Synthesis of a reduced ring analog of didemnin B

Please use this identifier to cite or link to this item: http://ir.lib.ncu.edu.tw/handle/987654321/28419

Title:	Synthesis of a reduced ring analog of didemnin B
Authors:	Ramanjulu,JM;Ding,XB;Joullie,MM;Li,WR
Contributors:	中央大學
Keywords:	IMMUNOSUPPRESSIVE CYCLIC PEPTIDE;PHASE-II TRIAL;SODIUM TRIACETOXYBOROHYDRIDE;REDUCTIVE AMINATION;CARIBBEAN TUNICATE;DEPSIPEPTIDE;ALDEHYDES;INHIBITION;OXIDATION;INVITRO
Date:	1997
Issue Date:	2010-06-29 19:48:32 (UTC+8)
Publisher:	化學研究所
Abstract:	As part of investigations directed toward the determination of the essential/nonessential structural features for the bioactivities of didemnin B, we designed a reduced ring analog in which three moieties, namely the tyrosine side chain, the isostatine hydroxyl, and the side chain (L-lactyl-L-prolyl-N-Me-D-leucine), were in their presumed bioactive conformation. In designing the reduced ring analog, we eliminated the leucine-proline portion of the macrocycle core and replaced if with an n-butyl linker in order to elucidate its role. According to MM2 calculations (MacroModel molecular modeling), this analog was of lower energy than the natural product didemnin B, and both structures were superimposable. The synthetic strategy involved four disconnections. Macrocyclization was accomplished at the activated carboxylic acid of the alpha-(alpha-hydroxyisovaleryl)-propionyl unit (HIP) and the protected amine of the n-butyl linker using a modification of Schmidt's protocol. After selective deprotection of the hydroxyl and amino groups of the macrocycle, the peptide side chain was introduced using (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as the activating reagent.
Relation:	JOURNAL OF ORGANIC CHEMISTRY
Appears in Collections:	[Graduate Institute of Chemistry] journal & Dissertation

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