FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors

Scheme 1

Synthesis of FK228 analogues. Shown in the schematic are the steps, reagents, and conditions used for FK228 analogue synthesis. Compounds 1–7 are the intermediates during the synthesis. For steps 7a–f, the different R₁ and R₂ group substitutions were made to generate the various JMA analogues shown. Symbols: (a) NaBH₃CN; (b) Fmoc-Asp(OAl), DIC; (c) Piperidine; (d) Fmoc-AA₁, HBTU; (e) Fmoc-AA₂, HBTU; (f) Fmoc-D-Cys(Trt), HBTU; (g) Fmoc-D-Val, HBTU; (h) Pd(PPh₃)₄, DMBA; (i) HBTU; (j) 1% TFA; (k) I₂; (l) TFA (>95%).