CN106831436A - A kind of method of preparation and its removing of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA - Google Patents

A kind of method of preparation and its removing of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA Download PDF

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CN106831436A
CN106831436A CN201710034073.6A CN201710034073A CN106831436A CN 106831436 A CN106831436 A CN 106831436A CN 201710034073 A CN201710034073 A CN 201710034073A CN 106831436 A CN106831436 A CN 106831436A
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base
group
dmna
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hydroxyl
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孙建松
刘慧�
廖进喜
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Jiangxi Normal University
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    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
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    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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Abstract

A kind of method of preparation and its removing of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA, a kind of efficient introducing of the dimethyl benzene acetyl group of sugared hydroxyl protecting group 2,2 of step (1) on carbohydrate hydroxyl；Step (2) is by the efficient removal of the hydroxyl protecting group；

Description

A kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA preparation and its removing Method
Technical field
The present invention relates to chemical field, more particularly to a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA preparation and The method of its removing.
Background technology
Sugar, also known as carbohydrate, four classes are important together with protein, nucleic acid and lipid and referred to as during vital movement Large biological molecule, sugar is molecule important in life entity, and it take part in life entity, especially the fertilization of many cells life entity, All Time and the steric course such as implantation, differentiation, development, immune, infection, canceration, aging, and with the close phase of various diseases Close, however, generally there are the close multiple reaction sites of reactivity in monosaccharide molecule, we often only want to one of work Property site keep activity, other sites must selective protection rise and won't do participation reaction, or protected by special protection group and As potential avtive spot, therefore, in carbohydrate chemistry synthesis, efficiently introduce and selectively removing protection group must as one kind Indispensable important means, for a long time, substantial amounts of researcher has developed a series of distinctive selectivity sugar of tools The guard method of hydroxyl, serves huge effect in the historical development of carbohydrate chemistry, the activity of each hydroxyl in saccharide compound Difference is not very big, therefore how the protection of efficient selective ground and deprotection will necessarily be a weights that carbohydrate chemistry synthesizes field Want problem, although existing substantial amounts of hydroxyl protecting group at present, but still far can not meet the need for modern carbohydrate chemistry synthesizes, because The new hydroxyl protecting group of this development is particularly urgent.
Valeryl (Piv) is widely applied very much as traditional hydroxyl protecting group in synthesis, for example, Using Piv protection groups as 2 hydroxyl protecting groups of sugared ring, not only acted on neighboring group participation when there is glycosylation reaction, and Because its steric hindrance is big so that it is difficult to form ortho esters, and then can be very good to obtain 1,2 trans-glycoside products.But Piv Too stable under the conditions of a lot, the condition for causing it to remove is often relatively more violent, in order that its more convenient removing, 1998, Crimmins etc. has developed the hydroxyl protecting group of similar 2,2- dimethyl -4- pentenoyls, and the protection group is using intramolecular Ring closure reaction is removed, hydroxyl required for exposing [Crimmins.T.M.et al.Tetrahedron Lett.1998,39, 7005], Trost in 1999 etc. also using the similar protections of the Piv of carbochain extension when (+)-Cyclophellitol is synthesized Base, the protection group can equally remove silicon substrate in the presence of HF/Py, and then Intra-molecular condensation occurs and removes [Trost, B.M.et al.Tetrahedron Lett.1999,40,219], but above-mentioned protection group removing be both needed to acid or Under person's alkalescence condition, the exposed hydroxyl of generation γ, then carry out intramolecular cyclization and remove, under this condition for intramolecular It is that may be present some can not have good compatibility to sour or alkali-sensitive blocking group.
2001, Sekine etc. reported a kind of new hydroxyl protecting group-neighbour's azido benzoyl base (AZMB), the protection It is exactly that nitrine can be reduced into amino and then generation point using various reduction means in removing that most obvious one of base is improved Cyclization generation acid amides in son is removed again, and this improvement causes the protection group such as other esters and silicon ethers present in molecule
[Sekine, M.et al.Tetrahedron Lett.2001,42,1069] unaffected when AZMB is removed.
