Alkaloid combinatorial synthesis

Combinatorial Synthesis of Alkaloid-like Compounds In Search of Chemical Probes of Protein-Protein Interactions... 

Wu and Sun have presented a versatile procedure for the liquid-phase synthesis of 1,2, ,4-tctrahydro-/i-carbolines [77]. After successful esterification of the MeO-PEG-OH utilized with Fmoc-protected tryptophan, one-pot cyclocondensations with various ketones and aldehydes were performed under microwave irradiation (Scheme 7.68). The desired products were released from the soluble support in good yields and high purity. The interest in this particular scaffold is due to the fact that the l,2,3,4-tetrahydro-/f-carboline pharmacophore is known to be an important structural element in several natural alkaloids, and that the template possesses multiple sites for combinatorial modifications. The microwave-assisted liquid-phase protocol furnished purer products than homogeneous protocols and product isolation/ purification was certainly simplified. 

Ley SV, Baxendale IR (2002b) New tools and concepts for modern organic synthesis. Nat Rev Drug Disc 1 573-586 Ley S V, Massi A (2000) J Comb Chem Polymer supported reagents in synthesis preparation of bicyclo[2.2.2]octane derivatives via tandem michael addition reactions and subsequent combinatorial decoration. 2 104—107 Ley SV, Schucht O, Thomas AW, Murray PJ (1999) Synthesis of the alkaloids ( )-oxomaritidine and ( )-epimaritidine using an orchestrated multi-step sequence of polymer supported reagents. J Chem Soc Perkin Trans 1 1251— 1252... 

The solid-phase synthesis of a-amino acids via alkaloid-catalyzed alkylation has been investigated by the O Donnell group [64, 65]. The solid-phase based synthetic approach is particularly useful for rapid preparation of a-amino acids for combinatorial application. The concept of this solid-phase synthetic approach, which comprises three key steps, is shown in Scheme 3.22 (for formation of (R) enantiomers). First, solid-phase bound glycine, 51, is converted into its benzophenone imine de-... 

MATHEY Phosphorus-Carbon Heterocyclic Chemistry The Rise of a New Domain McKILLOP Advanced Problems in Organic Reaction Mechanisms OBRECHT Solid Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries OSBORN Best Synthetic Methods - Carbohydrates PELLETIER Alkaloids Chemical and Biological Perspectives SESSLER WEGHORN Expanded Contracted and Isomeric Porphyrins WONG WHITESIDES Enzymes in Synthetic Organic Chemistry... 

Bonnet and Ganesan [12] developed a new route toward the solid-phase synthesis of tetrahydro-P-carboline hydantoins, which appear in a diverse array of biologically active alkaloids. Due to the presence of tetrahydro-P-carbolines and diketo-piperazine ring skeletons in several bioactive natural products, these two scaffolds became attractive targets for developing a combinatorial chemistry program. 

Combinatorial biosynthesis, that is, the combination of metabolic pathways in different organisms on a genetic level allowing the use of precursors of the host cells is another promising strategy for the synthesis and industrial production of important classes of natural products, including alkaloids (vinblastine, vincristine), terpenoids (artemisinin, pacUtaxel), and flavonoids [59],... 

Aberle, N.S. et ah. Parallel modification of tropane alkaloids, Tetrahedron Lett., 42, 1975, 2001. Clough, J. et ah. Combinatorial modification of natural products synthesis and in vitro analysis of derivatives of thiazole peptide antibiotic GE2270 A A-ring modifications, Bioorg. Med. Chem. Lett., 13, 3409, 2003. 

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