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. 2021 Jan 26;143(5):2423–2432. doi: 10.1021/jacs.0c13059

Scheme 1. Synthesis of the Inhibitors and ABPs Subject of the Here-Described Studies.

Scheme 1

Reagents and conditions. (a) For 6a and 18: 4a, TfOH (1.5 equiv), DMF, DCM, 4 Å molecular sieves, −20 to 0 °C, 6a 96%, 18 57%. For 6b: 4b, NIS, TfOH (1.5 equiv), DMF, DCM, 4 Å molecular sieves, 0 °C, 88%. For 6c: 4c, NIS, TfOH (1.5 equiv), DMF, DCM, 4 Å molecular sieves, 0 °C, 87%. (b) DDQ, DCM/H2O (19/1), rt, 7a 80%, 7b 74%, 7c 71%; (c) (i) mCPBA, DCM, 0 °C to rt; (ii) TBSCl, DMAP, imidazole, DCM, rt, 8a 20%, 9a 58%, 8b 21%, 9b 65%, 8c 22%, 9c 63%; (d) TBAF, THF, rt, 10a 90%, 10b 87%, 12a 91%, 12b 88%; (e) Pd(OH)2/C, H2, MeOH/H2O/dioxane (2/1/2), rt, 1a 100%, 3a 89%; (f) polymer-bound PPh3, MeCN, H2O, 70 °C, 79%; (g) Pd(OH)2/C, H2, HOAc, tBuOH/H2O/dioxane (1/2/1), rt, 91%; (h) Cy5-OSu or biotin-OSu, DIPEA, DMF, rt, 1c 33%, 1d 16%, 2b 10%, 2c 17%; (i) BnBr, NaH, TBAI, DMF, 0 °C to rt, 13a 82%, 13b 75%; (j) (i) NaN3, LiClO4, DMF, 100 °C; (ii) polymer-bound PPh3, MeCN, 60 °C, 14a 48%, 14b 42%; (k) 8-azidooctyltrifluoromethanesulfonate, DIPEA, DCM, 0 °C to rt, 15a 90%, 15b 88%; (l) Na, NH3 (liq.), tBuOH, THF, −60 °C, 2a 79%, 16 94%; (m) NaOMe, DCM/MeOH (1/1), rt, 93%; (n) (i) SOCl2, TEA, DCM, 0 °C; (ii) RuCl3·3H2O, NaIO4, EtOAc/ACN/H2O (2/2/1), 0 °C, 58%.