The content of the invention
It is an object of the invention to provide a kind of preparation and its removing of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA Method, the protection group is not only easy to prepare, and can efficiently introduce and remove, and reaction condition is gentle, and orthogonality is strong, the scope of application Extensively.
What the present invention was realized in：
Step 1：A kind of efficient introducing of sugared hydroxyl protecting group 2,2- dimethyl-phenylacetyl group on carbohydrate hydroxyl；Step 2：By the efficient removal of the hydroxyl protecting group；
Wherein, R1It is the one kind in methyl or ethyl, R2It is that a hydroxyl or other exposed hydroxyls of multiple hydroxyls are protected Glycosyl, wherein glycosyl be β-D-Glucose base, alpha-D-glucose base, β-D- galactosyls, α-D- galactosyls, β-D- sweet dews Glycosyl, α-D-MANNOSE base, β-D- xylosyls, alpha-D-xylose base, β-D-2- aminoglucoses glycosyl, α-D-2- Glucosamines Base, α-L- rhamanopyranosyls, β-L- rhamanopyranosyls, α-D-ribose base, β-D-ribose base, α-L- ribosyls, β-L- ribosyls, α-D- Aralino, β-D-R base, α-L-arabinose base, β-L-arabinose base, α-L-fucose base, β-L- rock algaes In glycosyl, β-D-Glucose aldehydic acid base, alpha-D-glucose aldehydic acid base, β-D- galacturonics acidic group, α-D- galacturonic acidic groups One kind, wherein sugar on protection group for acetyl group, benzoyl, benzyl, acetaldehyde fork, acetonylidene, silicon substrate, pi-allyl, to methoxy Phenoxyl, AZMB structural formulas are
In step 1, described introducing method is 2,2- dimethyl-(2 '-nitro) phenylacetic anhydride (DMNAA) 2 and hydroxyl Exposed glycosyl compound 3 in organic solvent with inert gas shielding under, in the presence of drier, urged lewis acidic Under change effect, there is the compound 1 that acylation reaction generates hydroxyl protection；Wherein described lewis acid is TFMS trimethyl Estersil (TMSOTf)；The drier isMolecular sieve or picklingMolecular sieve, the inert gas is high-purity Nitrogen, argon gas or helium.Wherein the mass ratio of substrate and molecular sieve is 1：2-10, compound 2 (DMNAA), compound 3, road The mol ratio of Lewis acid is 1：0.5-1.0：0.5-1.0, reaction temperature is -36 DEG C, and the reaction time is 0.5-4 hours, described to have Machine solvent is the one kind in the alkyl halide of C1-C4.
The step of 2 in, the efficient removal of the hydroxyl protecting group is：Compound 1 in organic solvent, in reducing agent Under effect, remove, obtain the exposed compound 3 of hydroxyl, wherein the reducing agent be Zn, the solvent be dichloromethane, Methyl alcohol, 1,4- dioxane, water one of which or two kinds.
The solution have the advantages that：With easily prepared, efficient introducing, easily operated, efficient removal, environmental protection, Advantage applied widely, and the protection group is when being applied to 2 hydroxyl protections of glycosyl donor, with good three-dimensional selection Property, it is thus advantageous to the development and application of the protection group.
Specific embodiment
The present invention is described in detail below in conjunction with embodiment 1-10 to be had the advantage that, it is intended to help reader more preferable Ground understands essence of the invention, but can not constitute any restriction to implementation of the invention and protection domain.
The room temperature being related in following each embodiments is 20~35 DEG C.
