Syn the sis and Re ac tions of Highly Pro tected Mannosamines
Jia-Cheng Shieua ( ), Yeng-Jeng Shawa ( ) and Tien-Yau Luha , b* ( )aDe part ment of Chem is try, Na tional Tai wan Uni ver sity, Tai pei, Tai wan 106, R.O.C. bIn sti tute of Chem is try, Ac a de mia Sinica, Nankang, Tai pei, Tai wan 115, R.O.C.
Highly pro tected mannosamine de riv a tives are syn the sized from pro tected glu cose de riv a tives hav ing a free hydroxy group at C2 po si tion. In diummediated allylation of pro tected mannosamine de riv a tives is in ves -ti gated.
Mannosamine 1 is an im por tant aminosugar and is pres -ent in a num ber of nat u rally oc cur ring oli go sac cha rides.1 The com pound can also serve as an im por tant pre cur sor for a num ber of higher homo logues of sugar de riv a tives hav ing dif fer ent kinds of bi o log i cal ac tiv i ties.2 Most pub lished syn -the ses of 1 use arabinose3 or glucal4 as start ing ma te ri als. Sep a ra tion of stereoisomers of in ter me di ates is gen er ally re -quired in these pro ce dures. Equilibraton of 2-glucosamine with 1 un der ba sic con di tions has been re ported, but in low over all con ver sion.5 An ideal ap proach for the syn the sis of mannosamine de riv a tive 3 is to start with a glu cose de riv a tive
2 hav ing a free hydroxy group at C2. In ver sion of con fig u ra -tion by dis place ment of this hydroxy group with an amino group would lead to a con ve nient syn the sis of mannosamine de riv a tives 3 (eq 1).
We re cently re ported a con ve nient pro ce dure for the syn the sis of the highly pro tected glu cose de riv a tive 5 hav ing the de sired free hydroxy group at C2 from the cor re spond ing bisacetonide 4 (eq 2).6 Ac cord ingly, this will be an ideal start -ing point for the syn the sis of highly pro tected mannosamine de riv a tives 3. In this pa per, we ad dress the de tails for the syn the sis and re ac tions of highly pro tected mannosamine de riv a -tives.
RE SULTS AND DIS CUS SION
In the be gin ning of this re search, methyl glucoside 5 was treated with triflic an hy dride to give the cor re spond ing triflate 6 in ex cel lent yield. With out fur ther pu ri fi ca tion, 6 was al lowed to re act with so dium azide to af ford azide 7. Cat -a lytic hydrogenolysis of 7 yielded -amine 8 which w-as fur ther trans formed into the cor re spond ing am ide 9 upon treat ment with ace tic an hy dride.
This prom is ing pre lim i nary in ves ti ga tion prompted us to tackle sev eral re lated sys tems, in par tic u lar, those hav ing a la bile anomeric pro tec tive group. Allyl glucosides 10 was sub jected to the re ac tion with the MeMgI in refluxing ben -zene for 1.5 h to give the cor re spond ing ring open ing prod uct
11 hav ing a free hydroxy group at the C2 po si tion. Sim i lar trans for ma tion as de scribed above yielded the mannosamide de riv a tive 15. It is note wor thy that triphenylphosphine was re quired for the re duc tion of 13.7 At tempts to use other re duc -ing agents re sulted in low iso la tion yield of the amine 13.
Sev eral pro ce dures in the lit er a ture are known to re -Ded i cated to Pro fes sor Sheng-lieh Liu on the oc ca sion of his nine ti eth birth day.
O HO HO H2N OH 1 O OP4 P1O P2O HO P3O O O P4 P1O P2O P3O (1) 3 2 H2N HO O OMe O O O O O OMe O HO O O (2 ) 5 4 MeMg I O O Me O TfO O O O OMe O O O X 6 7 X = N3 8 X = NH2 9 X = NHA c
move the allyl pro tec tive group at the anomeric po si tion. How ever, treat ment of 15 with Pd(PPh3)4 in ace tic acid at 80 C did not yield 16. The acetonide pro tec tive group was also re moved un der these con di tions. In a sim i lar man ner, re ac -tion of 15 with PdCl2 in MeOH at room tem per a ture also pro -duced a mix ture of prod ucts while the acetonide moi ety was gone. Pre sum ably, the pro duc tion of the HCl from this trans -for ma tion would fa cil i tate fur ther deprotection pro cess. Gigg’s pro ce dure was then adopted to isomerize the allyl pro -tec tive group to the cor re spond ing 1-propenyl moi ety.8 It is in ter est ing to note that the re ac tion was stereoselective and only cis-isomer 17 was ob tained. Di rect treat ment of crude 17 with HgO/HgCl2 af forded 16 in 80% over all yield.
