Abstract
A convenient four step synthesis of amino hydroxy pyrrolidines is
presented. From the readily available D- and L-tetronic acids the
four possible stereoisomeric 4-amino-3-hydroxy pyrrolidines 14,
15, 17 and 19 could be accessed as crystalline compounds, avoiding
any chromatographic purification. The key step in the reactions
was the regioselective formation of either the
2,4-diamino-2,4-dideoxy-D-threono-1,4-lactam (5) or the
3,4-diamino-3,4-dideoxy-L-erythrono-1,4-lactam (10) by treatment
of the methyl 4-bromo-4-deoxy-2,3-cis- 3 or 2,3-trans- 9 epoxy
tetronates, respectively, with liquid ammonia. Thus, opposite
regioselectivity for opening of the cis-configurated epoxide 3 (4
: 1, C-2 : C-3) and the trans-configurated epoxide 9 (3 : 7, C-2 :
C-3) by ammonia was observed. - Initial testing as glycosidase
inhibitors of the amino hydroxy pyrrolidines formed by reduction
of the lactams showed an inhibition of alfa-mannosidase (Ki 40 uM)
by isomer 14, (3R, 4S)-4-amino-3-hydroxypyrrolidine
Original language | English |
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Journal | Synthesis |
Pages (from-to) | 178-183 |
Publication status | Published - 1999 |