Embodiment 1
- O- benzoyls-the 6-O- of methyl 2,3,4- tri- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- pyrroles The preparation of glucopyranoside glycosides,
Step 1：Protection group 2, the preparation of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA), under ice bath, by 10g neighbour's nitre Base phenylacetic acid is dissolved in 200mL methanol solutions, is slow added into 30mL thionyl chlorides, under ice bath, reacts 30 minutes, and TLC monitorings are anti- Should terminate, be concentrated under reduced pressure crude product, column chromatography obtains o-nitrophenyl acetic acid methyl esters 10g, yield 93%；
Above-mentioned products therefrom 10g is dissolved in 100mL DMFs, under ice bath, 6.15g hydrogenations is slowly added to Sodium, is slowly added dropwise 9.8mL iodomethane, and reaction system is slowly increased into room temperature, reacts 12 hours, and TLC monitoring reactions terminate, acetic acid Ethyl ester diluting reaction system, washing, saturated sodium-chloride is washed, anhydrous sodium sulfate drying, and be concentrated under reduced pressure to obtain crude product, and column chromatography must be produced Thing 11g, yield 96%；
Above-mentioned product 10.5g is dissolved in 100mL, volume ratio for methyl alcohol：Water=1:1 solution, adds the NaOH of 8M Solution 20mL, flow back 48 hours, TLC monitoring reactions terminate, and add the watery hydrochloric acid of 1M, and PH is adjusted into 2~3, add dichloromethane Alkane is extracted 3 times, collects organic phase, and anhydrous sodium sulfate drying is concentrated under reduced pressure, and column chromatography obtains 9.2g, and yield is 94%；
Above-mentioned products therefrom 1g is dissolved in dry 10mL dichloromethane, N, N- dicyclohexylcarbodiimides (DCC) is added 1.1g, room temperature reaction 3 hours, TCL monitoring reactions terminate, and filter, and be concentrated under reduced pressure to obtain crude product, and column chromatography obtains required product 2,2- Dimethyl-(2 '-nitro) phenylacetic anhydride (DMNAA) 917mg, yield is 96%.
Step 2：Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Under nitrogen protection, by-O- benzoyl -6- hydroxyl-alpha-D- glucopyranoside the 50.6mg of methyl 2,3,4- tri-, 0.1mmol, 2,2- dimethyl-(2 '-nitro) phenylacetic anhydride (DMNAA) 60mg, 0.15mmol, the 5A MS of activation are dissolved in drying 2mL dichloromethane, reacted 10 minutes in -36 DEG C, then 0.2mL Trimethylsilyl trifluoromethanesulfonates are dissolved in 5mL dichloromethane In, l mL solution is taken, and stirred 40 minutes in -36 DEG C, TLC tracks to reaction to be terminated, and reaction, dichloro is quenched with triethylamine methyl alcohol Methane diluting reaction system, saturated sodium bicarbonate is washed three times, and saturated sodium-chloride is washed twice, anhydrous sodium sulfate drying, filtering decompression Crude product is concentrated, then column chromatography obtains required product 63mg, 91%；[α]D 25=+48.2 (c 1.00, CHCl3)；1H NMR (400MHz,CDCl3) δ 7.99-7.95 (m, 3H), 7.92 (dd, J=1.2,8.0Hz, 2H), 7.85 (dd, J=1.2,8.4Hz, 2H), 7.62-7.60 (m, 2H), 7.52 (td, J=1.2,8.4Hz, 2H), 7.45-7.28 (m, 8H), 6.11-6.05 (m, 1H), 5.42 (t, J=9.6Hz, 1H), 5.15-5.11 (m, 2H), 4.35 (d, J=9.6Hz, 1H), 4.24-4.18 (m, 2H), 3.31 (s,3H),1.70(s,3H),1.67(s,3H)；13C NMR(100MHz,CDCl3)δ174.9,165.8,165.7,165.2, 148.5,139.1,133.3,133.2,133.0,129.9,129.8,129.6,129.2,129.0,128.9,128.4(2C), 128.2,128.1,127.7,125.8,96.8,72.0,70.4,69.3,67.4,63.3,55.3,46.4,27.2,27.1； HRMS(ESI)calcd for C38H35NO12Na[M+Na]+720.2051found 720.2091；
Step 3：- O- benzoyls-the 6-O- of methyl 2,3,4- tri- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group) - The selectively removing of DMNA protection groups on α-D- glucopyranosides,
By-O- benzoyls-the 6-O- of methyl 2,3,4- tri- (2,2- dimethyl -2- (O-Nitrophenylfluorone) acetyl group)-α-D- Glucopyranoside 69.7mg (0.1mmol) is dissolved in 2mL 1,4- dioxane：Water=1:1 solvent, adds 64mg (1mmol) Zinc powder, anhydrous cupric sulfate 15.8mg, glacial acetic acid 28.5uL, reacts half an hour at room temperature, and TLC monitoring reactions terminate, and filter, dichloro Dilution filtrate, saturated sodium bicarbonate is washed twice, and saturated sodium-chloride is washed, anhydrous sodium sulfate drying, is concentrated under reduced pressure, and column chromatography must be by first - O- benzoyl -6- hydroxyl-alpha-D- glucopyranoside the 49.6mg of base 2,3,4- tri-, yield is 98%.