In cor po ra tion of an allyl substituent at the anomeric cen ter fur nishes a use ful en try for the ex ten sion of a carbon unit to a sugar mol e cule. Many pro ce dures are known to ac com plish this goal. Re ac tions of car bon nucleophiles with a sugar de riv a tive are well doc u mented. More re cently the use of in dium pro vides a pow er ful ar se nal for this pur -pose. In par tic u lar, the re ac tion can be car ried out in aque ous me dium and ex hib its high stereoselectivity.9 Ac cord ingly, the in dium-mediated allylation of 16 in acetonitrile-water (1:1) or THF-water (1:1) yielded an in sep a ra ble mix ture of 18
and 19 (eq 3). It is note wor thy that wa ter is es sen tial for this re ac tion. In the ab sence of wa ter, no de sired prod uct was ob -tained at all. Acetylation of 18 and 19 af forded the re spec tive ac e tates 20 and 21, the ma jor iso mer 20 be ing ob tained as a crys tal line solid. The stereochemistry as sign ment was based on the NMR data. The cou pling con stants JH4,H5 and JH5,H6 in
20 were 10.2 and 4.8 Hz, re spec tively. In a re lated com pound 22, the acetoxy group at C4 and the acetamido group at C5 are syn. The cou pling con stants JH 4,H5 and JH5 ,H6 in 22 were 4.0
and 8.5 Hz, re spec tively.10 Con se quently, the ab so lute con -fig u ra tion at C4 of the ma jor prod uct 20 should be R and that of the mi nor prod uct 21 should be S.
In sum mary, we have dem on strated a con ve nient pro ce dure for the syn the sis of highly pro tected mannosamine de -riv a tives which can be ex tended to the syn the sis of a va ri ety of higher homo logues of sugar de riv a tives. Fur ther ex ten sion of this re search is in prog ress in our lab o ra tory.
EX PER I MEN TAL SEC TION
Methyl 2-O-trifluoromethanesulfonyl-4,6-O-isopropylidene- -D-glucopyranoside (6)
To a so lu tion of 5 (0.29 g, 1.0 mmol) in dried CH2Cl2 (4.0 mL) at -75 C was added pyridine (0.24 g, 3.0 mmol) and Tf2O (0.85 g, 3.0 mmol). The mix ture was stirred from -75 C to 0 C for 2.5 h, quenched with wa ter (10 mL), and ex tracted with ether (10 mL 2). The com bined or ganic layer was dried (MgSO4), fil tered and the sol vent of the fil trate was evap o -rated in vacuo to give the crude 6 (0.35 g, 82%), which was un sta ble and used for the next re ac tion im me di ately. 1H NMR (300 MHz, CDCl3) 1.19 (s, 9H), 1.37 (s, 3H), 1.45 (s, 3H), 3.40 (s, 3H), 3.42-3.47 (m, 1H), 3.60-3.72 (m, 2H), 3.80-3.88 (m, 1H), 3.98 (t, J = 9.2 Hz, 1H), 4.51 (dd, J = 9.2, 3.6 Hz, O O O X O O O O O O X 11 X = O H 12 X = O Tf 13 X = N3 14 X = NH2 15 X = NHAc O O O O O O O 10 O O O O NHAc OH 16 O O O O NHA c 17 O O O O O NHAc OH 16 Br In OH O O O NHAc OH OH O O O NHAc OH 18 19 THF-H2O(1:1) MeCN-H2O (1:1) 56% 79% 44%21% O Ac O O O NHAc OAc OAc O O O NHAc O Ac O Ac O O AcO NHAc OAc CO2B u t H5 H4 H4 H5 H5 H4 H6 H6 H6 20 2 1 22
1H), 4.91 (d, J = 3.6 Hz, 1H); 13C NMR (75 MHz, CDCl3) 19.0, 28.9, 29.3, 55.5, 62.2, 63.9, 64.2, 68.9, 73.8, 75.8, 84.4, 97.8, 99.5; 19F NMR (300 MHz, CDCl3) -75.9.
