Peptide Thioacylation with High Stereochemical Preservation

Total Synthesis of the Cyclodepsipeptide Apratoxin A and Its Analogues and Assessment of Their Biological Activities

“…To solve this problem, we also tried to prepare 24 a through in situ generation of active thiono ester by a procedure reported by Hoeg-Jensen and co-workers. [18] Unfortunately, although this method did give some 24 b, the coupling yield was low, with the major product being amide 22 b (Scheme 5). Scheme Having failed in the above attempts, we turned our attention to the assembly of the thiazoline intermediate by a tandem deprotection/cyclodehydration strategy reported by Kelly and co-workers.…”

“…Many existing methods were tried without success for this special case: Wipf's thiolysis/cyclodehydration strategy,17 for example, failed to give thioamide 24 a because of Michael addition of H 2 S to the α,β‐unsaturated ester moiety. To solve this problem, we also tried to prepare 24 a through in situ generation of active thiono ester by a procedure reported by Hoeg‐Jensen and co‐workers 18. Unfortunately, although this method did give some 24 b , the coupling yield was low, with the major product being amide 22 b (Scheme ).…”

Nine‐Step Total Synthesis and Biological Evaluation of Rhizonin A

“…However, no desired product was observed when the reaction was performed in the presence of 2‐bromo‐1‐ethyl‐pyridinium tetrafluoroborate (BEP) [ 13 ] (entry 1) or 2,4,6‐trichlorobenzoyl chloride (TCBC) [ 14 ] (entry 2). Trace amount of heptapeptide 13 was produced as detected by MS spectra (entries 3—8) when the reaction was carried out using (7‐azabenzo‐triazol‐1‐yloxy)tris(pyrrolidino)phosphonium hexafluorophosphate (PyAOP), [ 15 ] 1‐ethyl‐ 3‐[3‐(dimethylamino)‐propyl]carbodiimide monohydrochloride (EDCI), [ 16 ] propylphosphonic acid anhydride (T 3 P), [ 17 ] diphenyl phosphorazidate (DPPA), [ 18 ] bis(2‐oxo‐3‐oxa‐zolidinyl)phosphinic chloride (BOP‐Cl), [ 19 ] and 2‐methyl‐6‐nitrobenzoic anhydride (MNBA) [ 20 ] as coupling reagents. Fragment coupling in the presence of either HATU/HOAt (entry 9, 8%) or T 3 P in DCM/DMF at 50 o C (entry 9, 10%) gave the desired coupling product 13 in a disappointingly low yield (Table 1).…”

Formal Synthesis of Kanamienamide

“…Considerable experimentation was needed to optimize the yield of the macrolactamization to give 14a, and the important results are summarized in Table 1. An extensive screening was conducted of condensing agents, including the carbodiimide reagents N,N′-dicyclohexylcarbodiimide 15a (DCC; Table 1, entry 1) and 1 -ethyl-3-[3-(dimethylamino)propyl]carbodiimide monohydrochloride 15b (EDCI; entry 2); the benzotriazole-based uronium salt 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b] pyridinium 3oxide hexafluorophosphate 16 (HATU, entry 3); the imidazolium-type reagent 2-chloro-1,3-dimethylimidazolinium hexafluorophosphate 17 (CIP; entry 4); the pyridinium reagents 2-bromo-1-ethylpyridinium tetrafluoroborate 18a (BEP; entry 7) and 2-chloro-1-methylpyridinium iodide 18b (CMPI; entry 8); the phosphonium-based reagent (7-azabenzotriazol-1-yloxy)tris(pyrrolidino)phosphonium hexafluorophosphate 19 (PyAOP; entry 9); and the phosphonic acid derivatives pentafluorophenyl diphenylphosphinate 20 (FDPP; entry 5), 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one 21 (DEPBT; entry 6), and bis(2-oxo-3-oxazolidinyl)phosphinic chloride 22 (BOP-Cl; entry 10). The reactions (entries 1-10) were performed in highly dilute solutions in DMF for 24 hours.…”