87729-23-5Relevant academic research and scientific papers
Synthesis of Epoxytrichothecenes: Verrucarin J and Verrucarin J Isomers
Roush, William R.,Blizzard, Timothy A.
, p. 1772 - 1783 (2007/10/02)
A five-step synthesis of verrucarin J (1) from verrucarol (2) is described.Esterification of (E)-21 and 2 with DDC in the presence of catalytic DMAP was highly regioselective but afforded a 3-4:1 mixture of (E)-23 and the corresponding Z olefin isomer.Two routes from (E)-23 to seco acid 13 are described, the most efficient of which involves the coupling of (E)-24 ("verrol") with muconate ester 28.Macrolactonization of seco acid 13 via mixed anhydride 31 afforded 55-60percent of 1 together with 25-30percent of E,E,E isomer 32.Although attempts to suppress the formation of 32were unsuccessful, treatment of 32 with I2 in C6H6 effected clean isomerization to a 2:1 mixture of 1 and E,Z,E isomer 33.The overall yield of verrucarin J from verrucarol, after a recycle of 32, was 27-30percent .Also described are syntheses of (Z,E,Z)-verrucarin (40) and Z,E,E isomer 41.Verrucarins 1 and 40 are nearly equipotent in the in vitro L1210 mouse leukemia assay, but the (E,E)-muconate isomers 32 and 41 are less active by an order of magnitude.These data may reflect the solvolytic reactivity of 32 and 41, since these compounds rapidly transesterify in EtOH.Seco acid 13 was essentially inactive in the L1210 assay.
Rotational Selectivity in Cyclobutene Ring Openings. Model Studies Directed toward a Synthesis of Verrucarin A
Trost, Barry M.,McDougal, Patrick G.
, p. 458 - 468 (2007/10/02)
The rotational selectivity in the opening of dissymmetric cyclobutenes to the corresponding dienes is described.In the opening of the monoesters of cis-3,4-cyclobutenedicarboxylic acid, an unusual solvent effect on the ring opening is noted.Switching from Me2SO to 1,2-dichloroethane leads to a 3:1 ratio of the (E,Z)-muconates, favoring the ester on the E double bond.The two isomers can be differentiated by 13C NMR spectroscopy in which the above isomer shows a Δδ for the α,α' carbons of only ca. 2.5 ppm but a Δδ of 5-6 ppm for the isomer having the ester on theZ double bond.Inclusion of the cyclobutene as part of a macrotriolide related to verrucarin A imparts conformational control on the rotational selectivity to favor the E,Z isomer corresponding to the natural products.These relatively simple models inhibit protein synthesis in a fashion reminiscent of the natural products.
