*3.6. Synthesis of Talarolide B*

3.6.1. Coupling of the First Amino Acid

After swelling the 2-CTC resin for 20 min in dry CH2Cl2 (2 mL), a solution of Fmoc-Gly-OH (1.2 eq.) and DIPEA (44 μL, 0.25 mmol, 2.5 eq.) in dry CH2Cl2 (2 mL) was added to the resin and mixed for 2 h. The resin was filtered, then MeOH (200 μL) was added and mixed for 15 min to cap the resin. The resin was washed with dry CH2Cl2 (5 × 1 min), 1:1 CH2Cl2/MeOH (5 × 1 min) and MeOH (2 × 1 min).

### 3.6.2. Elongation of Peptide Sequence

Amino acid activation was achieved by dissolving an Fmoc-amino acid (0.32 mmol, 3.2 eq.) in a 0.4 M HATU/DMF solution (0.75 mL, 0.3 mmol, 3.0 eq.), followed by the addition of DIPEA (105 μL, 0.6 mmol, 6.0 eq.). The coupling cycle consisted of Fmoc deprotection with 20% of piperidine in DMF (twice, 5 and 10 min), and a 5 min DMF flow-wash followed by coupling with preactivated Fmoc-amino acid (3.2 eq.) over 2 × 30 min, or 2 × 3 h for coupling of Fmoc-amino acids to sterically hindered *N*-Meamino acids. Upon completion of the synthesis the resin was washed with DMF, CH2Cl2, and MeOH, then dried (vacuum desiccator) as described above in the synthesis of the dipeptides.
