Skip to main content
. 2022 Aug 25;144(37):16930–16952. doi: 10.1021/jacs.2c05499

Scheme 1. Synthesis of XL01126 and cis-XL01126.

Scheme 1

Reagents and conditions: (a) 2 N HCl in dioxane and dichloromethane (DCM) or DCM/methanol mix; (b) (2S,4S)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU), triethylamine (TEA), DCM; (c) Fmoc-S-trityl-l-penicillamine, HATU, TEA, dimethylformamide (DMF); (d) 1-fluorocyclopropane-1-carboxylic acid, HATU, TEA, DCM; (e) trifluoroacetic acid (TFA), triisopropylsilane, DCM, 0 °C; (f) 4 N HCl in 1,4-dioxane, 4-amino-3-methoxybenzoic acid, water, 100 °C; (g) hydroxybenzotriazole (HOBt), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI), N,N-diisopropylethylamine (DIPEA), 1-Boc-piperizine, DMF; (h) trans-1,4-bis(bromomethyl)cyclohexane, K2CO3, acetone, 50 °C; and (i) 5 or 10, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), tetrahydrofuran (THF).