Embodiment 2
- O- benzyls-the 6-O- of methyl 2,3,4- tri- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- pyrans Portugal The preparation of polyglycoside,
Step 1：Synthetic method is shown in such as the step of embodiment 11；
Step 2：Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12, (yield 87%), [α]D 25=+21.5 (c 1.00, CHCl3)；1H NMR(400MHz,CDCl3) δ 7.90 (d, J=8.0Hz, 1H), 7.58 (d, J=4.0Hz, 2H), 7.39-7.24 (m, 16H), 4.96 (d, J=10.8Hz, 1H), 4.80-4.75 (m, 3H), 4.66 (d, J=12.0Hz, 1H), 4.55 (d, J=3.6Hz, 1H), 4.47-4.42 (m, 2H), 4.14 (dd, J=6.0,12.0Hz, 1H), 3.97 (t, J=9.2Hz, 1H), 3.77-3.72 (m, 1H), 3.44 (dd, J=3.2,9.6Hz, 1H), 3.29 (dd, J=8.8,10.4Hz, 1H), 3.21 (s, 3H), 1.67 (s, 3H),1.66(s,3H)；13C NMR(100MHz,CDCl3)δ175.0,148.6,139.2,138.6,138.1,137.9, 133.2,128.4(2C),128.0(2C),127.9,127.8,127.7(2C),125.6,97.7,81.9,79.9,78.1, 75.8,75.1,73.3,68.6,63.7,54.9,46.6,27.2；HRMS(ESI)calcd for C38H41NO9Na[M+Na]+ 678.2673found678；
Step 3：- O- benzyls-the 6-O- of methyl 2,3,4- tri- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- The selectively removing of DMNA protection groups on glucopyranoside,
Synthetic method is shown in such as the step of embodiment 13；(yield 98%).
Embodiment 3
- O- benzyls-the 4-O- of 2,3,6- tri- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- glucopyranoses The preparation of glycosides,
Step 1：Synthetic method is shown in such as the step of embodiment 11；
Step 2：Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12, (yield 90%), [α]D 25=+61.0 (c 0.84, CHCl3)；1H NMR(400MHz,CDCl3) δ 7.83 (dd, J=1.2,8.4Hz, 1H), 7.55 (td, J=1.2,8.0Hz, 1H), 7.48 (dd, J =1.6,8.0Hz, 1H), 7.40-7.36 (m, 3H), 7.32-7.22 (m, 13H), 5.04 (t, J=9.6Hz, 1H), 4.97 (d, J =11.6Hz, 1H), 4.68-4.62 (m, 3H), 4.56-4.49 (m, 3H), 3.92 (t, J=9.2Hz, 1H), 3.83-3.78 (m, 1H), 3.71 (dd, J=1.6,10.8Hz, 1H), 3.63-3.57 (m, 2H), 3.39 (s, 3H), 1.55 (s, 3H), 1.52 (s, 3H)；13C NMR(100MHz,CDCl3)δ174.3,148.8,138.7,138.6,138.4,137.8,133.0,128.4, 128.2,128.1(2C),127.9(2C),127.8,127.4,127.1,126.9,125.5,97.6,79.8,78.9,74.3, 73.4,73.1,71.2,69.1,69.0,55.4,46.9,27.1,27.0；HRMS(ESI)calcd for C38H41NO9Na[M +Na]+678.2673found 678.2668；
Step 3：The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13；(yield 97%).
