Dihydroxyacetone Variants in the Organocatalytic Construction of Carbohydrates: Mimicking Tagatose and Fuculose Aldolases

Dihydroxyacetone variants have been explored as donors in organocatalytic aldol reactions with various
aldehyde and ketone acceptors. The protected form of dihydroxyacetone that was chosen for in-depth
study was 2,2-dimethyl-1,3-dioxan-5-one, 1. Among the catalysts surveyed here, proline proved to be
superior in terms of yield and stereoselectivities in the construction of various carbohydrate scaffolds. In
a fashion analogous to aldolase enzymes, the de novo preparation of l-ribulose, l-lyxose, d-ribose,
d-tagatose, 1-amino-1-deoxy-d-lyxitol, and other carbohydrates was accomplished via the use of 1 and
proline. In reactions using 2,2-dimethyl-1,3-dioxan-5-one 1 as a donor, (S)-proline can be used as a
functional mimic of tagatose aldolase, whereas (R)-proline can be regarded as an organocatalytic mimic
of fuculose aldolase.