PMID- 23989475
OWN - NLM
STAT- MEDLINE
DCOM- 20140408
LR  - 20130830
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 4
DP  - 2013
TI  - The first total synthesis of the cyclodepsipeptide pipecolidepsin A.
PG  - 2352
LID - 10.1038/ncomms3352 [doi]
AB  - 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 gamma-branched beta-hydroxy-alpha-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.
FAU - Pelay-Gimeno, Marta
AU  - Pelay-Gimeno M
AD  - 1] Institute for Research in Biomedicine, Baldiri Reixac 10, 08028 Barcelona, 
      Spain [2] CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and 
      Nanomedicine, Barcelona Science Park, 08028 Barcelona, Spain.
FAU - Garcia-Ramos, Yesica
AU  - Garcia-Ramos Y
FAU - Jesus Martin, Maria
AU  - Jesus Martin M
FAU - Spengler, Jan
AU  - Spengler J
FAU - Molina-Guijarro, Jose Manuel
AU  - Molina-Guijarro JM
FAU - Munt, Simon
AU  - Munt S
FAU - Francesch, Andres M
AU  - Francesch AM
FAU - Cuevas, Carmen
AU  - Cuevas C
FAU - Tulla-Puche, Judit
AU  - Tulla-Puche J
FAU - Albericio, Fernando
AU  - Albericio F
LA  - eng
SI  - PubChem-Substance/163826383
SI  - PubChem-Substance/163826384
SI  - PubChem-Substance/163826385
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Depsipeptides)
RN  - 0 (Pipecolic Acids)
RN  - 0 (pipecolidepsin A)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Depsipeptides/chemical synthesis/chemistry/*pharmacology
MH  - Female
MH  - HT29 Cells
MH  - Hep G2 Cells
MH  - Humans
MH  - MCF-7 Cells
MH  - Male
MH  - Neoplasms/*drug therapy
MH  - Pipecolic Acids/chemical synthesis/chemistry/*pharmacology
MH  - Porifera/metabolism
MH  - Structure-Activity Relationship
EDAT- 2013/08/31 06:00
MHDA- 2014/04/09 06:00
CRDT- 2013/08/31 06:00
PHST- 2013/04/28 00:00 [received]
PHST- 2013/07/24 00:00 [accepted]
PHST- 2013/08/31 06:00 [entrez]
PHST- 2013/08/31 06:00 [pubmed]
PHST- 2014/04/09 06:00 [medline]
AID - ncomms3352 [pii]
AID - 10.1038/ncomms3352 [doi]
PST - ppublish
SO  - Nat Commun. 2013;4:2352. doi: 10.1038/ncomms3352.