G
C.-H. Wu et al.
Letter
Synlett
(10) (a) Skipski, V.; Peterson, R.; Barclay, M. Biochem. J. 1964, 90, 374.
(b) Rouser, G.; Fleischer, S.; Yamamoto, A. Lipids 1970, 5, 494.
(c) Staneck, J. L.; Roberts, G. D. Appl. Microbiol. 1974, 28, 226.
(d) Minnikin, D. E.; Hutchinson, I. G.; Caldicott, A. B.;
Goodfellow, M. J. Chromatogr. A 1980, 188, 221.
column chromatography [silica gel, hexane–EtOAc (3:1 for 4b,
4:1 for 4c, 1:2 for 5)]. 4b was obtained as a colorless oil; yield:
34 mg (90%). 4c was also obtained as a colorless oil; yield: 12
mg (31%). 4d was not obtained. Eluting solvent for TLC: hexane–
EtOAc (1:1 for 4b, 2:1 for 4c and 4d).
(11) Eller, S.; Collot, M.; Yin, J.; Hahm, H. S.; Seeberger, P. H. Angew.
Chem. Int. Ed. 2013, 52, 5858.
(12) (a) Huang, X.; Huang, L.; Wang, H.; Ye, X.-S. Angew. Chem. 2004,
116, 5333. (b) Verma, V. P.; Wang, C.-C. Chem. Eur. J. 2013, 19,
846.
(17) Solid-Phase Syntheses of Aminopentyl Esters 7a–c
A solution of the appropriate amino acid 6a–c (0.5 mmol) and
HOBt (68 mg, 0.5 mmol) in DMF (200 μL) was injected into
CH2Cl2 (4 mL) containing swollen resin 1 (500 mg, 0.1 mmol/g).
A solution of DIC (63 mg, 0.5 mmol) in DMF (200 μL) was
dropped into the reaction mixture, followed by the addition of a
catalytic amount of DMAP. The microwave-assisted reactions
were conducted at 90 °C for 20 min. Unreacted reagents were
washed out five times with CH2Cl2 and MeOH. The resin in
CH2Cl2 were exposed to UV radiation for 1 h, then filtered. The
products in the filtrate were purified by flash column chroma-
tography [silica gel, hexane–EtOAc (2:1 for 7a, 3:1 for 7b, 4:1 for
7c)]. 7a was obtained as white solid; yield: 19 mg (60%). 7b was
obtained as a colorless oil; yield: 32 mg (93%). 7c was obtained
as a colorless oil; yield 29 mg (82%). Eluting solvent for TLC:
hexane–EtOAc (1:2 for 7a, 1:1 for 7b and 7c).
(13) Solid-Phase Glycosylation Procedure for the Synthesis of Gly-
coside 4a
Resin 1 (500 mg, 0.1 mmol/g) was swollen in CH2Cl2 (4 mL) for 2
h. Swollen 1 in CH2Cl2 was mixed with sugar 2a (139 mg, 0.3
mmol) and TolSCl (38 μL, 0.3 mmol), then AgOTf (64 mg, 0.3
mmol) was added and the mixture was kept at r.t. for 3 h. Unre-
acted reagents were removed by sequential washing with
CH2Cl2 and MeOH (×3). The resins in CH2Cl2 were exposed to UV
radiation for 1 h, then filtered. The products in the filtrate were
purified by flash column chromatography [silica gel, hexane–
EtOAc (3:1 for 4a; 1:2 for 5)] to give 4a as a white solid; yield:
19 mg (56%). Linker 5 was also obtained as a white solid: yield:
5 mg (40%). Eluting solvent for TLC: hexane–EtOAc (1:1).
(14) Real-Time Analyses of Solid-Phase Reactions by TLC; General
Procedure
(18) Pathigoolla, A.; Pola, R. P.; Sureshan, K. M. Appl. Catal., A 2013,
453, 151.
