Helvetica Chimica Acta p. 193 - 232 (2000)
Update date:2022-08-03
Topics:
Schaller, Christophe
Vogel, Pierre
The cross-aldolization of (-)-(1S,4R,5R,6R)-6-endo-chloro-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]hep-tan- 2-one ((-)-25) and of (+)-(3aR,4aR,7aR,7bS)-((+)-26) and (-)-(3aS,4aS,7aS,7bA)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5] furo[2,3-d]isoxazole-3-carbaldehyde ((-)-26) was studied for the lithium enolate of (-)-25 and for its trimethylsilyl ether (-)-31 under Mukaiyama's conditions (Scheme 2). Protocols were found for highly diastereoselective condensation giving the four possible aldols (+)-27 ('anti'), (+)-28 ('syn'), 29 ('anti'), and (-)-30 ('syn') resulting from the exclusive exo-face reaction of the bicyclic lithium enolate of (-)-25 and bicyclic silyl ether (-)-31. Steric factors can explain the selectivities observed. Aldols (+)-27, (+)-28, 29, and (-)-30 were converted stereoselectively to (+)-1,4-anhydro-3-{(S)-[(tert-butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a, 7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]-furo[2,3-d]isoxazol-3-yl]methyl}- 3-deoxy-2,6-di-O-(methoxymethyl)-α-D-galactopyranose ((+)-62), its epimer at the exocyclic position (+)-70, (-)-1,4-anhydro-3-{(5)-[(tert-butyl)dimethylsilyloxy][(3a5,4a5,7a5,7bR)-3a,4a, 7a,7b-tetrahydro-6,6-dimethyl[1,3]-dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}- 3-deoxy-2,6-di-O-(methoxymethyl)-α-D-galactopyranose ((-)-77), and its epimer at the exocyclic position (+)-84, respectively (Schemes 3 and 5). Compounds (+)-62, (-)-77, and (+)-84 were transformed to (1R,2R,3S,7R,8S,9S,9a5)-1,3,4,6,7,8,9,9a-octahydro-8-[(1R,2R)-1,2,3- trihydroxypropyl]-2H-quinolizine-1,2,3,7,9-pentol (21), its (1S,2S,3R,7R,8S,9S,9aR) stereoisomer (-)-22, and to its (1S,2S,3R,7R,8S,9R,9aR) stereoisomer (+)-23, respectively (Schemes 6 and 7). The polyhydroxylated quinolizidines (-)-22 and (+)-23 adopt 'trans-azadecalin' structures with chair/chair conformations in which H-C(9a) occupies an axial position anti-periplanar to the amine lone electron pair. Quinolizidines 21, (-)-22, and (+)-23 were tested for their inhibitory activities toward 25 commercially available glycohydrolases. Compound 21 is a weak inhibitor of β-galactosidase from jack bean, of amyloglucosidase from Aspergillus niger, and of β-glucosidase from Caldocellum saccharolyticum. Stereoisomers (-)-22 and (+)-23 are weak but more selective inhibitors of β-galactosidase from jack bean.
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