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-methyl-muconodilactone

Abstract

(±)-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.