Embodiment 4
- O- acetyl group-the 4-O- of 2,3- bis- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group) -6-O- benzyl α-D- pyrroles The preparation of glucopyranoside glycosides,
Step 1：Synthetic method is shown in such as the step of embodiment 11；
Step 2：Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12；(yield 98%), [α]D 25=59.4 (c 1.06, CHCl3)；1H NMR(400MHz,CDCl3) δ 7.94 (dd, J=1.2,8.0Hz, 1H), 7.63 (td, J=1.2,7.6Hz, 1H), 7.54 (dd, J =1.2,8.0Hz, 1H), 7.45-7.41 (m, 1H), 7.37-7.25 (m, 5H), 5.51 (t, J=9.6Hz, 1H), 5.15 (t, J =10.0Hz, 1H), 4.95 (d, J=3.6Hz, 1H), 4.88 (dd, J=3.6,10.0Hz, 1H), 4.68 (d, J=12.0Hz, 1H), 4.51 (d, J=12.0Hz, 1H), 3.91-3.86 (m, 1H), 3.64-3.55 (m, 2H), 3.41 (s, 3H), 2.05 (s, 3H),2.04(s,3H),1.55(s,3H),1.53(s,3H)；13C NMR(100MHz,CDCl3)δ174.1,170.2,170.1, 148.4,138.4,138.1,133.4,128.3,12.8,128.0,127.8,127.5,125.8,96.5,73.4,71.4, 69.7,69.6,68.9,68.6,55.3,46.7,26.9,26.8,20.9,20.7；HRMS(ESI)calcd for C28H34NO11[M+H]+560.2126found 560.2131；
Step 3：The selectively removing of DMNA protection groups,
Synthetic method is as shown in the step 3 of embodiment 1；(yield 93%).
Embodiment 5
- O- benzoyls-the 4-O- of 2,3- bis- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group) -6-O- benzyl-alphas - The preparation of D- glucopyranosides,
Step 1：Synthetic method is shown in such as the step of embodiment 11；
Step 2：Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12, (yield 95%), [α]D 25=152.9 (c 1.00, CHCl3)；1H NMR(400MHz,CDCl3) δ 7.94 (d, J=7.2Hz, 4H), 7.80 (dd, J=1.6,8.4Hz, 1H), 7.57-7.53 (m, 1H), 7.50-7.46 (m, 2H), 7.44-7.28 (m, 11H), 5.97 (t, J=10.0Hz, 1H), 5.45 (t, J=10.0Hz, 1H), 5.20 (d, J=3.6Hz, 1H), 5.15 (dd, J=3.6,10.0Hz, 1H), 4.75 (d, J=12.0Hz, 1H), 4.58 (d, J=12.0Hz, 1H), 4.04-4.00 (m, 1H), 3.79 (dd, J=2.4,11.2Hz, 1H), 3.74 (dd, J=5.2, 10.8Hz,1H),3.42(s,3H),1.46(s,3H),1.39(s,3H)；13C NMR(100MHz,CDCl3)δ174.2,165.8, 165.7,148.5,138.3,138.2,133.3,133.2,133.1,129.9,129.8,129.4,129.1,128.3(2C), 127.9,127.5,125.7,96.7,73.5,72.4,70.6,69.4,69.0,68.6,55.5,46.6,26.8,26.6；HRMS (ESI)calcd for C38H38NO11[M+H]+684.2439found 684.2481；
Step 3：The selectively removing of DMNA protection groups,
Synthetic method as shown in the step 3 of embodiment 1, (yield 95%).
