Orevactaene,1 a novel binding inhibitor of HIV-1 rev protein to Rev response element (RRE) from Epicoccum nigrum WC47880

Polyunsaturated C‐Glycosidic 4‐Hydroxy‐2‐pyrone Derivatives: Total Synthesis Shows that Putative Orevactaene Is Likely Identical with Epipyrone A

“…[1] Rather,a ll evidence suggests that orevactaene is identical with epipyrone A. As will become evident below,itisthe spectroscopic fingerprint of uniformly large 3 J couplings between H3, H4, and H5 that confirmed that orevactaene cannot contain an annulated backbone as originally proposed.…”

“…[1] Thed ifferences in the 13 CNMR spectra were no less striking.T he maximum shift differences were noted for C3 (12.0 ppm) and C33 (9.2 ppm), which can hardly be explained by stereochemical arguments.T he spectra of isomer (S,R)-1 ( Figure 1) were not matching any better, which confirms that the configuration of the distal stereocluster in the tail region does not have asignificant impact on the spectral features of the head group held apart by the stiff polyene chain. The 1 HNMR shifts were largely off,a nd the 3 J couplings for the protons H3, H4, and H5 were all in the range of 3-4 Hz rather than > 9Hza s reported for 1.…”

“…Under the premise that the 2-pyrone ring and the sugar segment might not be annulated as originally proposed, [1] it seems plausible that …”

“…Orevactaene (1,a lso called BMS-213438) [1] and epipyrone A( 2,a lso called D8646-2-6) [2,3] are the most noteworthy representatives of an exceedingly rare chemotype comprising a4 -hydroxy-2-pyrone nucleus decorated with aC -glycosidic substituent and ap olyunsaturated side chain (Scheme 1). [4] Both compounds were isolated from Epicoccum purpurascens (syn.…”

“…[4] Both compounds were isolated from Epicoccum purpurascens (syn. E. nigrum)strains;whereas 1 exhibits HIV-1 inhibitory properties, [1] 2 and congeners were originally described as telomerase inhibitors; [2] later on, 2 was found to show significant activity against the influenza Avirus (H1N1) and was also patented for use as af ungicide. [3,5] While these intriguing natural products seem to share an identical conjugated heptaene tail terminated by adimethyl-branched pentyl chain of as yet unknown configuration, they ostensibly differ in their signature head groups: 2 features aregular b-Cglycosidic link between a4 -hydroxy-2-pyrone and ag alactopyranosyl ring, whereas the pyrone and the carbohydrate part in 1 are thought to be annulated.…”