Synthesis and structural characterization of cross-linked histidine-phenol Cu(ii) complexes as cytochrome c oxidase active site models

Tridentate cross-linked histidine-phenol Cu(ii) ether and ester complexes, chemical analogs of the active site of several heme-copper oxidases, have been synthesized and crystallized.     

Welwistatin support studies: expansion and limitation of aryllead(IV) coupling reactions

Recent support studies on the total synthesis of the welwistatin system are described. The target step involves lead-mediated arylation of sterically demanding aryl groups and carbon acid coupling partners in order to establish the highly congested tetracyclic core structure. Type 7 beta-ketoesters and beta-ketonitriles were successfully arylated with a variety of ortho- and meta-substituted aryllead compounds generated by a halogen-boron-lead exchange sequence. The enolates of compounds 15, 19, and 25, each bearing all-carbon quaternary centers adjacent to the arylation site, failed to couple.     

tert-Buyldiphenylsilylethyl ("TBDPSE"): a practical protecting group for phenols

[reaction: see text] A new protection group for phenols, the 2-(tert-butyldiphenylsilyl)ethyl (TBDPSE) group, has been prepared and investigated. Protection of a variety of substituted phenols proceeds in good to excellent yield. The group is stable to mild acid, base, hydrogenolysis conditions, and lithium/halogen exchange on the protected phenol. Removal is achieved with strong acid or standard fluoride treatment.     

Progress toward a peptidomimetic of laminin-derived pentapeptide YIGSR: synthesis of the unique tricyclic core structure

The peptide sequence YIGSR, a segment of the basement membrane matrix glycoprotein laminin, has been identified as a key component in tumor cell invasion. Guided by extensive NMR work and de novo design algorithms, a nonpeptide mimetic of this pentapeptide was identified as a lead candidate for synthesis. The target displays the key amino acid side chains from a novel tricyclic scaffold. The first synthesis of this unique scaffold is completed in 11 steps and 7% overall yield.     

Structural characterization of an enantiomerically pure amino acid imidazolide and direct formation of the beta-lactam nucleus from an alpha-amino acid

Decomposition of a diazo beta-ketoamide derived from N-trityl serine imidazolide and N-protected acetanilides provides, instead of the expected 3-acyloxindole product, an enantiomerically pure (EP) beta-lactam. The amino acid stereocenter is incorporated, the second chiral center is induced, and trityl protection of the beta-lactam ring is realized for the first time. The desired 3-acyloxindole is obtained from oxindole and Tr-Ser(OBn)-imidazole, the X-ray of which provides the first structural determination of an EP amino acid imidazolide.     

Diazonamide support studies: stereoselective formation of the C10 chiral center in both the CDEFG and AEFG fragments

The synthesis of both the AEFG macrolactam and the CDEFG bis-indole/tyrosine units found in the marine natural product diazonamide A is presented. Key to the success of the synthesis is the highly stereoselective direct C-arylation of an oxindole by an aryllead(IV) reagent derived from tyrosine.