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. Author manuscript; available in PMC: 2018 Jun 7.
Published in final edited form as: J Am Chem Soc. 2017 May 22;139(22):7632–7639. doi: 10.1021/jacs.7b02988

Scheme 1.

Scheme 1

aReagents and conditions: (i) tBuNC (3.2 equiv), HOBt (10.2 equiv), DMA, room temperature (r.t.), 48 h. (ii) Piperidine (20 vol%), 30 min r.t.. (iii) PdCl2(dppf) (50 mol%), PhSiH3 (50 equiv), DMF, r.t. (iv) 6 M Gnd HCl, 0.2 M Na2HPO4, 0.2 M MPAA, 40 mM TCEP HCl, pH = 7.0, 6 h, r.t. (v) VA-044, tBuSH, TCEP, Gnd HCl buffer, 4 h, r.t. (vi) AgOAc (100 equiv), 70% aqueous AcOH, 2.5 h, r.t. (vii) 6 M Gnd HCl, 0.2 M Na2HPO4, pH = 7.0, 6 h, r.t.

bReagents and conditions: (viii) 6 M Gnd HCl, 0.2 M Na2HPO4, 0.2 M MPAA, 40 mM TCEP HCl, pH = 7.0, 4 h, r.t. (ix) NH2OMe HCl added, pH = 4.5−5.0, 4.5 h, r.t. (x) 6 M Gnd HCl, 0.2 M Na2HPO4, 0.2 M MPAA, 20 mM TCEP HCl, pH = 7.0, 6.5 h, r.t. (xi) TFA/thioanisole/ethanedithiol/anisole (90:5:3:2), 2 h, r.t. (xii) Solubilization in 1:1 MeCN/H2O (0.1% TFA) with sonication, then TCEP, pH = 8.0, and RP-HPLC purification; HOBt = 1-Hydroxybenzotriazole, DMA = N,N-dimethylacetamide, Gnd = guanidine, MPAA = 4-mercaptophenylacetic acid, TCEP = Tris(2-carboxyethyl)phosphine, VA-044 = 2,2′-Azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, TFA = trifluoroacetic acid. Yields are reported in the following manner: green = all-L-residue peptides; purple = all-D-residue peptides.