| 摘要 |
Prodn. of 2-(3S-amino-2R-hydroxy-4-phenylbutyl)-N-t-butyl- decahydro-(4aS,8aS)-isoquinoline-3S-carboxamide of formula (I) comprises (a) reacting a L-phenylalanine lower alkyl ester (A) with ClCOOR1 to give a (S) diester of formula R1OCONHCH(Bz)COOR (II); (b) reacting (II) with a halomethyl lithium cpd. to give a halomethyl ketone of formula R1OCONHCH(Bz)COCH2X (III); (c) reducing (III) to an (S,S) alcohol of formula R1OCONHCH(Bz)CHOHCH2X (IV); (d) cyclising (IV) with a base to give an (S,S) oxirane deriv. of formula R1OCONHCH(Bz)A (V); (e) reacting (V) with N-t-butyl-decahydro-(4aS,8aS)-isoquinoline-3S-carboxamide (VI); and (f) treating the prod. of formula (VII) with a base. R1 = lower alkyl, Bz or phenyl; Bz = benzyl; R = lower alkyl; X = halogen; A = 2-oxiranyl. Also claimed is the prodn. of (III) by reacting (II) with a lower alkyl lithium cpd. and an organochlorosilane to form a silyl-protected intermediate, and reacting this with a dihalomethane and a lower alkyl lithium cpd. The cpds. (III)-(VII), all with R1 = Me; X = Cl are new. |