Embodiment 6
2-O- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-O- benzyl-L- sandlwoods of -3,4- two are muttered the system of glucosides It is standby,
Step 1：Synthetic method is shown in such as the step of embodiment 11；
Step 2：Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12, (yield 88%), [α] D25=61.3 (c 0.8, CHCl3)；1H NMR (400MHz, CDCl3) δ 7.98 (d, J=8.0Hz, 1H), 7.61 (d, J=3.6Hz, 2H), 7.45-7.41 (m, 1H), 7.36-7.26 (m, 10H), 5.93-5.84 (m, 1H), 5.39 (t, J=2.4Hz, 1H), 5.30-5.24 (m, 1H), 5.20- 5.17 (m, 1H), 4.84 (d, J=10.8Hz, 1H), 4.82 (d, J=1.2Hz, 1H), 4.71 (d, J=11.2Hz, 1H), 4.52 (d, J=10.8Hz, 1H), 4.51 (d, J=10.8Hz, 1H), 4.16-4.10 (m, 1H), 4.00-3.94 (m, 2H), 3.73- 3.66 (m, 1H), 3.09 (t, J=9.2Hz, 1H), 1.69 (s, 3H), 1.66 (s, 3H), 1.16 (d, J=6.0Hz, 3H)；13C NMR(100MHz,CDCl3)δ174.5,148.4,139.2,138.4,138.2,133.7,133.1,128.3,128.2(2C), 128.0,127.7(2C),127.5,125.8,117.3,96.6,79.9,78.0,75.2,71.3,69.0,68.2,67.5, 46.7,27.1,26.9,18.0；HRMS(ESI)calcd for C38H41NO9[M+H]+678.2673found 678.2669；
Step 3：The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13, (yield 96%).
Embodiment 7
2,3-O- isopropylidenes -4-O- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-L- sandlwood pyranosides Preparation,
Step 1：Synthetic method is shown in such as the step of embodiment 11；
Step 2：Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method as shown in the step 2 of embodiment 1, (yield 91%), [α] 26D=-76.1 (c=1.1in CHCl3) 1H NMR (400MHz, CDCl3) δ 7.96 (d, J=8.0Hz, 1H), 7.61 (d, J=4.0Hz, 2H), 7.44-7.40 (m, 1H), 5.94-5.84 (m, 1H), 5.32-5.27 (m, 1H), 5.23-5.19 (m, 1H), 5.02 (s, 1H), 4.85 (dd, J=7.6, 10.0Hz,1H),4.18-4.13(m,1H),4.12-4.06(m,2H),4.02-3.96(m,1H),3.75-3.65(m,1H), 1.70 (s, 3H), 1.69 (s, 3H), 1.54 (s, 3H), 1.33 (s, 3H), 1.25 (d, J=6.4Hz, 3H)；13C NMR (100MHz,CDCl3)δ174.7,148.7,138.9,133.6,133.2,128.4,127.8,125.7,117.8,109.7, 96.2,76.0,75.9,75.5,68.2,64.2,47.0,27.6,27.2(2C),26.5,17.3；HRMS(ESI)calcd for C22H30NO8[M+H]+436.1966found 436.1970。
Step 3：The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13, (yield 95%).
Embodiment 8
- O- benzyls-the 4-O- of 2,3- bis- (2,2- dimethyl -2- (O-Nitrophenylfluorone) acetyl group) -6-O- tert-butyl diphenyls The preparation of silicyl-α-D- glucopyranosides,
Step 1：Synthetic method is shown in such as the step of embodiment 11；
Step 2：Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12, (yield 75%), [α] D25=+20.7 (c1.00, CHCl3)；1H NMR (400MHz, CDCl3) δ 7.67-7.62 (m, 5H), 7.46-7.21 (m, 19H), 4.88 (d, J=11.6Hz, 1H), 4.86 (t, J=8.8Hz, 1H), 4.67 (d, J=12.0Hz, 1H), 4.61 (d, J=3.6Hz, 1H), 4.56 (d, J=12.0Hz, 1H), 4.50 (d, J=11.6Hz, 1H), 3.86-3.71 (m, 4H), 3.58 (dd, J=3.6,9.6Hz, 1H), 3.39 (s, 3H), 1.41(s,3H),1.39(s,3H),1.01(s,9H)；13C NMR(100MHz,CDCl3)δ174.2,148.8,138.7, 138.2,137.9,135.8,135.7,133.8,133.6,132.8,129.5(2C),128.4(2C),128.2,127.9, 127.8,127.6,127.5,127.1,126.9,125.4,97.5,79.9,79.0,74.4,73.2,71.2,70.7,63.4, 55.2,46.6,26.8,26.6,19.3；HRMS(ESI)calcd for C47H54NO9[M+H]+804.3562found 804.3562。
Step 3：The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13, (yield 83%).
