , 110 iheyamide A and iheyanone 227 , 113 bromoiesol sulfate A 236 and bromoiesol A 238 , 117 gatorbulin-1 225 , 112 27-deoxylyngbyabellin A, 120 laucysteinamide A, 121 oscillatoxins E and F, 122 and (−)-majusculoic acid. 123 The asymmetric synthesis of four diastereomers of laingolide A 240 led to the unambiguous assignment of the stereochemistry for this MNP.…”

First total synthesis of hoshinoamide A

“…In recent years, Iwasaki and co-workers have reported three novel linear lipopeptide natural products, hoshinoamides A, B [ 11 ] and C [ 12 ], from a microbial metabolite of marine cyanobacterium Caldora penicillata ( Figure 1 ). Hoshinoamides A and B showed potent activities against chloroquine-sensitive Plasmodium falciparum 3D7 with IC 50 values of 0.52 and 1.0 μM, respectively.…”

“…Hoshinoamide C inhibited the growth of the malaria parasites (IC 50 = 0.96 μM) and African sleeping sickness (IC 50 = 2.9 μM). Hoshinoamide C was firstly synthesized from Boc-protected amino acids in liquid phase [12]. Both hoshinoamides A and B are highly methylated polypeptides containing three N-methyl amino acids: N-Me-ʟ-Leu 7 , N-Me-ᴅ-Val 5 and N-Me-ᴅ/ʟ-Phe 2 .…”

First Total Synthesis of Hoshinoamides A

“…In recent years, Iwasaki and co-workers reported three novel linear lipopeptides natural products, Hoshinoamides A, B [11] and C [12] , from a microbial metabolite of marine cyanobacterium Caldora penicillata (Figure 1). Hoshinoamides A and B showed potent activities against chloroquine-sensitive Plasmodium falciparum 3D7 with IC50 values of 0.52 and 1.0 μM, respectively.…”