Rapid, high-yield, solid-phase synthesis of the antitumor antibiotic sansalvamide A using a side-chain-tethered phenylalanine building block.
A 10-step solid-phase synthesis of the cytotoxic depsipeptide sansalvamide A (1) has been accomplished in an overall yield of 67% with >95% purity employing polymer-bound phenylalanine building block 2. Both the N- and C-termini of 2 are extended followed by on-resin head-to-tail macrocyclization of the linear peptide in a high yield. This should be a general stategy for the synthesis of diverse libraries of cyclic peptides and depsipeptides that contain exclusively phenylalanine and other hydrophobic side chains.
Lee
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Y
Department of Chemistry, Northwestern University, Evanston, Illinois 60208-3113, USA.
Silverman
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RB
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D003500:Cyclization; D047630:Depsipeptides; D005670:Fusarium / Q000737:chemistry; D007202:Indicators and Reagents; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D010649:Phenylalanine / Q000737:chemistry*
D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D007202:Indicators and Reagents; D010456:Peptides, Cyclic; C119376:sansalvamide A; D010649:Phenylalanine