(19) Triazole 11 by Solid-Phase Click Reaction
A mixture of resin 1 (500 mg, 0.1 mmol/g) swollen in DMF (2
mL) was slowly added to a 60% dispersion of NaH (50 mg, 0.6
mmol) in mineral oil at 0 °C, and the mixture was stirred at 0 °C
for 6 h. Propargyl bromide (54 μL, 0.6 mmol) was then slowly
added at 0 °C, and the mixture was kept at r.t. for 6 h. Unreacted
reagents were washed out five times with 1:1 v/v MeOH–H2O
and CH2Cl2. The resulting resin 8 was swollen in CH2Cl for 2 h. A
mixture of resin 8 in 2:2:1 CH2Cl2–MeCN–H2O (2 mL) was
treated with azide 9 (79 μL, 0.6 mmol) and CuSO4·5H2O (154
mg, 0.6 mmol), and the mixture was kept at r.t. for 3 h.
N2H4·H2O (30 μL, 0.6 mmol) was added, and the mixture was
allowed to react for 4 h. Unreacted reagents were washed out
five times with CH2Cl2 and MeOH. A mixture of the resin and
CH2Cl2 was exposed to a UV lamp for 1 h then filtered. The fil-
trate was purified by flash column chromatography [silica gel,
hexane–EtOAc (5:1)] to give 11 as a brown solid; yield: 9 mg
(43% over three steps). Eluting solvent for TLC: hexane–EtOAc
(2:1).
A minute sample of the reaction mixture in the reaction vessel
was captured by capillary attraction in a capillary tube (see
Supporting Information, Figure S1). The liquid solution in the
capillary was absorbed by using a TLC plate, while the resin
beads were retained in the capillary (Figure S2). The beads were
then washed sequentially with CH2Cl2 and MeOH three times to
remove excess reactants. Both CH2Cl2 and MeOH were able to
flow into the capillary through capillary attraction, and could
be subsequently removed by absorption onto the TLC plate.
After the repeated washing steps, the capillary loaded with the
beads and CH2Cl2 was irradiated with UV radiation for 10–15
minutes, and the resulting reaction mixture from the capillary
was spotted onto another TLC plate. After eluting the sample,
the TLC plate was stained with Hanessian’s reagent and heated
on a hotplate.
(15) Determination of the Reaction Time for Photocleavage
Resin 1 (500 mg, 0.1 mmol/g) was immersed in CH2Cl2 (7.8 mL)
for 1 h. Nine 0.1 mL aliquots were extracted from the resin solu-
tion and exposed to UV radiation (254 nm) for various times (5,
10, 15, 20, 30, 40, 60, 90, or 120 min). Linker 5, obtained after
irradiation and the removal of CH2Cl2, was dissolved in CD2Cl2
(0.4 mL) containing (5 × 10–6)% TMS (v/v) as an internal stan-
dard. The results are given in the Supporting Information
(Figure S3).
(20) Products 15a and 15b by Sequential Solid-Phase Reactions
A 1 M soln of TBAF in THF (500 μL, 0.5 mmol) was added drop-
wise to a solution of swollen resin 12 (500 mg, 0.1 mmol/g) in
CH2Cl2, and the mixture was stirred at r.t for 4 h. Unreacted
reagents were washed out with CH2Cl2 and MeOH to give resin
13. Resin 13 and a solution of glucopyranoside 2c (323 mg,
0.5 mmol) in CH2Cl2 were mixed with 1-(phenylsulfinyl)piperi-
dine (105 mg, 0.5 mmol) and Tf2O (82 μL, 0.5 mmol), and the
mixture was stirred at –78 °C for 2–3 h. Unreacted reagents
were washed out with CH2Cl2 and MeOH to give resin 14, which
was exposed to a UV lamp for 1 h. The filtrate was purified by
flash column chromatography [silica gel, hexane–EtOAc (7:1 for
15a, 6:1 for 15b)]. 15a was obtained as a colorless oil; yield
25 mg (50% overall). 15b was also obtained as a colorless oil;
yield 33 mg (66%). Eluting solvent for TLC: hexane–EtOAc (1:1).
(16) Solid-phase Glycosylation to Give Products 4b–d; General
Procedure
Swollen resin 1 (500 mg, 0.1 mmol/g) in CH2Cl2 was mixed with
the appropriate sugar derivate 2b–d (0.3 mmol) and NIS (56 mg,
0.3 mmol). TfOH (22 μL, 0.3 mmol) was added at –40 °C, and the
mixture was maintained at –40 °C for 2–3 h. All unreacted
reagents were washed out three times with CH2Cl2 and MeOH.
The resins in CH2Cl2 were exposed to UV radiation for 1 h then
filtered. The products in the filtrate were purified by flash
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–G