First efficient synthesis of (±)-erythro-roccellic acid†

A new route to (±)-erythro-roccellic acid and chaetomellic anhydride C through functional rearrangement, promoted by n-propylamine or CH3ONa/CH3OH, of N-propyl-3-chloro-4-dichloromethyl-3-dodecylpyrrolidin-2-one

“…19 involved the elaboration of related heterocycles (Scheme 1). 9 This work, using precursors such as the maleimide 2 and/or the maleic anhydride 3, showed that catalytic hydrogenation could be used to produce the observed relative configuration of the C(2) and C(3) carbons in acid 1 (Scheme 1). 9,18 Our approach to the pyrrolin-2,5-dione nucleus starts with the pivotal functional rearrangement (FR) of an appropriate 4-methyl-pyrrolidin-2-one (A), which has at least three chlorine atoms at the C(3) and C(6) positions.…”

“…9 This work, using precursors such as the maleimide 2 and/or the maleic anhydride 3, showed that catalytic hydrogenation could be used to produce the observed relative configuration of the C(2) and C(3) carbons in acid 1 (Scheme 1). 9,18 Our approach to the pyrrolin-2,5-dione nucleus starts with the pivotal functional rearrangement (FR) of an appropriate 4-methyl-pyrrolidin-2-one (A), which has at least three chlorine atoms at the C(3) and C(6) positions. These compounds, when treated with a solution of alkaline methoxide (in methanol under mild conditions), are converted into the corresponding 5,5-dimethoxy-4-methyl-3-pyrrolin-2-ones (B) (Scheme 2).…”

“…Owing to the remarkable biological activity of 1, there is a need for the development of more effective methods for preparing 1 and this is an area of current interest. 9 Recently, Argade and Mangaleswaran have developed an efficient route to (G)-erythro-roccellic acid 1 starting from N-(p-tolyl)citraconimide. 9 Also, Fensterbank and Malacria have exploited the conjugate addition of the lithium enolate of 2,6-dimethylphenyl propanoate to a chiral undecylidene bis(sulfoxide), in an enantioselective synthesis of (C)-erythro-roccellic acid 1, although the yield was low.…”

“…9 Recently, Argade and Mangaleswaran have developed an efficient route to (G)-erythro-roccellic acid 1 starting from N-(p-tolyl)citraconimide. 9 Also, Fensterbank and Malacria have exploited the conjugate addition of the lithium enolate of 2,6-dimethylphenyl propanoate to a chiral undecylidene bis(sulfoxide), in an enantioselective synthesis of (C)-erythro-roccellic acid 1, although the yield was low. 19 involved the elaboration of related heterocycles (Scheme 1).…”

“…[3][4][5] This compound was isolated by von Heeren from Roccella fuciformis and Roccella tinctoria 2 and has since been observed in many other lichens. 2,[6][7][8][9] It is a remarkably interesting natural product owing to its numerous synthetic uses and biological properties. This dibasic fatty acid has been used in the preparation of actinonin antibiotic analogues, 10 in the precipitation of human serum albumin 11 and in the assembly of metal complexes.…”