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Synthesis of the Monodeoxy Neoglycolipid Analogues of Globotrioside; Development of Some New Methods in Carbohydrate Chemistry.

Zhang, Zhiyuan (1996)
Abstract
1. All monodeoxy TMSEt globotriosides (GbO3) and double-chain bis-sulfone GbO3-lipids were synthesised. The alpha-glycosylation with deoxygenated glycosyl donors (fluoride, ethylthio- and thiopyridin-2-yl-) was investigated in the syntheses of the TMSEt 2"-, 3",- 4"- and 6"-deoxy GbO3, and activation of the thiopyridin-2-yl-glycosides with AgOTf gave the best yield and selectivity. Glycosylation with per-benzylated galactosyl chloride and of 2'-, 3'- and 6-deoxy lactosides, under treatment with AgOTf-collidine gave the trisaccharides (37-93%). Selective removal of the protecting group at 6'-O (-TBDMS or -MBn) of GbO3, followed by iodination and reduction gave the 6'-deoxy trisaccharide. DDQ-oxidative removal and rearrangement of... (More)
1. All monodeoxy TMSEt globotriosides (GbO3) and double-chain bis-sulfone GbO3-lipids were synthesised. The alpha-glycosylation with deoxygenated glycosyl donors (fluoride, ethylthio- and thiopyridin-2-yl-) was investigated in the syntheses of the TMSEt 2"-, 3",- 4"- and 6"-deoxy GbO3, and activation of the thiopyridin-2-yl-glycosides with AgOTf gave the best yield and selectivity. Glycosylation with per-benzylated galactosyl chloride and of 2'-, 3'- and 6-deoxy lactosides, under treatment with AgOTf-collidine gave the trisaccharides (37-93%). Selective removal of the protecting group at 6'-O (-TBDMS or -MBn) of GbO3, followed by iodination and reduction gave the 6'-deoxy trisaccharide. DDQ-oxidative removal and rearrangement of p-methoxybenzylidene acetals gave the 2- and 3-deoxy- 4-OH acceptors which were glycosylated with different galabiosyl donors and promoters. Only Ag-silicate was mild enough to activate the glycosyl bromide and prevent anomerisation of the 2-deoxy glucoside to give the trisaccharide in 86% yield. NIS-AgOTf-promoted glycosylation with thiophenyl galabioside gave the 3-deoxy TMSEt trisaccharide (92%). Full deprotection gave all the water soluble monodeoxy TMSEt GbO3. Transformation of protected trisaccharides into trichloroacetimidates, via the corresponding hemiacetals, proceeded in (78-96%) overall yield (except for 2-deoxy). Glycosylation of bis-sulfone lipid alcohol with these trichloroacetimidates, proceeded in 37-79% yield, and removal of protecting groups gave the deoxy neoglycolipids. A new synthetic strategy was used in the preparation of the 2-deoxy glycolipid .



2. A method of DDQ-oxidative opening of p-methoxybenzylidene acetals was investigated. The 6-Br and 6-Cl derivatives were obtained in over 90% yield by treatment with a DDQ-halide source, whereas 4-OH-6-OMBz derivatives were obtained (~80%) by treatment with DDQ-H2O-AcOH.



3. The transformation of p-methoxyphenyl glycosides into glycosyl bromides (82-98%), glycosyl chlorides (81-99%) and phenyl thioglycosides (80-100%) was studied.



