Three diastereoisomeric hydroxyethylene isosters of the Val-
Ala dipeptide were synthesized from α,β-unsaturated ketones
1 derived from N-Boc- and N,N-dibenzyl-L-valine. The
enones were hydrocyanated with diethylaluminum cyanide
to give the corresponding β-cyano ketones with the stereoselectivity
depending on the protecting group. N-Boc protected
enone 1a gave a 1:1 mixture of anti and syn adducts
4a, 5a while the corresponding N,N-dibenzyl compound 1c
gave a 6:1 mixture of anti, syn adducts 4c, 5c. Borohydride
reduction of the resulting cyano ketones is also controlled by
the protecting group, resulting in opposite stereoselectivities
for N-Boc and N,N-dibenzyl compounds. The cyano alcoholsthus obtained were converted, in several steps, into two series
of enantiomerically pure hydroxyethylene isosters of the
Val-Ala dipeptide. In the first series the hydroxy group and
the N-terminal of the isoster are internally protected through
the formation of an oxazolidine; in the second series the hydroxy
group and the C-terminal are protected as lactone.
Two oxazolidines (28, 29), corresponding to syn,syn and
syn,anti 4-hydroxy-5-amino acid isosters, and three lactones
(23−25), corresponding to syn,syn, syn,anti, and anti,anti isosters
were obtained by this approach.
