Biomedical subjects

Henner Knust

Publications and source records attributed to Henner Knust.

3 recordsLinked to original sources

PubMed2004

Synthesis of antimicrofilament marine macrolides: synthesis and configurational assignment of a C5-C16 degradation fragment of reidispongiolide A.

Reidispongiolide A is a representative member of the sphinxolide/reidispongiolide group of cytotoxic 26-membered macrolides of marine origin. By interacting with actin in the cell cytoskeleton, the reidispongiolides and sphinxolides are potent microfilament destabilizing agents that represent a promising mechanism of action for developing novel anticancer drugs. An aldol-based synthesis of a library of diastereomers of C(8)-C(16) and C(5)-C(16) fragments and detailed NMR comparison with a reported degradation fragment enabled a configurational assignment for a major part of the reidispongiolide macrocyclic core, thus setting a solid foundation for ongoing synthetic efforts.

Actin Cytoskeleton↗

PubMed2003

Toward the synthesis of reidispongiolide a: stereocontrolled synthesis of the C17-C22 and C23-C35 degradation fragments.

[structure: see text] By relying on the asymmetric aldol reactions of chiral ketones, a highly stereocontrolled synthesis of each of the C(17)-C(22) and C(23)-C(35) degradation fragments of reidispongiolide A has been achieved. This permits a configurational assignment of the complete C(17)-C(36) region of this antimitotic macrolide, along with providing advanced intermediates for a projected total synthesis.

Animals↗

PubMed2002

A case study in conformation design: learning by doing.

Efforts are described to design simple, fully flexible but conformationally preorganised omega-hydroxy-nonanoic acids that could serve as the conformation controlling unit in analogues of the potent protein-kinase C activator aplysiatoxin. Such analogues are macrodilactones incorporating the designed omega-hydroxy-nonanoic acid and 3,4-dihydroxy-pentanoic acid, which contains the pharmacophoric groups. The design process (replacement of CH(2) groups by an oxygen atom, annelation of a six-membered ring and placement of alkyl substituents) of the omega-hydroxy-nonanoic acids was monitored by force-field calculations. In the end of this process simple analogues of aplysiatoxin are proposed in which the proper disposition of the pharmacophoric groups is secured by a conformationally flexible but preorganised template structure as part of the macrodilactone ring.

Drug Design↗