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  4. Total, asymmetric synthesis of methyl 3-deoxy-3-(1 ',2 ',6 '-trideoxy-2 ',6 '-imino-D-galactitol-1-yl)-alpha-D-manno-pyranoside (A C-linked imino disaccharide): Conformational analysis and glycosidase inhibition
 
research article

Total, asymmetric synthesis of methyl 3-deoxy-3-(1 ',2 ',6 '-trideoxy-2 ',6 '-imino-D-galactitol-1-yl)-alpha-D-manno-pyranoside (A C-linked imino disaccharide): Conformational analysis and glycosidase inhibition

Marquis, C.
•
Picasso, S.
•
Vogel, P.  
1999
Synthesis: Journal of Synthetic Organic Chemistry

The lithium enolate 16 derived in 5 steps from the Diels-Alder adduct of furan to 1-cyanovinyl (1S)-camphanate [(+)-12: a "naked sugar" of the first generation] was reacted with (+)(1R,4S,5S,6S)-6-endo-chroro-3-methylidene-5-exo-phenylseleno-7-oxabic yclo[2.2.1]. heptan-2-one [(+)-8] to give a unique product of Michael addition after acidic quenching. This adduct (-)-18 was transformed into branched long-chain carbohydrate derivatives such as benzyl 5-deoxy-5-[(5"-O-acetyl-3"-deoxy-2"-O-methoxymethyl-D-manno-furanurono-6 , 1-lactone-3''-yl)methyl]- (tert-butyl)dimethylsilyl-2,3-di-O-methoxymethyl-alpha and beta-L-gulo-furanosideuronate [(-)-27]. Hydrogenolysis, followed by a Curtius rearrangement permitted to construct the corresponding branched 5-amino-5,6-dideoxydodecose derivative (-)-30 which was converted into 5-O-acetyl-3- [ 5'-N-(benzyloxy)carbonyl-2',3'-di-O-methoxymethyl-alpha and beta-D-manno-furanose]-2-O-methoxymethyl-D-manno-furanurono-6, 1-lactone [(-)-31] and then into methyl 3-deoxy-3-(1',2',6'-trideoxy-2',6'-imino-D-galactitol-1'-yl)-alpha-D-man no-pyranoside [(-)-1]. Its H-1 NMR spectrum measured at variable temperature demonstrated that (-)-1 exist as a double equilibrium involving two pairs of rotamers about the sigma C(1')-C(2') and sigma C(1')-C(3) bond [CH2 bridge linking beta-C(I) of the I,5-dideoxy-1,5-imino-D-lyxitol unit at C(3) of methyl alpha-D-manno-pyranoside]. Rotamers B' in which C(3) is gauche with respect to C(3') is preferred to conformers C' in which C(3) is anti with respect to C(3'). An equilibrium constant K (B' = C') congruent to 0.35 (25 degrees C) was evaluated. Rotamers B [C(2) gauche with respect to C(2')] and C [C(2) anti with respect to C(2')] are equally populated. Disaccharide mimetic (-)-1 is a moderate inhibitor of alpha-L-fucosidases from bovine liver (K-i = 100 mu M) and human placenta.

  • Details
  • Metrics
Type
research article
DOI
10.1055/s-1999-3645
Author(s)
Marquis, C.
Picasso, S.
Vogel, P.  
Date Issued

1999

Publisher

Georg Thieme Verlag

Published in
Synthesis: Journal of Synthetic Organic Chemistry
Issue

Sup. 1

Start page

1441

End page

1452

Subjects

5-amino-5

•

6-dideoxydodecose

•

branched long-chain carbohydrates

•

alpha-L-fucosidase inhibitor

•

van't Hoff plot for rotamers

•

"naked

•

sugars"

•

C-glycosides

•

trihydroxypiperidine

•

7-oxabicyclo[2.2.1]heptyl

•

derivatives

•

Influenza neuraminidase inhibitors

•

immunodeficiency virus type-1

•

derivatives naked sugars

•

alpha-l-fucosidase

•

preferred conformation

•

envelope glycoproteins

•

oligosaccharides

•

azasugars

•

analogs

•

design

Note

Univ Lausanne, Chim Sect, BCH, CH-1015 Lausanne, Switzerland. Calbiochem Novabiochem AG, CH-4448 Laufelfingen, Switzerland.

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LGSA  
Available on Infoscience
November 9, 2005
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/219751
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