RSC Advances
Paper
residue was puried by silica gel column chromatography 1H, H-5), 2.67 (m, 1H, OH), 2.45 (m, 1H, OH), 1.08 (s, 9H, tBu),
t
(15 : 1 / 2 : 1 n-hexane/EtOAc) to give 18 (711 mg, 93%, a/b ¼ 1.06 (s, 9H, Bu); 13C NMR (125 MHz, CDCl3): d 136.7, 133.4,
1/1.5) as white foamy material. 18a: 1H NMR (500 MHz, CDCl3): 127.2, 124.3, 118.2, 113.5, 111.4, 110.3, 100.7, 77.2, 73.2, 71.5,
d 8.56 (s, 1H, NH), 8.03–7.35 (m, 10H, Ph), 6.79 (d, 1H, J1,2
¼
70.1, 68.2, 66.8, 27.6, 27.2, 23.4, 20.7. HRMS (ESI-TOF): m/z
38H41BrClNO9Si: 570.0685 [M
Na]+; found:
3.5 Hz, H-1), 6.04 (dd, 1H, J2,3 ¼ 10.5 Hz, H-2), 5.69 (dd, 1H, J3,4 calcd for
C
+
¼ 3.0 Hz, H-3), 5.01 (d, 1H, H-4), 4.34 (dd, 1H, J5,6a ¼ 2.0 Hz, Jgem 570.0688.
¼ 12.5 Hz, H-6a), 4.30 (dd, 1H, J5,6b ¼ 1.5 Hz, H-6b), 4.17 (s, 1H,
5-Bromo-4-chloroindoxyl a-D-galactopyranoside (9). To
t
t
H-5), 1.15 (s, 9H, Bu), 0.98 (s, 9H, Bu); 13C NMR (125 MHz, a solution of 20 (225 mg, 0.395 mmol) in THF (3.9 mL) were
CDCl3): d 166.2, 165.7, 160.8, 133.4, 133.3, 129.9, 129.7, 129.6, added acetic acid (54 mL, 0.948 mmol) and tetrabutylammo-
129.0, 128.4, 124.8, 94.6, 91.0, 70.9, 70.7, 69.8, 67.3, 66.6, 27.5, nium uoride (1.0 M solution in THF, 948 mL, 0.948 mmol) at
27.2, 23.3, 20.8. HRMS (ESI-TOF): m/z calcd for C30H36Cl3NO7Si: 0 ꢀC. Aer stirring for 0.5 h at rt, the completion of the reaction
694.1168 [M + Na]+; found: 694.1172.
was conrmed by TLC (5 : 1 CHCl3/MeOH). Solvents were
N-Acetyl-5-bromo-4-chloroindoxyl 2,3-di-O-benzoyl-4,6-O-di- removed by co-evaporation with toluene. The resulting residue
tert-butylsilylene-D-galactopyranoside (19). A solution of 18 was puried by silica gel column chromatography on Iatrobeads
(200 mg, 0.298 mmol) in CH2Cl2 (1.0 mL) was transferred into 6RS-8060 (10 : 1/ 5 : 1 CHCl3/MeOH) to give 9 (150 mg, 93%)
1
ꢀ
a two-neck round bottom ask, in which pre-activated 4 A as light sky blue powder. [a]D +117.2 (c 1.0 in CHCl3); H NMR
3
molecular sieves (222 mg) were placed, using a cannula at 0 ꢀC. (500 MHz, CD3OD): d 7.28 (d, 1H, Jortho ¼ 9.0 Hz, Ar), 7.25 (s,
To the suspension was transferred a solution of 7 (258 mg, 0.894 1H, C]CH), 7.14 (d, 1H, Ar), 5.38 (d, 1H, J1,2 ¼ 3.5 Hz, H-1), 4.07
mmol) in CH2Cl2 (3.0 mL) using a cannula at 0 ꢀC. Subse- (t, 1H, J5,6a ¼ J5,6b ¼ 6.0 Hz, H-5), 4.05–4.00 (m, 2H, H-3, H-4),
quently, TMSOTf (54.0 mL, 0.298 mmol) was added to the 3.97 (dd, 1H, J2,3 ¼ 10.0 Hz, H-2), 3.73 (d, 2H, H-6a, H-6b); 13C
mixture at 0 ꢀC. Aer stirring for 0.5 h at the same temperature, NMR (125 MHz, CD3OD): d 137.1, 135.1, 127.1, 125.0, 119.6,
the completion of the reaction was conrmed by HPTLC (1 : 1 n- 114.1, 113.4, 112.7, 101.9, 73.4, 71.6, 71.0, 70.4, 62.7, 49.9.
hexane/EtOAc). The reꢀaction was quenched by the addition of HRMS (ESI-TOF): m/z calcd for C14H15BrClNO6: 429.9663 [M +
satd aq NaHCO3 at 0 C. The precipitate was ltered through Na]+; found: 429.9668.
Celite pad and the pad was washed with EtOAc. The combined
ltrate and washings were washed with satd aq NaHCO3, 2 M
HCl, and brine. The organic layer was subsequently dried over
Conflicts of interest
Na2SO4, ltered, and concentrated. The resulting residue was There are no conicts of interest to declare.
puried by silica gel column chromatography (9 : 1 n-hexane/
EtOAc) to give 19 (229 mg, 96%, a/b ¼ 20/1) as purple powder.
