Synthesis and absolute configurations of the naturally occurring 3- and 4-methylmuconolactones: X-ray structures of (S)-1-phenylethylammonium salts and an 8-bromo-1-methylmuconodilactone

(+/-)-3-Methylmuconolactone (+/-)-4 is resolved by fractional crystallisation of the (S)-(-)-1-phenylethylammonium salts. The X-ray crystal structures of both salts are determined. Salt A (Fig, 1) gives (S)-(-)-3-methylmuconolactone 4, which is identical to the lactone from fungi, The lactone is converted with bromine into the bromo dilactone 5 and thence with tributyltin hydride into the (-)-1-methylmuconodilactone 6. This dilactone with aqueous sodium hydroxide gives (S)-(+)-4-methylmuconolactone 3, which is identical to the lactone from bacteria, together with (S)-(-)-3-methylmuconolactone 4, The X-ray structure of the bromo dilactone 5 (Fig, 3) confirms the absolute configurations of both the fungal and bacterial muconolactones, (S)-(+)-4-Methylmuconolactone 3 gives the corresponding (-)-bromo dilactone 9, which is also reduced with tributyltin hydride to yield the (-)-1-methylmuconodilactone 6. The isomeric bromo dilactones (+/-)-5 and 9 are similarly converted into the dibromo dilactones (+/-)-8 and 11 via the corresponding 2-bromomuconolactones (+/-)-7 and 10, respectively. Disodium 3-methyl-cis,cis-muconate 17 is prepared non-enzymically by treatment of 3-methylmuconic anhydride 16 with 2 mol equiv, of aqueous sodium hydroxide, Unexpectedly, the salt 17 rapidly gives 3-methyl-2-cis,4-trans-muconate even in weakly alkaline solutions, Contrary to an earlier report, at pD 6.5 the salt 17 is converted at approximately equal rates into 3-methyl-2-cis,4-trans-muconic acid 18 and (+/-)-3-methylmuconolactone (+/-)-4.