Embodiment 9
1,2；3,4- diisopropylidenes -6-O- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- pyrans half The preparation of lactoside,
Step 1：Synthetic method is shown in such as the step of embodiment 11；
Step 2：Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Synthetic method is shown in such as the step of embodiment 12 (yield 96%), [α]D 25=-19.1 (c 1.02, CHCl3)；1H NMR(400MHz,CDCl3) δ 7.91 (dd, J=0.8,8.0Hz, 1H), 7.60-7.59 (m, 2H), 7.42-7.38 (m, 1H), 5.49 (d, J=5.2Hz, 1H), 4.59 (dd, J=2.4,8.0Hz, 1H), 4.36 (dd, J=3.6,11.6Hz, 1H), 4.29 (dd.J=2.4,4.8Hz, 1H), 4.18-4.11 (m, 2H), 4.00-3.96 (m, 1H), 1.69 (s, 3H), 1.68 (s, 3H), 1.44(s,3H),1.42(s,3H),1.31(s,3H),1.30(s,3H)；13C NMR(100MHz,CDCl3)δ175.1,148.7, 139.3,133.1,128.2,127.6,125.5,109.5,108.7,96.2,71.0,70.7,70.5,66.0,64.0,46.5, 27.4,25.9(2C),25.0,24.4；HRMS(ESI)calcd for C22H30NO9[M+H]+452.1915found 452.1911。
Step 3：The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13, (yield 98%).
Embodiment 10
- O- benzyls-the 6-O- of 2,3- bis- (2,2- dimethyl -2- (o-nitrophenyl) acetyl group)-α-D- glucopyranosides Preparation,
Step 1：Synthetic method is shown in such as the step of embodiment 11；
Step 2：Novel protected base 2, the introducing of 2- dimethyl-(2 '-nitro) phenylacetyl group (DMNA),
Except the amount of DMNAA reduces to original half, synthetic method is shown in such as the step of embodiment 12 (yield 80%), [α]D 25=+12.6 (c 0.96, CHCl3)；1H NMR(400MHz,CDCl3) δ 7.84 (d, J=8.0Hz, 1H), 7.50 (d, J= 4.0Hz, 2H), 7.32-7.17 (m, 11H), 4.88 (d, J=11.6Hz, 1H), 4.68 (d, J=12.0Hz, 1H), 4.67 (d, J =11.2Hz, 1H), 4.57 (d, J=12.4Hz, 1H), 4.48 (d, J=3.2Hz, 1H), 4.24 (dd, J=5.2,12.0Hz, 1H), 4.18 (dd, J=2.4,12.0Hz, 1H), 3.69 (t, J=9.2Hz, 1H), 3.62-3.57 (m, 1H), 3.35 (dd, J= 3.6,9.6Hz, 1H), 3.27 (t, J=9.6Hz, 1H), 3.14 (s, 3H), 1.580 (s, 3H), 1.576 (s, 3H)；13C NMR (100MHz,CDCl3)δ175.8,148.8,139.6,139.0,138.4,133.5,128.9,128.8,128.4(2C), 128.3,128.2(2C),128.0,126.0,98.3,81.5,79.8,75.8,73.4,70.6,69.5,64.4,55.2, 46.9,27.6(2C)；HRMS(ESI)calcd for C31H36NO9[M+H]+566.2385found 544.2401；
Step 3：The selectively removing of DMNA protection groups,
Synthetic method is shown in such as the step of embodiment 13, (yield 91%).
Embodiment described above is only that the preferred embodiment of the present invention is described, not to model of the invention Enclose and be defined, on the premise of design spirit of the present invention is not departed from, those of ordinary skill in the art are to technical side of the invention Various modifications and improvement that case is made, all should fall into the protection domain of claims of the present invention determination.

