Synthesis and biological activity of [Tic5] didemnin B.

A didemnin B analog containing a Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) as a conformationally restrained replacement for tyrosine has been synthesized and shown to have comparable potency as a protein biosynthesis inhibitor. Synthetic highlights include an oxidation of an alcohol to an acid in the presence of the sensitive Tic heterocycle and a modified Schmidt-type one-pot macrocyclization.

• Publication year

  1998

• Venue

  Bioorganic & Medicinal Chemistry Letters

• Publication date

  1998-12-15

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/S0960-894X(98)00662-3PMID 9934489
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Synthesis of methylated phenylalanines via hydrogenolysis of corresponding 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids. Synthesis and biological activity of oxytocin analogs with methylated phenylalanines in position 2.

  2009cited by this paper
• Phase I/II clinical trial of didemnin B in non-small-cell lung cancer: neuromuscular toxicity is dose-limiting

  2004cited by this paper
• Synthesis of a Reduced Ring Analog of Didemnin B

  1997cited by this paper
• Molecular design and bioorganic catalysis

  1996cited by this paper
• Didemnin binds to the protein palmitoyl thioesterase responsible for infantile neuronal ceroid lipofuscinosis.

  1996cited by this paper
• Synthesis and biological activities of [N-MeLeu5] didemnin B

  1996cited by this paper
• Structure−Activity Relationships of the Didemnins1,2

  1996cited by this paper
• Synthetic Routes to a Constrained Ring Analog of Didemnin B.

  1996cited by this paper
• Synthesis of (-)-2-Fluoroshikimic Acid.

  1996cited by this paper
• Analogs of the β-turn of the cyclodepsipeptide didemnin B

  1996cited by this paper
• Structure--activity relationships of the didemnins.

  1996cited by this paper
• Didemnin B induces cell death by apoptosis: the fastest induction of apoptosis ever described.

  1995cited by this paper
• Mechanism of protein synthesis inhibition by didemnin B in vitro.

  1995cited by this paper
• Synthesis of New Didemnin B Analogs for Investigations of Structure/Biological Activity Relationships

  1994cited by this paper
• GTP-dependent binding of the antiproliferative agent didemnin to elongation factor 1 alpha.

  1994cited by this paper
• Total synthesis of (-)-nummularine F

  1992cited by this paper
• Application of the allylic diazene rearrangement: synthesis of the enediyne-bridged tricyclic core of dynemicin A

  1992cited by this paper
• A specific binding site in Nb2 node lymphoma cells mediates the effects of didemnin B, an immunosuppressive cyclic peptide.

  1992cited by this paper
• Total synthesis and structural investigations of didemnins A, B, and C

  1990cited by this paper
• Conformational Analysis of Didemnins. A multidisciplinary approach by means of X-Ray, NMR, molecular-dynamics, and molecular-mechanics techniques

  1989cited by this paper
• Phase I clinical and pharmacokinetic investigation of didemnin B, a cyclic depsipeptide.

  1988cited by this paper
• Inhibition of T-lymphocyte proliferation by the cyclic polypeptide didemnin B: no inhibition of lymphokine stimulation.

  1988cited by this paper
• Crystal and molecular structure of didemnin B, an antiviral and cytotoxic depsipeptide.

  1988cited by this paper
• In vivo effect of didemnin B on two tumors of the rat.

  1987cited by this paper
• DIDEMNIN B–AN IMMUNOSUPPRESSIVE CYCLIC PEPTIDE THAT STIMULATES MURINE HEMAGGLUTINATING ANTIBODY RESPONSES AND INDUCES LEUKOCYTOSIS IN VIVO

  1987cited by this paper
• Selective oxidation of aldehydes to carboxylic acids with sodium chlorite-hydrogen peroxide

  1986cited by this paper
• Biologically active peptides and their mass spectra

  1982cited by this paper
• A Novel Method for Preparation of Ansapeptides; Synthesis of Model Peptide Alkaloids

  1981cited by this paper
• Synthesis of Dihydrozizyphin G

  1981cited by this paper
• Structures of the didemnins, antiviral and cytotoxic depsipeptides from a Caribbean tunicate

  1981cited by this paper
• Synthetic studies toward verrucarol. 2. Synthesis of the AB ring system

  1980cited by this paper

• New approaches towards the synthesis of 1,2,3,4-tetrahydro isoquinoline-3-phosphonic acid (TicP)

  2021cites this paper
• Conformational Changes in Tyrosine 11 of Neurotensin Are Required to Activate the Neurotensin Receptor 1.

  2020cites this paper
• Chapter 4 – Macrocyclic N-Methylated Cyclic Peptides and Depsipeptides

  2015cites this paper
• Diversity-oriented synthesis of medicinally important 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) derivatives and higher analogs.

  2014cites this paper
• Ascidians (Tunicates)–2

  2014cites this paper
• Diversity-oriented approaches to unusual α-amino acids and peptides: step economy, atom economy, redox economy, and beyond.

  2013cites this paper
• Didemnins, tamandarins and related natural products.

  2012cites this paper
• Applications and modifications of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) in peptides and peptidomimetics design and discovery.

  2010cites this paper
• Total synthesis and biological evaluation of tamandarin B analogues.

  2007cites this paper
• Synthesis and biological evaluation of tamandarin B analogues.

  2006cites this paper
• Preparation and tumor affinity testing of the radioiodinated tetrahydroisoquinoline derivative [123I]TIC(OH) for targeting prostate cancer.

  2006cites this paper
• Natural products as probes of cell biology: 20 years of didemnin research

  2002cites this paper
• Total syntheses of conformationally constrained didemnin B analogues. replacements of N,O-dimethyltyrosine with L-1,2,3,4-tetrahydroisoquinoline and L-1,2,3,4-tetrahydro-7-methoxyisoquinoline.

  2001cites this paper
• Preparation and investigation of tumor affinity, uptake kinetic and transport mechanism of iodine-123-labelled amino acid derivatives in human pancreatic carcinoma and glioblastoma cells.

  2001cites this paper
• Total syntheses and biological investigations of tamandarins A and B and tamandarin A analogs.

  2001cites this paper
• Total synthesis of a conformationally constrained didemnin B analog.

  2001cites this paper
• Inhibition of protein synthesis by didemnins: cell potency and SAR.

  2000cites this paper
• Stereoselective synthesis of 3-mono- and 1,3-disubstituted 4-phenyl-1,2,3,4-tetrahydroisoquinolines

  2000cites this paper