Methyl butyl- -D-mannopyranoside (7)
A DMF so lu tion (5 mL) of 6 (0.35 g, 0.83 mmol) was treated with NaN3 (0.26 g, 4.2 mmol) and the mix ture was stirred at 80 C for 16 h. Wa ter (10 mL) was added and the mix ture was ex tracted with ether (10 mL). The or ganic phase was dried (MgSO4), fil tered and the sol vent of the fil trate was re moved in vacuo to give the res i due which was chromato -graphed on sil ica gel (Hex ane/EtOAc = 19/1) to af ford 7 as a white solid (0.20 g, 77%): mp 54-56 C; [ ]D24 = +72.4 (c 0.8, CHCl3); 1H NMR (300 MHz, CDCl3) 1.20 (s, 9H), 1.35 (s, 3H), 1.48 (s, 3H), 3.31 (s, 3H), 3.56 (br q, J = 8.5 Hz, 1H), 3.71-3.84 (m, 4H), 3.82 (dd, J = 9.5, 9.4 Hz, 1H), 3.95 (dd, J = 9.4, 3.8 Hz, 1H), 4.54 (s, 1H); 13C NMR (75 MHz, CDCl3) 19.3, 28.4, 29.2, 54.8, 62.3, 65.1, 69.3, 70.1, 75.0, 99.7, 100.3; IR (neat) 2928, 2865, 2107, 1759, 1463, 1374, 1308, 1264, 1197, 1134, 1026, 970, 893, 864, 801 cm-1; Anal. calcd for C14H25O5N3: C, 53.32; H, 7.99. Found: C, 52.72; H, 7.91.
Methyl butyl- -D-mannopyranoside (8)
A mix ture of 7 (0.42 g, 1.3 mmol) and Pd/C (0.76 g) in eth a nol (50.0 mL) was stirred un der an at mo sphere of H2 for 8 h. The mix ture was fil tered through Celite and the sol vent of the fil trate was evap o rated in vacuo to af ford the crude 8 (0.22 g, 58%): 1H NMR (300 MHz, CDCl3) 1.11 (s, 9H), 1.28 (s, 3H), 1.42 (s, 3H), 3.16 (m, enbodied sin glet for CH3 group at 3.24, 4H), 3.52-3.60 (m, 1H), 3.60-3.88 (m, 4H), 4.80 (s, 1H); 13C NMR (75 MHz, CDCl3) 19.4, 28.4, 29.0, 54.6, 55.9, 62.2, 64.8, 67.0, 69.4, 74.8, 99.7, 100.5; IR (neat) 3375, 3306, 2975, 2938, 2912, 2878, 2835, 1594, 1471, 1381, 1367, 1329, 1199, 1172, 1089, 971, 946, 885 cm-1. Methyl tert- butyl- -D-mannopyranoside (9)
A mix ture of 8 (0.22 g, 0.75 mmol), ace tic an hy dride (1.42 g, 13.9 mmol) and pyridine (0.93 g, 11.6 mmol) in CH2Cl2 (20 mL) was stirred at 40 C for 13 h. The mix ture was quenched with wa ter (10 mL) and ex tracted with ether (20 mL). The or ganic phase was dried (MgSO4), fil tered and the sol vent of the fil trate was re moved in vacuo to give the res i due which was chromatographed on sil ica gel (Hex -ane/EtOAc = 19/1) to af ford 9 as a white solid (0.2 g, 77%): mp 88-90 C; [ ]D2 7 = +72.4 (c 2.5, CHCl3); 1H NMR (400 MHz, CDCl3) 1.15 (s, 9H), 1.36 (s, 3H), 1.47 (s, 3H), 1.98 (s, 3H), 3.31 (s, 3H), 3.52 (t, J = 10.0 Hz, 1H), 3.64 (dt, J = 10.0, 4.8 Hz, 1H), 3.73 (t, J = 10.0 Hz, 1H), 3.80 (dd, J = 10.0, 4.8 Hz, 1H), 3.91 (dd, J = 10.0, 5.2 Hz, 1H), 4.20 (ddd, J = 6.8, 5.2, 0.8 Hz, 1H), 4.71 (d, J = 0.8 Hz, 1H), 5.78 (d, J = 6.8 Hz, 1H); 1 3C NMR (50 MHz, CDCl3) 19.2, 23.3, 28.2, 29.1, 54.3, 62.3, 64.2, 66.3, 70.5, 74.8, 99.6, 100.7, 170.6; IR (KBr) 3262, 3201, 3080, 2981, 2951, 2908, 2876, 2834, 2250, 1654, 1632, 1562, 1472, 1443, 1380, 1269, 1202, 1129, 1074, 1040, 985, 957, 918, 887, 863, 731 cm-1; HRMS calcd for C16H29O6N 331.1995. Found 331.1998; Anal. calcd for C16H29NO6: C, 57.97; H, 8.82. Found: C, 57.67; H, 8.54.
