Total synthesis and stereochemical revision of xiamenmycin A

Abstract

The relative and absolute configurations of xiamenmycin A, a benzopyran compound isolated from Streptomyces xiamenensis 318 with a highly potent anti-fibrotic activity, have been characterized through the total synthesis. The key steps include the construction of the 3-chromanol moiety via Sharpless epoxidation followed by regio- and diastereo-selective cyclization and introduction of the threonine moiety at a later stage via Pd-catalysed aminocarbonylation in a one-pot procedure. The stereochemical assignment of natural xiamenmycin A has been accordingly revised to be 2R, 3S, 3'S, 4'R.

Marine natural products

“…and an unidentied metagenome clone 178 and 179. 86 Several structure revisions were reported during 2016, including thiasporine A 180, 87 xiamenmycin A 181, 88 and xiamenmycin C 182, 89 halichomycin 183, 90 and iso-naseseazine B 184. 91 Furthermore, total syntheses of a number of bioactive or architecturally attractive MNP scaffolds have also been successfully completed and reported in 2016.…”

Enantioselective Synthesis of 3‐Fluorochromanes via Iodine(I)/Iodine(III) Catalysis

“…Pertinent examples under the auspices of chiral phase transfer catalysis, [6] and phosphoramidate catalyzed bromo-and iodocyclizations are noteworthy. [7] To complement these elegant solutions,e fficient entry to the parent 3-fluorochromane scaffold is needed to complete the bioisosterism continuum [H % F % OH] (Figure 1, center) [8] and explore the potential of the unsubstituted ring system in drug discovery.T he vicinal relationship of fluorine to the ring oxygen will result in stabilizing hyperconjugative interactions (s C-H !s C-F *), [9] that manifest themselves in the conformation of these drug modules.T he broad spectrum of biological activities mediated by chromanes is ap owerful motivator to address this deficiencyi nc ontemporary catalysis.P ertinent examples include the antidiabetic agent Englitazone (1), [10] Xiamenmicin (2)w hich exhibits anti-inflammatory properties, [11] and the venerable antioxidant Tocopherol (vitamin E) (3). [12] Thechemotherapeutic potential of (+ +)-Catechin (4) [13] further adds to this clinical diversity (Figure 1, top).…”

Total synthesis of xiamenmycin C and all of its stereoisomers: stereochemical revision

“…However, the comparison of NMR spectral data of compound (±) 8 with the reported natural xiamenmycin C showed that there were large deviations in the 13 C-NMR spectra for the 9-position carbon atom (Δδ = 4.9 ppm) and 15-position carbon atom (Δδ = 2.5 ppm) ( Table 1). The results suggested that the stereochemistry of the proposed xiamenmycin C may be incorrect [1,5].…”

“…In our previous studies, the structure of xiamenmycin A has been revised [5]. As a continued program for biological research, a rapid access to all the isomers of 3-chromanol core of all the xiamenmycins is needed.…”