N-Substituted (3S,4S)-and (3R,4R)-pyrrolidine-3,4-diols 9 and 10, respectively, were derived from ()-land (À)-d-tartaric acid, respectively. Compounds 9k, 9l, and 9m with the N-substituents, BnNH(CH 2 ) 2 , 4-PhC 6 H 4 CH 2 NH(CH 2 ) 2 and 4-ClC 6 H 4 CH 2 NH(CH 2 ) 2 , respectively, showed modest inhibitory activities toward ad-amyloglucosidases from Aspergillus niger and from Rhizopus mold (Table 1). Unexpectedly, several (3R,4R)pyrrolidine-3,4-diols 10 showed inhibitory activities toward a-d-mannosidases from almonds and from jack bean (Table 3). N-Substitution by the NH 2 (CH 2 ) 2 group, i.e., 10g, led to the highest potency. 1 ) Compound 9f was also obtained from ()-l-tartaric acid and butanamine via (3R,4R)-1-butyl-3,4dihydroxypyrrolidine-2,5-dione (see Exper. Part) and LiAlH 4 reduction of the latter (yield 28% over two steps; not shown). Scheme 2. Synthesis of N-Alkylated Derivatives 9d ± f the dihydroxy bis-tosylate 18 (obtained from (R,R)-11 via 16 and 17 [21] [22]
) with the corresponding primary amines (Scheme 3). Unfortunately, yields were even poorer than those observed with reactions of Scheme 2.
The known dibenzyloxy bis-ditosylate 19 [23] reacted with propanamine and butanamine giving pyrrolidine-3,4-diols 20e (92%) and 20f (92%), respectively. Subsequent hydrogenolysis (H 2 , Pd(OH) 2 /C, MeOH, AcOEt) afforded 9e (82%) and 9f (82%), respectively (Scheme 3). With diamines H 2 N(CH 2 ) 2 NH 2 , H 2 N(CH 2 ) 2 NHEt, H 2 N(CH 2 ) 2 NMe 2 , and H 2 N(CH 2 ) 3 NH 2 , bis-tosylate 19 yielded the corresponding pyrrolidine-3,4-diols 20g ± j that were debenzylated to the corresponding N-substituted (3S,4S)-pyrrolidine-3,4-diols 9g ± j in good yields. (Aminoethyl)pyrrolidinediol 9g was also obtained by amidification of (2R,3R)-2,3-di-O-benzyltartaric acid [24] with H 2 N(CH 2 ) 2 NH 2 [25]. Amide reduction with LiAlH 4 (26%) and subsequent debenzylation (89%) under standard conditions produced 9g.
Reductive amination of benzaldehyde ( 21), [1,1'-biphenyl]-4-carboxaldehyde ( 22), and 4-chlorobenzaldehyde ( 23) with (aminoethyl)pyrrolidinediol 9g (MeOH, 208; then NaBH(OAc) 3 ) [16] provided pyrrolidine-3,4-diols 9k (73%), 9l (73%), and 9m (77%), respectively. Similarly, reductive amination of benzaldehyde ( 21) with (aminopropyl)pyrrolidinediol 9j gave pyrrolidine-3,4-diol 9n (42%) (Scheme 4).