Allyl O2,O3;O4,O6-Bis-isopropylidene- glucopyranoside (10)
A mix ture of allyl -D-glucopyranoside (3.82 g, 17.3 mmol), TsOH (0.04 g, 0.21 mmol) and 2-methoxypropene (10 mL, 69 mmol), in dry DMF (50 mL) was stirred for 2 h at 20 C. The mix ture was poured into wa ter (100 mL) and ex -tracted with ether (50 mL 2). The or ganic phase was dried (MgSO4) and the sol vent was re moved in vacuo to af ford 10 as an oil (4.56 g, 88%): [ ]D2 7 +86.6 (c 0.05, CHCl3); 1H NMR (CDCl3, 200 MHz) 1.38 (s, 3H), 1.39 (s, 3H), 1.42 (s, 3H), 1.49 (s, 3H), 3.45-3.59 (m, 2H), 3.71-3.88 (m, 3H), 3.97-4.23 (m, 3H), 5.11-5.18 (m, 2H, em bod ied a dou blet, J = 3.0 Hz), 5.27 (dq, J = 17.2, 1.4 Hz, 1H), 5.89 (ddt, J = 17.2, 10.9, 5.3 Hz, 1H); 13C NMR (CDCl3, 50 MHz) 19.0, 26.3, 26.7, 28.9, 62.2, 65.0, 68.7, 73.7, 73.9, 76.7, 96.9, 99.5, 111.3, 117.4, 133.4; Anal calcd for C1 5H24O6: C, 59.98; H, 8.05. Found C, 59.94; H, 8.12.
Allyl O3-tert-Butyl-O4,O6-isopropylidene- glucopyranoside (11)
A ben zene so lu tion (20 mL) of 10 (0.92 g, 3.06 mmol) was al lowed to re act with MeMgI (2.4 mL, 2 M ether, 6.1 mmol) at 50-60 C for 1.5 h. The mix ture was quenched with NH4Cl so lu tion. The or ganic layer was sep a rated, and the aque ous so lu tion was ex tracted with ether. The com bined or -ganic lay ers were washed suc ces sively with wa ter and brine and dried (MgSO4) to af ford 11 (0.83 g, 86%) as a col or less oil: [ ]D2 7 +110.8 (c 0.05, CHCl3); 1H NMR (CDCl3, 200 MHz) 1.21 (s, 9H), 1.37 (s, 3H), 1.44 (s, 3H), 2.06 (d, J = 7.9 Hz, 1H), 3.30-3.35 (m, 2H), 3.55-3.88 (m, 4H), 4.04 (dd, J = 12.8, 6.4 Hz, 1H), 4.22 (dd, J = 12.8, 5.4 Hz, 1H), 4.92 (d, J = 3.8 Hz, 1H), 5.21 (dd, J = 10.2, 1.5 Hz, 1H), 5.29 (dd, J = 17.3, 1.5 Hz, 1H), 5.92 (ddt, J = 17.3, 10.2, 5.7 Hz, 1H); 13C NMR (CDCl3, 50 MHz) 19.0, 29.0, 29.3, 62.5, 64.3, 68.5, 72.2, 72.4, 73.3, 74.5, 98.3, 99.1, 118.0, 133.6; HRMS calcd for C16H2 8O6: 316.1886, found: 316.1889; Anal calcd: C, 60.74; H, 8.92. Found C, 60.74; H, 9.06.