Claims (6)

1. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA preparation and its removing method, it is characterised in that step (1) efficient introducing of a kind of sugared hydroxyl protecting group 2,2- dimethyl-phenylacetyl group on carbohydrate hydroxyl；Step (2) is by the hydroxyl The efficient removal of protection group；
Wherein, R1It is the one kind in methyl or ethyl, R2It is a hydroxyl or the exposed protected sugar of other hydroxyls of multiple hydroxyls Base, wherein glycosyl are β-D-Glucose base, alpha-D-glucose base, β-D- galactosyls, α-D- galactosyls, β-D-MANNOSE Base, α-D-MANNOSE base, β-D- xylosyls, alpha-D-xylose base, β-D-2- aminoglucoses glycosyl, α-D-2- aminoglucoses glycosyl, α-L- rhamanopyranosyls, β-L- rhamanopyranosyls, α-D-ribose base, β-D-ribose base, α-L- ribosyls, β-L- ribosyls, α-D- Ahs Draw primary glycosyl, β-D-R base, α-L-arabinose base, β-L-arabinose base, α-L-fucose base, β-L-fucose In base, β-D-Glucose aldehydic acid base, alpha-D-glucose aldehydic acid base, β-D- galacturonics acidic group, α-D- galacturonic acidic groups one Kind, wherein sugar on protection group for acetyl group, benzoyl, benzyl, acetaldehyde fork, acetonylidene, silicon substrate, pi-allyl, to methoxyl group Phenoxy group, AZMB structural formulas are
2. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA according to claim 1 preparation and its removing side Method, it is characterised in that in the introducing method described in step (1) be 2,2- dimethyl-benzene acetic acids acid anhydride 2 and the exposed glycosyl of hydroxyl Compound 3 in organic solvent with inert gas shielding under, in the presence of drier, under lewis acidic catalytic action, There is the compound 1 that acylation reaction generates hydroxyl protection.
3. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA according to claim 2 preparation and its removing side Method, it is characterised in that compound 2 is 1 with compound 3 and lewis acidic mol ratio：0.5-1.0：0.5-1.0, reaction temperature It it is -36 DEG C, the reaction time is 0.5-4 hours, the organic solvent is the one kind in the alkyl halide of C1-C4.
4. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA according to claim 2 preparation and its removing side Method, it is characterised in that described lewis acid is Trimethylsilyl trifluoromethanesulfonate；Described drier isMolecular sieve Or picklingThe mass ratio of molecular sieve, substrate and molecular sieve is 1：2-10, inert gas is high-purity nitrogen, argon gas Or helium.
5. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA according to claim 1 preparation and its removing side Method, it is characterised in that in organic solvent, generation removing obtains the exposed chemical combination of hydroxyl to compound 1 in the presence of reducing agent Thing 3.
6. a kind of sugared hydroxyl protecting group dimethyl benzene acetyl group DMNA according to claim 5 preparation and its removing side Method, it is characterised in that described reducing agent is Zn, described solvent be selected from dichloromethane, methyl alcohol, 1,4- dioxane, water its In one or two.
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Citations (3)

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Publication number Priority date Publication date Assignee Title
EP0349676A1 (en) * 1988-06-21 1990-01-10 Mercian Corporation Tylosin derivatives and process for producing the same
CN101880305A (en) * 2010-06-23 2010-11-10 大连大学 Preparation method of ginsenoside metabolin M1 fatty acid ester compound
CN102627675A (en) * 2012-03-29 2012-08-08 湖北益泰药业有限公司 Method for preparing cane sugar-6-ester

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0349676A1 (en) * 1988-06-21 1990-01-10 Mercian Corporation Tylosin derivatives and process for producing the same
CN101880305A (en) * 2010-06-23 2010-11-10 大连大学 Preparation method of ginsenoside metabolin M1 fatty acid ester compound
CN102627675A (en) * 2012-03-29 2012-08-08 湖北益泰药业有限公司 Method for preparing cane sugar-6-ester

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Title
KATALIN DARAGICS等: "(2-Nitrophenyl)acetyl: A New, Selectively Removable Hydroxyl Protecting Group", 《ORG. LETT.,》 *
KATALIN DARAGICS等: "(2-Nitrophenyl)acetyl: A New, Selectively Removable Hydroxyl Protecting Group", 《ORG. LETT.》 *
PANAYIOTIS A. PROCOPIOU等: "An extremely fast and efficient acylation reaction of alcohols with acid anhydrides in the presence of trimethylsilyl trifluoromethanesulfonate as catalyst", 《CHEMICAL COMMUNICATIONS (CAMBRIDGE)》 *

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Application publication date: 20170613