Efficient Synthesis of Cryptophycin-52 and Novel para-Alkoxymethyl Unit A Analogues
| Autor: | Stefan Eissler, Markus Nahrwold, Norbert Sewald, Tobias Bogner |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Lactams
Stereochemistry Diol asymmetric synthesis Antineoplastic Agents Metathesis Hydroxylation Catalysis antitumor agents Stereocenter Cryptophycin 52 chemistry.chemical_compound Lactones depsipeptides Cell Line Tumor Humans total synthesis natural Chemistry Organic Chemistry Enantioselective synthesis Total synthesis Stereoisomerism General Chemistry Combinatorial chemistry products Dihydroxylation Drug Resistance Neoplasm Cryptophycins |
| DOI: | 10.1002/chem.200901750 |
| Popis: | Cryptophycins are a family of highly cytotoxic, cyclic depsipeptides. They display antitumour activity that is largely maintained for multidrug-resistant tumour cells. Cryptophycins are composed of four building blocks (units A-D) that correspond to the respective amino and hydroxy acids. A new synthetic route to unit A allows the selective generation of all four stereogenic centres in a short, efficient and reliable synthesis and contributes to an easier and faster synthesis of cryptophycins. The first two stereogenic centres are introduced by a catalytic asymmetric dihydroxylation, whereas the remaining two stereogenic centres are introduced with substrate control of diastereoselectivity. The stereogenic diol function also serves as the epoxide precursor. The approach was used to synthesise the native unit A building block as well as three para-alkoxymethyl analogues from which cryptophycin-52 and three analogous cryptophycins were prepared. Macro-cyclisation of the seco-depsipeptides was based on ring-closing metathesis. |
| Databáze: | OpenAIRE |
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