Allyl 2-Azido-2-deoxy-O3-tert-butyl-O4,O6 isopropylidene- -D-mannopyranoside (13)
To a CH2Cl2 so lu tion (60 mL) of 11 (3.0 g, 9.5 mmol) and pyridine (1.5 mL, 19.0 mmol) at -10 C was added Tf2O (1.2 mL, 11.4 mmol) over a pe riod of 30 min, and the mix ture was stirred for 2 h at 0 C. Ice-cooled wa ter (20 mL) was then in tro duced. The aque ous layer was ex tracted with ether (50 mL), and the com bined or ganic lay ers were dried (MgSO4). The sol vent was re moved in vacuo to yield the crude 12 (3.6 g, 8.8 mmol, 93%) which was dis solved in DMF (60 mL). NaN3 (2.86 g, 44.0 mmol) was added, and the mix ture was stirred at 80 C for 18 h. Then wa ter was in tro duced, and the mix ture was ex tracted with ether (60 mL). The or ganic layer was suc ces sively washed with wa ter and brine and dried (MgSO4). The sol vent was re moved in vacuo to give the res i -due which was chromatographed on sil ica gel (Hex ane/ EtOAc = 4/1) to af ford the 13 (2.17 g, 72%) as a col or less oil: [ ]D2 9 +72.4 (c 0.05, CHCl3); 1H NMR (CDCl3, 200 MHz) 1.22 (s, 9H), 1.36 (s, 3H), 1.49 (s, 3H), 3.50-4.05 (m, 7H), 4.13 (ddt, J = 12.9, 5.3, 1.2 Hz, 1H), 4.50 (d, J = 1.2 Hz, 1H), 5.20 (dq, J = 11.5, 1.5 Hz, 1H), 5.27 (dq, J = 17.1, 1.5 Hz, 1H), 5.88 (dddd, J = 17.1, 11.5, 6.2, 5.2 Hz, 1H); 13C NMR (CDCl3, 50 MHz) 19.3, 28.4, 29.2, 62.2, 65.3, 65.4, 68.1, 69.3, 70.2, 75.0, 98.4, 99.7, 117.9, 133.4; IR (neat) 2110 cm-1; Anal calcd for C16H2 7N3O5: C, 56.29; H, 7.97; N, 12.31. Found C, 56.34; H, 8.32; N, 12.14.
Allyl 2-Amino-2-deoxy-O3-tert-butyl-O4,O6 isopropylidene- -D-mannopyranoside (14)
Ph3P (2.52 g, 9.60 mmol) was added to a so lu tion of 13 and the mix ture was stirred at am bi ent tem per a ture for an ad -di tional 12 h. Hex ane (50 mL) was in tro duced, and the slurry was fil tered. The fil trate was dried (MgSO4), and the sol vent was re moved in vacuo to give the res i due which was chro -matographed on sil ica gel (Hex ane/EtOAc = 2/1) to af ford 14 (2.34 g, 78%) as a col or less oil: [ ]D29 +57.4 (c 0.05, CHCl3); 1 H NMR (CDCl3, 200 MHz) 1.17 (s, 9H), 1.35 (s, 3H), 1.46 (s, 3H), 3.11 (br, 1H), 3.60-3.85 (m, 7H), 3.39 (ddt, J = 13.0, 6.1, 1.2 Hz, 1H), 4.13 (ddt, J = 13.0, 5.2, 1.2 Hz, 1H), 4.73 (br s, 1H), 5.14-5.31(m, 2H), 5.89 (ddt, J = 17.3, 10.4, 5.5 Hz, 1H); 13C NMR (CDCl3, 50 MHz) 19.2, 28.6, 29.2, 56.2, 62.5, 65.1, 67.9, 68.6, 69.8, 74.3, 99.5, 100.9, 117.3, 133.9; HRMS calcd for C1 6H29NO5: 315.2046, found: 315.2034; Anal calcd: C, 60.93; H, 9.27; N, 4.44. Found C, 60.92; H, 8.99; N, 3.95.
