The Synthesis Of Several Carbohydrate Derivatives With Bioactivity

The synthesis and modification of natural sugar-derived products that have biological activity is one of the most important aspects of carbohydrate chemistry.In this thesis,the application of glucono-1,5-lactone in the synthesis of carbohydrate derivatives was described. The overall article consists of the synthesis of glycosidase inhibitor voglibose,biomaterial monomer tetraethyl glucono-1,6-lactone,azasugars and destomycin B fragment.Moreover, aromatic carboxylic acid existed in natural sugar esters was prepared in the end.1.2,3,4,6-Tetrabenzyl glucose(2)was prepared in two routes.The first route is the benzylation of methyl glucoside followed by hydrolyzing in acid solution to afford 2.Further more,the remanent acid solution was used repeatly and the yield is 50%in two steps. Compound 2 was also prepared from the hydrolyzation of octabenzyl sucrose which was got from bezylation of sucrose octaacetate with a yield of 81%.Improved method for the acetylation of carbohydrate was developed.11 kinds of sugars were acetylated quickly by using HClO₄/SiO₂ as activator;the purification process was simplified to increase reaction efficiency.This method has the feature of short reaction time,high efficiency and environmental friendly.Oxidation of 2 with DMSO and Ac₂O afforded 2,3,4,6-tetrabenzyl glucono-1,5-lactone(1).2.By utilizing 1 as a raw material,spiro ortho ester sugar was synthesized from the reaction of 1 with dimethyl propanediol in the presence of TMSOMe and TMSOTf.The reaction of resulting product with AlMe₃ to extend carbon chain was conducted.The second hydroxyl of obtained compound was oxidation with DMSO,and the residue was activated by ZnCl₂ to produce Valiolone with a yield of 35%in four steps.Reductive amination of Valiolone with L-serinol was finished by NaBH₃CN and the product was hydrogenated in the presence of Pd/C to afford target compound-Voglibose at last.The total synthetic route of voglibose has the properties of mild reaction condition,higher yield and simple purification process.3.The concise synthesis of tetraethylglucono-1,6-lactone(29)from glucono-1,5-lactone was described.Firstly,protection of 6-hydroxyl of raw compound was achieved by TrCl. Then hydrolysis of resulting compound in KOH solution was conducted.To a solution of gluconic salt,NaH and EtBr were added to protect the hydroxyl and carboxylic group and the product was heated in aqueous acetic acid to remove Tr group,ethyl tetraethyl gluconate(26) was got.Then tetraethyl gluconic acid(28)was prepared from hydrolysis of compound 26 in KOH solution then acidified by HCl.In the end,dehydration of compound 28 by DCC and DMAP resulted 29.The synthesis route was optimized.In the process of ethylating,excess NaH was added,ester bond of compound 26 was destroyed in alkaline solution,deprotection of 6-OH of resulting compound furnished compound 28.As a result,a one-pot reaction containing protection of hydroxyl and deprotection of carboxyl was developed and purification process was also simplified.4.The synthesis of azasugar was studied.2-Oxo-tetraethoxyazepane was synthesized from D-glucono-1,5-lactone.First of all,by employing 26 and 28 as raw materials,6-OH was converted to N₃ group by utilizing TsCl and NaN₃.Reduction of azide group by Ph₃P to give lactam was completed in the end.Moreover,the condition of reduction was investigated and Ph₃P was found be a high performance reagent(over 90%)for the reductive 1,6-cyclization of azide and ester with mild condition(THF/H₂O,r.t.).Furthermore,the synthesis of Miglitol was explored.Compound 1 was reacted with amino ethanol to produce gluconamide,the latter compound was treated firstly with TrCl then DMSO,Ac₂O,the key intermediate was obtained.However,the process of cyclization was failed in the presence of NaCNBH₃.5.The synthesis of Destomycin B fragment and spiro ortho ester sugar was investigated. Firstly,methyl 2,3,4-tribenzylglucoside(42)was obtained in two steps from selective debenzylation of methyl 2,3,4,6-tetrabenzylglucoside with ZnCl₂ and Ac₂O.Later,methyl 2,3,4-tribenzyl-6-deoxy-iodo-glucoside was prepared from 42 in two methods.Methyl 2,3,4-tribenzyl-6-deoxy-nitro-glucoside was got from the reaction of iodosugar with sodium nitrite.Henry reaction of nitro sugar with formaldehyde was conducted.The structure of two isomers of product was confirmed by NMR.Reduction of nitro group afforded target compound-destomycin B fragment.Secondly,Swern oxidation of compound 42 to produce hexodialdehyde was made and the resulting comnpound was reacted with nitro methane to obatain destomycin B fragment derivatives.In conclusion,the extendation of carbon chain by means of henry reaction has the feature of mild reaction condition and low cost.At last,spiro ortho ester monosaccharide and disacchadde was prepared from 1.6.The preparation of aromatic carboxylic acid derived from natural sugar ester was studied. A novel method for the synthesis of 2,2',4,4'-tetra carboxylic acid biphenyl by using p-methyl aniline as raw material was developed.Firstly,2-amino-5-methylbenzoic acid(59) was prepared from p-methyl aniline.Then,4,4'-dimethyl-2,2'-diphenylic acid was obtained by coupling of diazonium which was made from diazotization of 59.At last,the target product was prepared from the oxidation of 4,4'-dimethyl-2,2'-diphenylic acid by KMnO₄ in a alkalescent solution.The processing was optimized and the quantity of reactant was reduced remarkably.Total yield was 43.3%from p-methyl aniline.This technology possessed the character of mild reaction condition,higher yield and well foreground of industrial application by using of benzoic diazonium as reactant.Moreover,some kinds of phenanthrene carboxylic acid were prepared successfully.