Acknowledgements
19a: 1H NMR (500 MHz, CDCl3): d 8.23 (d, 1H, 3Jortho ¼ 8.5 Hz,
Ar), 8.05–7.36 (m, 11H, Ar), 7.16 (s, 1H, ]CH–N), 5.96 (dd, 1H, This work was supported in part by JSPS KAKENHI Grant
J1,2 ¼ 3.5 Hz, J2,3 ¼ 10.5 Hz, H-2), 5.94 (d, 1H, H-1), 5.90 (dd, 1H, Number JP18K05455 (to A. I.). We thank Prof. Dr Thiem and Dr
¨
J3,4 ¼ 3.0 Hz, H-3), 5.03 (d, 1H, H-4), 4.35 (dd, 1H, J5,6a ¼ 2.0 Hz, Bottcher (University of Hamburg) for technical support on the
Jgem ¼ 13.0 Hz, H-6a), 4.22 (dd, 1H, J5,6b ¼ 1.5 Hz, H-6b), 4.10 (s, synthesis of indoxyl derivatives.
1H, H-5), 2.56 (s, 3H, Ac), 1.19 (s, 9H, tBu), 1.00 (s, 9H, tBu); 13
C
NMR (125 MHz, CDCl3): d 168.1, 166.2, 166.0, 140.2, 133.6,
133.5, 133.2, 130.6, 129.9, 129.7, 129.0, 128.5, 128.5, 128.4,
125.4, 122.3, 118.4, 116.2, 107.9, 97.5, 77.2, 70.9, 70.7, 68.3, 68.1,
66.8, 27.6, 27.4, 24.0, 23.3, 20.8. HRMS (ESI-TOF): m/z calcd for
Notes and references
1 J. A. Kiernan, Biotech. Histochem., 2007, 82, 73–103.
2 R. J. Barrnett and A. M. Seligman, Science, 1951, 114, 579–
582.
C
38H41BrClNO9Si: 820.1315 [M + Na]+; found: 820.1315.
5-Bromo-4-chloroindoxyl 4,6-O-di-tert-butylsilylene-a-D-gal-
3 (a) S. Saito, S. Sumita, Y. Kanda and Y. Sasaki, Tetrahedron
Lett., 1992, 33, 7381–7384; (b) S. Saito, S. Sumita, Y. Kanda
and Y. Sasaki, Chem. Pharm. Bull., 1994, 42, 1016–1027.
actopyranoside (20). To a solution of 19 (210 mg, 0.256 mmol, a/
b ¼ 20/1) in the mixed solvent (2.6 mL, 1 : 1 MeOH–THF) was
added sodium methoxide (1.0 M solution in MeOH, 77 mL, 76.8
¨
4 For review see: S. Bottcher and J. Thiem, Trends Carbohydr.
ꢀ
mmol) at 0 C. Aer stirring for 1.5 h at rt as the reaction was
Res., 2014, 6, 1–10 and references therein.
5 N-Acetyl-indoxyl acceptor is more likely present in the keto
form in non-polar and aprotic solvents, which was
conrmed in 1H NMR spectrum measured in this study
(see ESI†).
monitored by TLC (1 : 1 n-hexane/EtOAc), the reaction was
neutralized with Muromac (H+) resin. The resin was ltered off
and washed with MeOH. The ltrate and washings were
concentrated. The resulting residue was puried by silica gel
column chromatography (1 : 1 n-hexane/EtOAc) to give 20
(225 mg, 88%) as white powder. [a]D +106.7 (c 1.0 in CHCl3); 1H
NMR (500 MHz, CDCl3): d 7.87 (br s, 1H, NH), 7.37 (d, 1H, 3Jortho
¼ 8.5 Hz, Ar), 7.10 (d, 1H, JC]CH,NH ¼ 3.0 Hz, C]CH), 7.09 (d,
1H, Ar), 5.46 (d, 1H, J1,2 ¼ 3.0 Hz, H-1), 4.56 (d, 1H, J3,4 ¼ 1.5 Hz,
H-4), 4.30 (dd, 1H, J5,6a ¼ 2.0 Hz, Jgem ¼ 12.5 Hz, H-6a), 4.17 (dd,
1H, J5,6b ¼ 1.5 Hz, H-6b), 4.04–3.97 (m, 2H, H-2, H-3), 3.95 (s,
¨
´ ´
6 S. Bottcher, M. Hederos, E. Champion, G. Dekany and
J. Thiem, Org. Lett., 2013, 15, 3766–3769.
¨
7 (a) S. Bottcher and J. Thiem, Eur. J. Org. Chem., 2014, 564–
¨
574; (b) S. Bottcher and J. Thiem, RSC Adv., 2014, 4, 10856–
10861.
8 X. Wei, Q. Wu, J. Zhang, Y. Zhang, W. Guo, M. Chen, Q. Gu,
Z. Cai and M. Lu, Chem. Commun., 2017, 53, 103–106.
28246 | RSC Adv., 2019, 9, 28241–28247
This journal is © The Royal Society of Chemistry 2019