Total Enantioselective Synthesis of the Endophytic Fungal Polyketide Phomolide H and Its Structural Revision

Abstract

A total synthesis of the proposed structure of the natural polyketide‐macrolactone phomolide H 2 has been achieved following a bidirectional strategy from l‐tartaric acid. The originally assigned structure of phomolide H displayed discordant NMR spectroscopic data in comparison with synthetic 2. The synthetic strategy was extended to prepare diastereomers and epimeric methyl‐ethers of the natural product, structural analysis of which revealed a match of the natural product with diastereomer 27. The structural revision of phomolide H from 2 to the methanol solvate of compound 27 is presented.

The Synthesis of 3-(R)- and 3-(S)-Hydroxyeicosapentaenoic Acid

“…The crude product was purified by column chromatography (hexane/EtOAc 9:1) to afford the chiral auxiliary 5b (1.70 g) as a bright yellow oil in a 90% yield. All spectroscopic and physical data were in agreement with those reported in the literature [ 37 ]. R f = 0.23 (hexanes/EtOAc 9:1 KMnO 4 stain); 1 H NMR (400 MHz, CDCl 3 ) δ 5.14 (ddd, J = 7.7, 6.1, 1.2 Hz, 1H), 3.50 (dd, J = 11.5, 8.1 Hz, 1H), 3.01 (dd, J = 11.5, 1.2 Hz, 1H), 2.76 (s, 3H), 2.41–2.31 (m, 1H), 1.05 (d, J = 6.8 Hz, 3H), 0.96 (d, J = 7.0 Hz, 3H).…”

Pitfalls in the structural elucidation of small molecules. A critical analysis of a decade of structural misassignments of marine natural products

“…14). 94 On the other hand, the signicant deviation between the reported quasi-molecular ion peak at m/z 281.1532 ([M + Na] + ) and the calculated value (281.1365) suggested a different formula.…”

Natural ten-membered lactones: sources, structural diversity, biological activity, and intriguing future

“…18 It is notable that stagochromene A isolated along with stagonolides A, J, and K from S. cirsii 15 has a similar skeleton and can also be a congener of TMLs. Natural product 21 as well as phomolides D-H (22)(23)(24)(25)(26) were isolated from different endophytic strains of Phomopsis sp. Compound 21 showed phytotoxic activity on germination and radicle growth of Medicago sativa, Trifolium hybridum, and Buchloe dactyloides with IC 50 values for germination 15.8, 24.2, and 31.2 mg mL −1 , and for radicle growth 31.9, 63.3, 130.9 mg mL −1 , respectively.…”

“…Compound 21 showed phytotoxic activity on germination and radicle growth of Medicago sativa, Trifolium hybridum, and Buchloe dactyloides with IC 50 values for germination 15.8, 24.2, and 31.2 mg mL −1 , and for radicle growth 31.9, 63.3, 130.9 mg mL −1 , respectively. 19 Phomolides D-H (22)(23)(24)(25)(26) had no effects on the growth of E. coli, B. subtilis, B. pumilus, S. aureus, and C. albicans at 30 mg per plate using the Oxford plate assay system. 20 The absolute congurations of phomolides G and H were revised by , and McNulty and McLeod (2017) using enantioselective total synthesis (Fig.…”