Helvetica Chimica Acta p. 3991 - 3999 (2003)
Update date:2022-08-05
Topics:
Darley, Dan J.
Selmer, Thorsten
Clegg, William
Harrington, Ross W.
Buckel, Wolfgang
Golding, Bernard T.
2-Methylisocitrate (=3-hydroxybutane-1,2,3-tricarboxylic acid) is an intermediate in the oxidation of propanoate to pyruvate (=2-oxopropanoate) via the methylcitrate cycle in both bacteria and fungi (Scheme 1). Stereocontrolled syntheses of (2R,3S)- and (2S,3R)-2-methylisocitrate (98% e.e.) were achieved starting from (R)- and (S)-lactic acid (=(2R)- and (2S)-2-hydroxypropanoic acid), respectively. The dispiroketal (6S,7S,15R)-15-methyl-1,8,13,16-tetraoxadispiro[5.0.5.4]hexadecan-14-one (2a) derived from (R)-lactic acid was deprotonated with lithium diisopropylamide to give a carbanion that was condensed with diethyl fumarate (Scheme 3). The configuration of the adduct diethyl (2S)-2-[(6S,7S,14R)-14-methyl-15-oxo-1,8,13,16-tetraoxadispiro[5.0.5.4] hexadec-14-yl]butanedioate (3a) was assigned by consideration of possible transition states for the fumarate condensation (cf. Scheme 2), and this was confirmed by a crystal-structure analysis. The adduct was subjected to acid hydrolysis to afford the lactone 4a of (2R,3S)-2-methylisocitrate and hence (2R,3S)-2-methylisocitrate. Similarly, (S)-lactic acid led to (2S,3R)-2-methylisocitrate. Comparison of 2-methylisocitrate produced enzymatically with the synthetic enantiomers established that the biologically active isomer is (2R,3S)-2-methylisocitrate.
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Doi:10.1007/BF00909671
(1980)Doi:10.1002/pola.26062
(2012)Doi:10.1016/j.bmc.2004.07.010
(2004)Doi:10.1016/0022-1902(80)80280-6
(1980)Doi:10.1016/S0040-4039(00)78758-2
(1980)Doi:10.1016/S0008-6215(00)84673-X
(1980)