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. 2009;48(1):104-9.
doi: 10.1002/anie.200804486.

Synthesis of natural-product-like molecules with over eighty distinct scaffolds

Daniel Morton  1 , Stuart Leach, Christopher Cordier, Stuart Warriner, Adam Nelson
Affiliations

Synthesis of natural-product-like molecules with over eighty distinct scaffolds

Daniel Morton et al. Angew Chem Int Ed Engl. 2009.
No abstract available

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Figures

Scheme 1
Scheme 1
Outline of our approach to the combinatorial variation of the scaffolds of small molecules. The labels in parentheses define the substituents: Ac=acetyl; Sil=diisopropylsilyl; All=allyl.
Scheme 2
Scheme 2
Structures of the building blocks used in our diversity-oriented approach. Enantiomeric structures are distinguished thus: 9 and 9′.
Scheme 3
Scheme 3
Selected examples of metathesis cascades leading to skeletally diverse products. Methods: Attachment of 21–26: 1) building block (4 equiv), DEAD (4 equiv), PPh3 (4 equiv), THF, 0°C, 1 h; 2) F-SPE. Attachment of 27: 1) building block (4 equiv), DEAD (4 equiv), PPh3 (4 equiv), THF, 0°C → reflux; 2) F-SPE. Silaketal formation: 1) building block (5.5 equiv), NBS (5 equiv), CH2Cl2, 0°C → RT, 15 min; 2) inverse addition of substrate (1 equiv, 0.2m), DMAP (50 mol%), Et3N (15 equiv), 0°C → RT; 3) F-SPE. Attachment of 28–30: 1) building block (2 equiv), EDC (2 equiv), DMAP (10 mol%), CH2Cl2, RT; 2) F-SPE. G-I: 1) catalyst G I, CH2Cl2, 45°C; 2) Et3N (86 equiv), P(CH2OH)3 (86 equiv), then silica, then filter through Celite; 3) F-SPE; 4) HF⋅pyridine, THF, then Me3SiOMe. HG-II: 1) catalyst HG II, CH2Cl2, 45°C; 2) Et3N (86 equiv), P(CH2OH)3 (86 equiv), then silica, then filter through Celite; 3) F-SPE. f-HG-II: 1) catalyst f-HG II, CH2Cl2, 45°C; 2) F-SPE. DEAD=diethyl azodicarboxylate; NBS=N-bromosuccinimide; DMAP=4-dimethylaminopyridine; EDC=N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide.
Scheme 4
Scheme 4
Some catalysts for metathesis reactions.
Scheme 5
Scheme 5
Fate of some metathesis cascade reactions.
Figure 1
Figure 1
Hierarchical classification which illustrates the relationship between parental scaffolds (blue), daughter scaffolds (red), and molecular scaffolds (black).
See this image and copyright information in PMC

Comment in

  • Synthesis of unprecedented scaffold diversity.
    Galloway WR, Diáz-Gavilán M, Isidro-Llobet A, Spring DR. Galloway WR, et al. Angew Chem Int Ed Engl. 2009;48(7):1194-6. doi: 10.1002/anie.200805452. Angew Chem Int Ed Engl. 2009. PMID: 19137520

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