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Acknowledgments
We are indebted to Mr. John Harman, Mr. Chris
DeVore, and Mr. Shawn Ayube for LC–MS support.
We also wish to thank Ms. Monica Mistry, Mr. Jason
Haelewyn, and Mr. Rajesh Huntley for pharmacology
support and Dr. John Saunders for valuable discussions.
This work was partly supported by NIH Grant 2-R44-
DK059107-02.
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6. (3S)-(À)-1-Benzyl-3-(methylamino)pyrrolidine is commer-
cially available from Tokyo Chemical Industry (TCI)
America, Portland, Oregon. The e.e. was determined to be
>97%.
7. (3R)-(À)-1-Benzyl-3-aminopyrrolidine is commercially
available from Tokyo Chemical Industry (TCI) America,
Portland, Oregon (e.e. 98%).
8. Typical experimental procedure for preparation of rAPUs
via mesylate displacement: synthesis of 23c. To a solution
of the mesylate 22 (30 mg, 0.06 mmol) in DMA (0.5 mL)
was added piperidine (100 lL, 1 mmol). The reaction
mixture was heated at 60 ꢁC for 20 h then cooled to room
temperature. The mixture was diluted to 1 mL with
methanol and purified by preparative HPLC. Concentra-
tion of the pure fractions in vacuo afforded the TFA salt
of 23c (32 mg, 90%) as a colorless oil: 1H NMR
(CDCl3 + one drop CD3OD) d 7.59 (d, 2H, J = 8.1 Hz),