Ammonia lactone group reaction with

Reaction of the Lactone Group with Ammonia and Amines... 

An example of a condensation reaction with diastereotopic group selectivity (see appendix) is the lactonization of either of the two racemic, C2-symmetrical 5-hydroxy-2,4,6,8-tetramethylnonanedioic acids. This reaction desymmetrizes a compound with two pairs of equivalent stereocenters (C-5 is achiral ) into a product with five different stereocenters. The trilithium salt is generated by reduction of the 2,4,6,8-tetramethyl-5-oxononanedioic acid with lithium in ammonia and then either acidified to pH 3 followed by rapid extraction of the lactones formed (kinetic control) or equilibrated at pH w 1 to the lactone mixture (thermodynamic control). Depending on the steric interactions in the chair-like transition states and in the half-chair lactone products, either kinetic or thermodynamic control leads with high diastereoselectivity to the lactone with trans-configuration at C-5 and C-6 of the tetra-hydro-2/f-pyran-2-one ring (T. R. Hoye, 1984). 

In an interesting reaction, -santonin was reduced with lithium in liquid ammonia so that the lactone was hydrogenolyzed to an add and one of the double bonds conjugated with the carbonyl was reduced. The other double bond as well as the keto group did not undergo reduction [1091]. 

The question then arises if a regioselective opening of a 2,3-rraMS-epoxy carboxamide derived from aldonic acids would occur. The 2,5-di-O-tosyl-D-ribono-1,4-lactone (62) (Scheme 13) was used to find an answer to this question. If treated with ammonia, the 2,5-diamino-2,5-dideoxy-D-ribono-1,5-lactam (63) was obtained as the only product [79]. The NMR spectra of the reaction mixture showed the formation of the diepoxy amide A which was opened at C-5 by ammonia. In this case no internal lactamization could occur, due to the trans 2,3-epoxy group in B (Scheme 13). Thus, a regioselective opening of an acyclic 2,3-epoxy carboxamide took place at C-2. The reaction was complete within 6 days. 

The reaction of the methyl ester of the racemic epoxide 101 with acetone and aluminum chloride gave a 4,S-0-isopropylidene derivative 108. Michael addition of ammonia to the conjugated double bond of 108 with concomitant ammonolysis of the ester group afforded a mixture of 3-amino-2,3,6-trideoxy-4,5-0-isopro-pylidene-OL-arabino- and -r/Z o-hexonamides (109). For the purpose of isolation the mixture was N-acetylated. Acidic hydrolysis of the amide groupings gave a mixture of y- and 8-aminolactone hydrochlorides (110 and 111). Careful N-acetylation and reduction of the lactone carbonyl groups in 112 and 113 afforded N-acetyl-DL-acosamine (115) in 36% yield. The stereoisomeric potential partner of 115, N-acetyl-DL-ristosamine (116), was not isolated in this procedure. 

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