4-(Dimethylamino)Benzaldehyde → Castanospermine

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Reaction Steps

Australine (FIG. 1) was isolated by repeated preparative centrifugal thin-layer chromatography as a colorless oil which was crystallized from acetone with some difficulty as small, dextrorotatory prisms, m.p. 148°-149°. The moleoular formula was determined by high-resolution mass spectrometry to be C8H15NO4. The alkaloid formed a tetraacetate derivative under mild acetylation conditions indicating the presence of four primary or secondary hydroxyl groups. However, on thin layer chromatography this alkaloid gave a weak blue-gray spot with acetic anhydride-Ehrlich's spray reagent rather than the intense purple spot characteristic of polyhydroxyindolizidine alkaloids. The latter color is produced by dehydration and rearrangement to give a pyrrole ring system which undergoes condensation with the 4-dimethylaminobenzaldehyde at the position alpha- to the nitrogen atom (70). The pyrrole ring generated from australine must therefore bear a substituent blocking the alpha-position. Moreover, the electron impact mass spectrometry (EIMS) showed no ion corresponding to the six-membered ring fragment, resulting from cleavage of bonds B to the nitrogen atom in the pyrrolidine ring moiety (17), typical for castanospermine and other indolizidine alkaloids. Instead, the base peak occurred at m/z 158[M-31]+, indicating loss of an exocyclic --CH2OH group. The fundamental ring system was thus shown to be of the pyrrolizidine type. Other major fragments observed in the mass spectrum were typical for this class of compound, resulting from cleavage of either of the five-membered rings at bonds B to the nitrogen atom. The masses of these ions were such that a single --OH group had to reside on one ring while the remaining two --OH groups and the --CH2OH moiety fully substituted the alternate ring. In all saturated necine bases previously isolated, such as rosmarinecine (FIG. 3) which bear the --CH2OH group at the 1-position, the major mass spectral fragments result from cleavage of the ring system. In contrast, the major fragment from australine is a consequence of the loss of --CH2OH, indicating that this substituent must be B to the nitrogen atom at the 3-position.

Provenance & Evidence