# Cyclic Octamer Petroids: Simplified Isosters of Bioactive Fungal Cyclodepsipeptides
## 3 Experimental Section
### Chemistry
#### 3.1.3 General Procedure for the High Dilution Cyclization. Synthesis of Cyclic Peptoids **5-8**  
The solutions of the linear peptoids (0.150 mmol), previously co-evaporated three times with toluene, were prepared under nitrogen in dry DCM (5.0 mL). The mixture was added dropwise to a stirred solution of HATU (0.171 g, 0.450 mmol) and DIPEA (104 uL, 0.600 mmol) in dry DMF (45.0 mL) by a syringe pump in 5 h, at room temperature in anhydrous atmosphere. After 12 h the resulting mixture was concentrated _in vacuo_, diluted with CH\({}_{2}\)Cl\({}_{2}\) (30 mL) and washed with a solution of HCl (1.0 M, 15 mL). The aqueous phase was then extracted again with 30 mL of CH\({}_{2}\)Cl\({}_{2}\). The organic phases were washed with water (60.0 mL), dried over anhydrous MgSO\({}_{4}\), filtered and concentrated _in vacuo_. The cyclic peptoids were dissolved in 50% acetonitrile in HPLC grade water and analysed by RP-HPLC; purity > 90% conditions: 5-100% A in 30 min (A, 0.1% TFA in acetonitrile, B, 0.1% TFA in water); flow: 1 mL min\({}^{-1}\), 220 nm. The crude cyclic peptoids **5**, 7 were dissolved in hot acetonitrile and precipitated by slowly cooling the acetonitrile solutions. The crude **6**, **8** were purified on reverse silica gel (C\({}_{18}\)); conditions: 10-100% A (A: acetonitrile; B: water). **5**: white amorphous solid, 0.027 g, yield: 21%; \(t_{R}\): 12.1 min. \({}^{1}\)H-NMR (400 MHz, CDCl\({}_{3}\), \(c\) stands for _cis_ amide bond, \(t\) stands for _trans_ amide bond) 8: 4.77 (2H, m, N-CH(CH\({}_{3}\))\({}_{2}\), \(c\)), 4.74 (2H, d, J 16.1 Hz, O=C-CHH-N-iBu, \(t\)), 4.32 (2H, d, J 17.8 Hz, O=C-CHH-N-iPr, \(c\)), 4.39 (2H, d, J 17.7 Hz, O=C-CHH-N-iPr, \(c\)), 3.69 (2H, d, J 17.8 Hz, O=C-CHH-N-iPr, \(c\)), 3.87 (m, 2H, N-CH(CH\({}_{3}\))\({}_{2}\), \(t\)), 3.64 (2H, dd, J 14.1, 7.4 Hz, N-CHH-CH(CH\({}_{3}\))\({}_{2}\), \(c\)), 3.60 (4H, d, O=C-CHH-N-iBu, \(t\) and O=C-CHH-N-iBu, \(c\), overlapping), 3.51 (2H, d, J 17.7 Hz, O=C-CHH-N-iPr, \(t\)), 3.22 (2H, dd, J 13.9, 5.0 Hz, N-CHH-CH(CH\({}_{3}\))\({}_{2}\), \(t\)), 3.09 (2H, dd, J 13.9, 5.0 Hz, N-CHH-CH(CH\({}_{3}\))\({}_{2}\), \(t\)), 2.68 (2H, dd, J 14.1, 7.4 Hz, N-CHH-CH(CH\({}_{3}\))\({}_{2}\), \(c\)), 1.87 (4H, m, N-CH\({}_{2}\)-CH(CH\({}_{3}\))\({}_{2}\), \(c\)) and 1), 1.21 (6H, d, J 6.7 Hz, N-CH(CH\({}_{3}\))\({}_{2}\), \(t\)), 1.14 (6H, d, J 6.7 Hz, N-CH(CH\({}_{3}\))\({}_{2}\), \(t\)), 1.14 (6H, d, J 6.7 Hz, N-CH(CH\({}_{3}\))\({}_{2}\), \(c\)), 1.11 (6H, d, J 6.7 Hz, N-CH(CH\({}_{3}\))\({}_{2}\), \(t\)), 1.05 (6H, d, J 6.7 Hz, N-CH(CH\({}_{3}\))\({}_{2}\), \(c\)), 0.98 (12H, d, J 6.5 Hz, N-CH\({}_{2}\)-CH(CH\({}_{3}\))\({}_{2}\), \(c\)) and 1), 0.91 (6H, d, J 6.5 Hz, N-CH\({}_{2}\)-CH(CH\({}_{3}\))\({}_{2}\), \(c\)), 1.3C-NMR (100 MHz, CDCl\({}_{3}\)) 8: 170.3 (x2), 169.4 (x2), 169.3 (x2), 166.1 (x2), 56.2 (x2), 55.8 (x2), 50.6 (x2), 49.0 (x2), 48.0 (x2), 45.6 (x2), 43.2 (x2),42.8 (x2), 27.8 (x2), 27.0 (x2), 20.9 (x2), 20.6 (x3), 20.4 (x3), 19.9 (x4), 19.6 (x2), 19.6 (x2). HR-ESI-MS \(m/z\): 849.6170 [M + H]\({}^{+}\) (calcalcd. for C\({}_{44}\)H\({}_{81}\)N\({}_{8}\)O\({}_{8}\)\({}^{+}\), 849.6172). **6**: white amorphous solid, 0.041 g, yield: 31%; \(t_{R}\): 12.6 min.