Pipecolidepsin A is a head-to-side-chain cyclodepsipeptide isolated from the marine sponge Homophymia lamellosa. This compound shows relevant cytotoxic activity in three human tumour cell lines and has unique structural features, with an abundance of non-proteinogenic residues, including several intriguing amino acids. Although the moieties present in the structure show high synthetic difficulty, the cornerstone is constituted by the unprecedented and highly hindered g-branched b-hydroxy-a-amino acid D-allo-(2R,3R,4R)-2-amino-3-hydroxy-4,5-dimethylhexanoic acid (AHDMHA) residue, placed at the branching ester position and surrounded by the four demanding residues L-(2S,3S,4R)-3,4-dimethylglutamine, (2R,3R,4S)-4,7-diamino-2,3-dihydroxy-7-oxoheptanoic acid, D-allo-Thr and L-pipecolic acid. Here we describe the first total synthesis of a D-allo-AHDMHA-containing peptide, pipecolidepsin A, thus allowing chemical structure validation of the natural product and providing a robust synthetic strategy to access other members of the relevant head-to-side-chain family in a straightforward manner.

Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond formation, in which the N‐hydroxylamine group is replaced by a potassium salt. The complete suppression of its acidity converts K‐Oxyma into the most suitable coupling choice when peptides are assembled on highly acid‐labile solid‐supports. The coupling efficiency and diminished prospects for epimerization are conserved relative to OxymaPure. In addition, K‐Oxyma displays excellent solubility in a variety of organic solvents and undergoes safer decomposition than classical 1‐hydroxybenzotriazole additives.

The palladium(0) complexes of (E,E,E)‐1,6,11‐tris(arenesulfonyl)‐1,6,11‐triazacyclopentadeca‐3,8,13‐trienes deliver palladium to phosphanes with the generation of high concentrations of catalytically active species such as Pd(PPh3)2. After oxidation of the phosphanes, the palladium is reincorporated into the macrocycle, thus avoiding agglomeration and precipitation. These conclusions were reached by 31P NMR, 19F NMR, and electrospray ionization mass spectrometry studies of telomerization and Tsuji−Trost reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)