The Changing Faces of Halogenated Marine Natural Products: Total Synthesis of the Reported Structures of Elatenyne and an Enyne from Laurencia majuscula

Abstract

Knocking them into shape: The total synthesis of two reported marine natural products containing halogenated pyrano[3,2‐b]pyrans (see example in blue) has led to the reassignment of both structures as halogenated 2,2′‐bifuranyls (red). Concomitantly an efficient route to pyrano[3,2‐b]pyrans is described.

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

“…Several cases of an exocyclic olefin on a 5-membered ring as opposed to a 6-membered ring with endocyclic bond are evident in Table 1, for example, chloroaurone, 10, 11 aspergiones A and B, 12–14 pyrostatins A and B, 15, 16 and spongotine B. 17, 18 Another problematic theme is differentiation of fused 6-membered rings from two 5-membered rings linked by a single bond, as seen in the examples of the red algal metabolites laurendecumenyne B, 19, 20 elatenyne 21, 22 and Laurencia enyne. 22, 23 In these three compounds, the observed 13 C NMR shifts of the oxygen-bearing carbons were more consistent with a 2,2′-bifuranyl moiety (> 76 ppm) than the proposed pyrano[3,2- b ]pyran (< 76 ppm).…”

Production of Induced Secondary Metabolites by a Co-Culture of Sponge-Associated Actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163

“…In this work, an insufficient amount of the compound has been isolated to provide a good quality crystal for an X-ray, and the assignment was based on NMR data. However, in contrast to [2,2′]bifuranyl-pyranopyran models [41], the 13 C chemical shifts of the ring fusion atoms in 13a and 13b do not provide the distinction of the ring size [42]. Based on the literature evidence of compound 13a being the major isomer in solution [43], we propose the structure of the induced natural product to be 5a,6,11a,12-tetrahydro-5a,11a-dimethyl[1,4]benzoxazino[3,2- b ][1,4]benzoxazine ( 13a ).…”

Computer-Guided Total Synthesis of Natural Products. Recent Examples and Future Perspectives

“…For two decades, the structure of elatenyne remained unchallenged, until Burton and co-workers 57 revised it by total synthesis. As depicted in Scheme 11, one of the key steps in their synthetic approach was the generation of the pyrano[3,2-b]pyran system 96 from the thermodynamically favored rearrangement of the corresponding 2,2'-bifuranyl compound 95a.…”

“…However, they could not unequivocally determine the relative configuration of the natural product. 57 To settle this issue, Burton and co-workers established a collaboration with Goodman and co-workers to computationally unravel the most likely tridimensional structure of elatenyne. 58 From NMR calculations at the affordable B3LYP/6-31G**//MMFF level of theory, in one of the most exquisitely discussed papers in the pre-DP4 era, the authors compared the correlation coefficients and the averaged and maximum errors computed for the 32 possible diastereoisomers (including different approaches to deal with the large errors computed for the bromine- containing carbons) and concluded that structure 99 was the most likely candidate (Figure 23).…”

“…However, they finally opted for the 2,2'-bisfuran system based on the relative downfield chemical shift of C-9 and C-10 (d C > 76 ppm), considerably shifted upfield in the case of pyrano[3,2-b]pyran analogues. 57 The relative configuration of 128 was determined from NOESY experiments, revealing that protons H-6, H-7 and H-9 were syn to H-8a, whereas H-10, H-12 and H-13 were syn to H-11a. On the other hand, the connection between both tetrahydrofuran fragments could not be irrefutably assigned, and two possible stereoisomers were taken into consideration (9,10-syn and 9,10-anti).…”