Efficient Construction of the Carbon Skeleton of the Novel Polyoxazole-Based Cyclopeptide IB-01211 via a Biomimetic Macrocyclisation

Abstract

An efficient construction of the entire carbon skeleton of the novel polyoxazole-based natural product IB-01211 was developed which featured a biomimetic macrocyclisation of an w-amino acid tethered through two bisoxazole units as the key step.

Muscarine, imidazole, oxazole, and thiazole alkaloids

“…A biomimetic macrocyclisation strategy has been developed for the efficient construction of the full carbon skeleton of the polyoxazole-based cyclic peptide IB-01211 363, isolated from the marine microorganism strain ES7-008. 311 Marine actinomycete strain NPS008920, a member of the new genus Marinispora, has produced three novel 4-oxazolidinone derivatives, lipoxazolidinones A 364, B 365, and C 366, which showed broad spectrum antimicrobial activity similar to that of the commercial antibiotic lenezolid (Zyvox Ò ), a 2-oxazolidinone derivative. 312 Two unusual linear hybrid polyketide-nonribosomal peptide antibiotics, ariakemicins A 367 and B 368, have been isolated from the fermentation extract of the marine gliding bacterium Rapidithrix sp.…”

Telomestatin: Formal Total Synthesis and Cation-Mediated Interaction of Its seco-Derivatives with G-Quadruplexes

“…The unique hepta-oxazole structure of telomestatin has spawned a substantial amount of effort on the synthesis and G-quadruplex binding properties of a number of macrocycles containing three, four, six, or seven oxazole rings, either linked directly (as in telomestatin) or via amide bonds. − However, despite all this work on analogues, and the clear interest in the biological activity of telomestatin itself, to date there have been only two syntheses of the natural product reported, the first in a patent, , although a number of other approaches to poly oxazoles have been described. − Oxazole-containing natural products continue to capture the imagination of chemists, not only because of their structural diversity but also their biological activity, and therefore remain topical targets for synthesis. We now describe a formal total synthesis of telomestatin employing rhodium carbene chemistry to generate six oxazole rings, and the potent G-quadruplex stabilizing activity of its seco -derivatives.…”

Diversity-oriented synthesis of analogues of the novel macrocyclic peptide FR-225497 through late stage functionalization

“…The two termini of 11 were then sequentially deprotected involving ester hydrolysis of 11 → 12 followed by N-deprotection of the latter leading to a crude TFA salt in readiness for a subsequent macrocyclization. The macrocyclization proceeded well under our previously developed conditions [ 21 ] to deliver the template 13 in an acceptable yield of 73% over two steps.…”