- Combinatorial Solid-Phase Synthesis and Biological Evaluation of Cyclodepsipeptide Destruxin B as a Negative Regulator for Osteoclast Morphology
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Combinatorial synthesis and biological evaluation of cyclodepsipeptide destruxin B have been achieved. The cyclization precursors were prepared by solid-phase peptide synthesis via a split and pool method utilizing SynPhase lanterns with colored tags and cogs, followed by cleavage from the polymer-support. Macrolactonization utilizing MNBA-DMAPO in solution-phase was successfully performed in parallel to afford the desired 64-member destruxin analogues in moderate to good yields. Biological evaluation of the synthesized analogues indicated that a MeAla residue for the building block A is required to induce the desired morphological changes in osteoclast-like multinuclear cells (OCLs), and introduction of the substituent at the R4 position of a proline moiety is tolerated by the morphology and may enable the preparation of a molecular probe for the target identification in the osteoclasts.
- Sato, Hiroshi,Yoshida, Masahito,Murase, Hayato,Nakagawa, Hiroshi,Doi, Takayuki
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supporting information
p. 590 - 595
(2016/11/03)
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- Probing host-selective phytotoxicity: Synthesis of destruxin B and several natural analogues
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The syntheses of the host-selective phytotoxin destruxin B [cyclo(βAla-Hmp-Pro-Ile-MeVal-MeAla), Hmp = (2R)-2-hydroxy-4-methylpentanoic acid], and the closely related natural analogues homodestruxin B (MeVal→MeIle), desmethyldestruxin B (MeVal→Val), hydroxydestruxin B (Hmp→Dhmp, Dhmp = (2R)-2,4-dihydroxy-4-methylpentanoic acid), and hydroxyhomodestruxin B (MeVal→MeIle, Hmp→Dhmp) are described. In each case, the MeAla-βAla linkage was formed by cyclization and the precursor linear hexadepsipeptides were formed by condensing two three-residue fragments. Radiolabeled samples of destruxin B, homodestruxin B, and hydroxydestruxin B were prepared by coupling [3-14C]-β-alanine to the appropriate pentadepsipeptide followed by cyclization. A noteworthy feature of the synthesis involves the novel use of a Boc-hydrazide protecting group on dipeptides with a C-terminal N-methylalanine residue to inhibit the otherwise facile dioxopiperazine formation during peptide coupling.
- Ward,Gai,Lazny,Pedras
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p. 7832 - 7840
(2007/10/03)
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- Synthesis of the host-selective phytotoxin destruxin B. Avoiding diketopiperazine formation from an N-methyl amino acid dipeptide by use of the Boc-hydrazide derivative
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An efficient synthesis of the cyclic hexdepsipeptide destruxin B from its component residues is described that involves a [3+3] fragment coupling followed by cyclization via the azide method. A novel feature of the synthesis is the use of the Boc-hydrozide protecting group for the C-terminal N-methylalanine residue. This group serves bath to inhibit facile diketopiperazine formation from the N-methylvalyl-N-methylalanine dipeptide and as a latent activating group for hexadepsipeptide cyclization.
- Ward, Dale E.,Lazny, Ryszard,Soledade,Pedras
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p. 339 - 342
(2007/10/03)
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