4. The migration of benzoate under dibutyltin oxide treatment gave 2-OH tri-O-Bz batha-galactosides. Furthermore, the 3-OH and 3,2'-diol per-benzoylated batha-lactosides were prepared in high yields. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Lönn, Hans, Astra Draco AB
publishing date
type
Thesis
publication status
published
subject
keywords
phenyl thioglycoside, glycosyl chloride, glycosyl bromide, 4-methoxyphenyl glycoside, 4-methoxybenzylidene acetal, 6-chlorodeoxy, 6-bromodeoxy, DDQ, 2-deoxy batha-glycoside, glycosylation, deoxy globotrioside, neoglycolipid, anomeric protection, Organic chemistry, Organisk kemi
pages
82 pages
publisher
Organic Chemistry, Lund University
defense location
Chemical Center, Lecture hall D
defense date
1996-04-11 10:15
external identifiers
  • other:ISRN: LUTKDH/(TKOK-1027)/1-82/(1996)
language
English
LU publication?
no
id
f29863b2-78af-422d-a1e5-0c60a2874d41 (old id 28326)
date added to LUP
2007-06-12 08:30:31
date last changed
2016-09-19 08:45:11
@phdthesis{f29863b2-78af-422d-a1e5-0c60a2874d41,
  abstract     = {1. All monodeoxy TMSEt globotriosides (GbO3) and double-chain bis-sulfone GbO3-lipids were synthesised. The alpha-glycosylation with deoxygenated glycosyl donors (fluoride, ethylthio- and thiopyridin-2-yl-) was investigated in the syntheses of the TMSEt 2"-, 3",- 4"- and 6"-deoxy GbO3, and activation of the thiopyridin-2-yl-glycosides with AgOTf gave the best yield and selectivity. Glycosylation with per-benzylated galactosyl chloride and of 2'-, 3'- and 6-deoxy lactosides, under treatment with AgOTf-collidine gave the trisaccharides (37-93%). Selective removal of the protecting group at 6'-O (-TBDMS or -MBn) of GbO3, followed by iodination and reduction gave the 6'-deoxy trisaccharide. DDQ-oxidative removal and rearrangement of p-methoxybenzylidene acetals gave the 2- and 3-deoxy- 4-OH acceptors which were glycosylated with different galabiosyl donors and promoters. Only Ag-silicate was mild enough to activate the glycosyl bromide and prevent anomerisation of the 2-deoxy glucoside to give the trisaccharide in 86% yield. NIS-AgOTf-promoted glycosylation with thiophenyl galabioside gave the 3-deoxy TMSEt trisaccharide (92%). Full deprotection gave all the water soluble monodeoxy TMSEt GbO3. Transformation of protected trisaccharides into trichloroacetimidates, via the corresponding hemiacetals, proceeded in (78-96%) overall yield (except for 2-deoxy). Glycosylation of bis-sulfone lipid alcohol with these trichloroacetimidates, proceeded in 37-79% yield, and removal of protecting groups gave the deoxy neoglycolipids. A new synthetic strategy was used in the preparation of the 2-deoxy glycolipid .<br/><br>
<br/><br>
2. A method of DDQ-oxidative opening of p-methoxybenzylidene acetals was investigated. The 6-Br and 6-Cl derivatives were obtained in over 90% yield by treatment with a DDQ-halide source, whereas 4-OH-6-OMBz derivatives were obtained (~80%) by treatment with DDQ-H2O-AcOH.<br/><br>
<br/><br>
3. The transformation of p-methoxyphenyl glycosides into glycosyl bromides (82-98%), glycosyl chlorides (81-99%) and phenyl thioglycosides (80-100%) was studied.<br/><br>
<br/><br>
4. The migration of benzoate under dibutyltin oxide treatment gave 2-OH tri-O-Bz batha-galactosides. Furthermore, the 3-OH and 3,2'-diol per-benzoylated batha-lactosides were prepared in high yields.},
  author       = {Zhang, Zhiyuan},
  keyword      = {phenyl thioglycoside,glycosyl chloride,glycosyl bromide,4-methoxyphenyl glycoside,4-methoxybenzylidene acetal,6-chlorodeoxy,6-bromodeoxy,DDQ,2-deoxy batha-glycoside,glycosylation,deoxy globotrioside,neoglycolipid,anomeric protection,Organic chemistry,Organisk kemi},
  language     = {eng},
  pages        = {82},
  publisher    = {Organic Chemistry, Lund University},
  title        = {Synthesis of the Monodeoxy Neoglycolipid Analogues of Globotrioside; Development of Some New Methods in Carbohydrate Chemistry.},
  year         = {1996},
}