Syntheses of a library of molecules on the marine natural product ianthelliformisamines platform and their biological evaluation

Abstract

Ianthelliformisamines A-C are a novel class of bromotyrosine-derived antibacterial agents isolated recently from the marine sponge Suberea ianthelliformis. We have synthesized ianthelliformisamines A-C straightforwardly by the condensation of (E)-3-(3,5-dibromo-4-methoxyphenyl)acrylic acid and the corresponding Boc-protected polyamine followed by Boc-deprotection with TFA. Further, using this reaction protocol, a library of their analogues (39 analogues) has been synthesized by employing 3-phenylacrylic acid derivatives and Boc-protected polyamine chains through various combinations of these two fragments differing in phenyl ring substitution, double bond geometry or chain length of the central spacer of the polyamine chain (shown in red color). All the synthesized compounds (ianthelliformisamines A-C and their analogues) were screened for antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains. All synthetic analogues of ianthelliformisamine A showed bacterial growth inhibition against both strains (Escherichia coli and Staphylococcus aureus), having MIC values in the range of 117.8-0.10 μM, while none of the synthetic analogues of ianthelliformisamine C as well as the parent compound showed any detectable antibacterial activity. Interestingly, some of the synthetic analogues of ianthelliformisamines A and B exerted a bactericidal effect against both E. coli and S. aureus strains, decreasing viable bacterial count by 99% at concentrations as low as 2 × MIC.

The antimicrobial activity of mono-, bis-, tris-, and tetracationic amphiphiles derived from simple polyamine platforms

“…This stands in stark contrast to the wide variety of bioactive natural products (and derivatives thereof) incorporating multiple primary, secondary, and tertiary amines; common examples include spermine, spermidine, squalamine, and others. [18][19][20][21] While these are generally drawn as neutral compounds, they will have multiple cations at With the ready availability of compounds with three or four tertiary amines at modest commercial cost, 23 we continued on our campaign to correlate bioactivity to amphiphilic structure, specifically the number of cations present, as well as the number and lengths of non-polar sidechains. Our target set of compounds is summarized in Figure 2.…”

Synthesis and Biological Activities of Naturally Functionalized Polyamines: An Overview

“…[171,172] These compounds are all characterized by a 3,5-dibromo-4-methylanisole group linked to a spermine for In 2014, two different synthetic pathways were described to achieve ianthelliformisamines A-C and tokaradine C synthesis. [173,174] The one described here reported a MIC of 12.5 µM against S. aureus DSM 799. [173,174] On the other hand, 86…”

Total Synthesis of Enisorine D and its Analogues

“…Using the general procedure, 3,4,5-tribromo-1H-pyrrole-2-carboxylic acid (synthesized via a literature protocol 20 ) (41 mg, 0.12 mmol, 1 equiv) was reacted with amine 6 (50 mg, 0.12 mmol, 1 equiv) at room temperature for 20 h to afford 4i (52 mg, 53%) as a transparent liquid. Using the general procedure, (E)-3-(3,5-dibromo-4-methoxyphenyl)acrylic acid (synthesized via a procedure reported earlier by our group 19 ) (39 mg, 0.12 mmol, 1 equiv) was reacted with amine 6 (50 mg, 0.12 mmol, 1 equiv) at room temperature for 20 h to afford 4j (60 mg, 86%) as a colorless liquid.…”

“…Using the general procedure, (E)-3-(2,4,6-tribromo-3-methoxyphenyl)acrylic acid (synthesized via a procedure reported earlier by our group 19 ) (49 mg, 0.12 mmol, 1 equiv) was reacted with amine 6 (50 mg, 0.12 mmol, 1 equiv) at room temperature for 15 h to afford 4l (85 mg, 88%) as a pale blue solid.…”