Allyl tert- butyl- -D-mannopyranoside (15)
To a so lu tion of 14 (3.01 g, 9.55 mmol) in CH2Cl2 (30
mL) was added pyridine (0.9 mL, 11.5 mmol), and the mix ture was cooled to 0 C. Af ter a brief stir ring, ace tic an hy -dride (1.3 mL, 14.3 mmol) was added, and the mix ture was stirred over night at room tem per a ture. The re ac tion was quenched with wa ter (10 mL) and di luted with CH2Cl2 (100 mL). The or ganic layer was washed with acqueous CuSO4 so -lu tion (0.2 M, 50 mL), wa ter (100 mL), and brine (50 mL) and the or ganic layer was dried (MgSO4). Sol vent was re moved
in vacuo to yield 15 (3.23 g, 95%) as a white solid: mp
113-114 C (hex ane); [ D2 6 +38.2 (c 1.00, CHCl3); 1H NMR (CDCl3, 300 MHz) 1.16 (s, 9H), 1.36 (s, 3H), 1.48 (s, 3H), 2.03 (s, 3H), 3.50 (t, J = 8.7 Hz, 1H), 3.60-3.88 (m, 3H), 3.95 (dd, J = 8.7, 6.3 Hz, 1H), 3.88-4.05 (m, 1H), 4.05-4.18 (m, 1H), 4.23 (t, J = 6.3 Hz, 1H), 4.87 (s, 1H), 5.19 (dd, J = 10.3, 1.4 Hz, 1H), 5.28 (dd, J = 17.3, 1.4 Hz, 1H), 5.75 (d, J = 6.3 Hz, 1H), 5.89 (ddt, J = 17.3, 10.3, 5.5 Hz, 1H); 1 3C NMR (CDCl3, 70 MHz) 19.3, 23.5, 28.3, 29.2, 54.6, 62.4, 64.5, 66.4, 68.4, 70.7, 75.0, 99.0, 99.8, 117.5, 133.7, 170.7; HRMS calcd for C18H31NO6: 357.2151, found: 357.2135.
butyl- -D-mannopyranose (16)
To a so lu tion of 15 (0.50 g, 1.59 mmol) in dry DMSO (25 mL) was added tBuOK (0.54 g, 4.77 mmol) and the mix -ture was stirred at 70 C for 30 min. Af ter cool ing to rt, the mix ture was poured into ice-water (50 mL) and ex tracted with EtOAc (100 mL). The or ganic layer was washed with wa ter (2 100 mL), dried (MgSO4) and con cen trated in
vacuo to give crude 17 which was treated with HgCl2 (0.86 g, 3.18 mmol) and HgO (0.69 mg, 3.18 mmol) in ac e tone-water (4:1, 25 mL) for 30 min. The mix ture was fil tered through char coal and the fil trate was di luted with EtOAc (200 mL) and washed suc ces sively with H2O (50 mL) and brine (2 50 mL), and dried (MgSO4). Sol vent was re moved in vacuo to yield the res i due which was chromatographed on sil ica gel (EtOAc/Hex ane = 1/1) to af ford 16 (MgSO4) as a mix ture of anomeric iso mers (0.35 g, 79%, ma jor:mi nor = 4:1): [ ]D2 6 -25.0 (c 1.00, CHCl3); 1H NMR (CDCl3, 300 MHz) 1.16 (s, 7.2H), 1.16 (s, 1.8H), 1.35 (s, 3H), 1.45 (s, 0.6H), 1.46 (s, 2.4H), 2.02 (s, 2.4H), 2.12 (s, 0.6H), 3.25 (dt, J = 9.9, 5.2 Hz, 0.2H), 3.42-3.57 (m, 1H, em bod ied a trip let, J = 9.8 Hz), 3.62-4.07 (m, 3.8H), 4.19 (t, J = 6.1 Hz, 1H), 4.47 (d, J = 4.1 Hz, 0.8H), 4.82 (d, J = 7.3 Hz, 0.2H), 5.21 (d, J = 4.1 Hz, 0.8H), 5.92 (d, J = 6.1 Hz, 0.8H), 6.04 (d, J = 4.4 Hz, 0.2H), 6.79 (d, J = 7.3 Hz, 0.2H); 13C NMR (CDCl3, 70 MHz) 19.2, 19.3, 23.2, 23.4, 28.3, 28.4, 29.0, 29.1, 55.4, 57.3, 62.2, 62.4, 64.4, 66.1, 68.8, 69.2, 70.4, 70.7, 75.1, 75.5, 93.9, 96.1, 99.7, 99.8, 171.3, 174.2; Anal calcd for C1 5H27NO6: C, 56.77; H, 8.57; N, 4.41. Found C, 56.35; H, 8.62; N, 4.38.
