Supporting Information (T. Yoshiya et al.)
Supporting Information
S-Acyl isopeptide method: use of allyl-type protective group
for improved preparation of thioester-containing S-acyl
isopeptides by Fmoc-based SPPS
Taku Yoshiya, Yuka Hasegawa, Wakana Kawamura, Hiroyuki Kawashima, Youhei
Sohma, Tooru Kimura, Yoshiaki Kiso*
Department of Medicinal Chemistry, Division of Medicinal Chemical Sciences, Center
for frontier Research in Medicinal Science, 21st Century COE program, Kyoto
Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
Fax: +81 75 591 9900
Tel: +81 75 595 4635
E-mail: kiso@mb.kyoto-phu.ac.jp
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Supporting Information (T. Yoshiya et al.)
Figure S1 HPLC profile of pure [D-Val]-2. Analytical HPLC was performed using a
C18 reverse phase column (4.6  150 mm; YMC Pack ODS AM302) with binary
solvent system: a linear gradient of CH3CN (0–100% CH3CN, 40 min) in 0.1% aqueous
TFA at a flow rate of 0.9 mL min–1 (40C), detected at 230 nm.
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Supporting Information (T. Yoshiya et al.)
Figure S2 HPLC profiles of (A) crude 1 derived from crude 2, (B) crude 1 + D-Val2
derivative and (C) crude 1 + D-Cys3 derivative. Analytical HPLC was performed using a
C18 reverse phase column (4.6  150 mm; YMC Pack ODS AM302) with binary
solvent system: a linear gradient of CH3CN (23–43% CH3CN, 40 min) in 0.1% aqueous
TFA at a flow rate of 0.9 mL min–1 (40 C), detected at 230 nm.
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Supporting Information (T. Yoshiya et al.)
Figure S3 HPLC profiles of (A) crude 22, (B) pure 22 and (C) pure 23 synthesized by
the conventional Fmoc-based SPPS. Non-peptidic compound was eluted at peak #.
HPLC conditions were similar to those described in Fig. S1.
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Supporting Information (T. Yoshiya et al.)
Figure S4 (A) S-Acyl isodipeptide unit 20. (B, C) Epimerization in the synthesis of 20
was evaluated by analytical RP-HPLC: (B) crude 20, (C) crude 20 + the authentic
D-allo-Thr
derivative. (D, E) HPLC profiles of (D) pure 20 and (E) pure [D-allo-Thr]-20.
HPLC conditions were similar to those described in Fig. S1.
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Supporting Information (T. Yoshiya et al.)
Figure S5 (A) S-Acyl isodipeptide unit 21. (B, C) Epimerization in the synthesis of 21
was evaluated by chiral HPLC: (B) crude 21, (C) crude 21 + the authentic D-Lys
derivative. Chiral HPLC was performed using Chiralcel® OD normal phase column (4.6
 250 mm; Daicel Chemical Ind., Ltd, Tokyo, Japan); mobile phase, n-hexane/ethanol
(32:1), 0.1% TFA; flow rate, 1.5 mL min-1 (room temperature), detected at 230 nm. (D,
E) HPLC profiles of (D) pure 21 and (E) pure [D-Lys]-21. HPLC conditions were
similar to those described in Fig. S1.
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Supporting Information (T. Yoshiya et al.)
Figure S6 Epimerization in the synthesis of 22 derived from crude isopeptide 17. HPLC
profile of (A) crude 22, (B) crude 22 + [D-allo-Thr6]-22. Analytical HPLC was
performed using a C18 reverse phase column (4.6  150 mm; YMC Pack ODS AM302)
with binary solvent system: a linear gradient of CH3CN (2–32% CH3CN, 40 min) in
0.1% aqueous TFA at a flow rate of 0.9 mL min–1 (40C), detected at 230 nm.
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Supporting Information (T. Yoshiya et al.)
Figure S7 Epimerization in the synthesis of 22 derived from crude isopeptide 18. HPLC
profile of (A) crude 22, (B) crude 22 + [D-allo-Thr6]-22. HPLC conditions were similar
to those described in Fig. S6.
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