Scheme 2.

Total synthesis of orfamide A and its stereoisomers (see Table 1). Reagents and Conditions: a) piperidine/DMF (20 vol %); 14, HATU, HOAt, 2,4,6‐collidine, DMF, r.t.; b) Pd(PPh₃)₄, PhSiH₃, CH₂Cl₂, r.t.; c) HATU, HOAt, 2,4,6‐collidine, DMF, r.t.; d) DBU/piperidine/DMF (2 vol %, 2 vol %), 2×30 s; e) Fmoc‐A.A., HBTU, HOBt, DIEA, DMF, r.t.; piperidine/DMF (20 vol %); f) (R)‐ or (S)‐3‐TBSoxy tetradecanoic acid, HBTU, HOBt, DIEA, DMF, r.t.; g) 0.1 N HCl/HFIP, TIS (1 vol %), r.t.[ ²⁷ , ³⁰ ]