Allylation of 16
To a so lu tion of 16 (0.10 g, 0.32 mmol) and allyl bro -mide (60 L, 0.64 mmol) in 10 mL of aque ous acetonitrile (v/v 1:1) was added in dium power (0.06 g, 0.48 mmol) in one por tion. The mix ture was stirred for 1 h at 0 C and an ad di -tional 6 h at am bi ent tem per a ture. Af ter fil tra tion, the sol vent was re moved in vacuo and the res i due was triturated with EtOAc. The or ganic so lu tion was washed with brine, dried (MgSO4), fil tered, and con cen trated. The res i due was pu ri -fied by col umn chro ma tog ra phy on SiO2 (EtOAc/Hex ane = 3/1) to af ford a diasteroemeric mix ture of 18 and 19 (3.8:1, 0.06 g, 49%), as col or less oil: [ ]D25 = +16.2 (c 2.00, CHCl3); 1
H NMR (CDCl3, 300 MHz) (se lected sig nals) 1.20 (s, t-Bu, mi nor prod uct), 1.21 (s, t-Bu, ma jor prod uct), 1.35, 1.43 (s, Me, mi nor prod uct), 1.41, 1.47 (s, Me, ma jor prod uct), 1.97 (s, CH3Nacetyl, ma jor prod uct), 2.02 (s, CH3Nacetyl, mi -nor prod uct), 5.0-5.2 (m, 2H), 5.70-5.95 (m, 1H,), 6.38 (d, J = 7.9 Hz, NH-acetamide, mi nor prod uct), 6.68 (d, J = 7.9 Hz, NH-acetamide, ma jor prod uct); 13C NMR (CDCl3, 70 MHz) 19.1, 19.5, 23.2, 23.4, 27.9, 28.5, 28.6, 28.8, 38.5, 38.8, 53.6, 57.7, 62.2, 64.9, 65.0, 66.8, 69.8, 71.6, 74.1, 74.7, 74.8, 75.1, 75.7, 98.6, 98.9, 117.5, 117.8, 134.3, 135.0, 170.8, 171.0; IR (neat, cm-1) 526, 684, 912, 995, 1069, 1165, 1195, 1231, 1373, 1530, 1659, 2882, 2943, 2981, 3082, 3407; HRMS calcd for C18H33NO6: 359.2308, found: 359.2326.
Ac e tate 20
To a CH2Cl2 (2 mL) so lu tion of 18 and 19 (0.15 g, 0.42 mmol) and pyridine (90 L, 0.1 mmol) was added Ac2O (100 L, 0.1 mmol), and the mix ture was stirred at room tem per a -ture over night. The so lu tion was di luted with CH2Cl2 (10 mL), then quenched with wa ter (10 mL). The or ganic layer was washed with brine, dried (MgSO4), fil tered, and con cen trated. The crude prod uct was pu ri fied by col umn chro ma tog -ra phy on SiO2 (EtOAc/Hex ane = 1/1) to af ford 20 (0.12 g, 64.3%) as a white solid: mp 97-98 C; [ ]D2 5 -21.5 (c 0.50, CHCl3); 1H NMR (CDCl3, 300 MHz) 1.13 (s, 9H), 1.41 (s, 3H), 1.52 (s, 3H), 1.94 (s, 3H), 1.99 (s, 3H), 2.03 (s, 3H), 2.19-2.33 (m, 1H), 2.40-2.53 (m, 1H), 3.58 (dd, J = 11.9, 6.4 Hz, 1H), 3.80 (dd, J = 4.8, 2.0 Hz, 1H), 4.00 (dd, J = 8.8, 2.0 Hz, 1H), 4.09 (dd, J = 11.9, 5.0 Hz, 1H), 4.49 (ddd, J = 10.2, 8.8, 4.8 Hz, 1H), 4.74-4.89 (m, 2H), 5.00 (d, J = 7.9 Hz, 1H), 5.03 (d, J = 15.2 Hz, 1H), 5.62-5.80 (m, 1H), 6.72 (d, J = 8.9 Hz, 1H); 13C NMR (CDCl3, 70 MHz) 20.9, 20.9, 23.6, 27.3, 28.4, 37.2, 54.6, 61.7, 65.3, 66.8, 72.2, 73.2, 74.6, 99.7, 117.9, 133.6, 169.9, 170.2, 170.7; HRMS calcd for C22H3 7NO8: 443.2519, found: 443.2519. Anal calcd: C, 59.58; H, 8.41; N, 3.16. Found C, 59.51; H, 8.34; N, 3.79.
AC KNOWL EDG MENT
This work was sup ported by the Na tional Sci ence Coun cil and the Min is try of Ed u ca tion of the Re pub lic of China.
Re ceived June 28, 2001.
Key Words
Mannosamines; In dium; Allylation.
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