An Assembly Concept for the Consecutive Introduction of Unsymmetrical Disulfide Bonds:  Synthesis of a Releasable Multidrug Conjugate of Folic Acid

We describe the development of methodology which allows for the introduction of a second disulfide bond into a molecular framework with a pre-existing disulfide linker system. Compounds which contain an S-9-fluorenylmethyl-protected thiol and an additional disulfide linkage are deprotected in situ a...

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Bibliographic Details
Published in:Journal of organic chemistry 2007-08, Vol.72 (16), p.5968-5972
Main Authors: Vlahov, Iontcho R, Santhapuram, Hari Krishna R, Wang, Yu, Kleindl, Paul J, You, Fei, Howard, Stephen J, Westrick, Elaine, Reddy, Joseph A, Leamon, Christopher P
Format: Article
Language:English
Subjects:
Carrier Proteins - chemistry
Chemistry
Chemistry, Organic - methods
Chemistry, Pharmaceutical - methods
Disulfides - chemistry
Drug Delivery Systems
Drug Design
Exact sciences and technology
Folic Acid - chemistry
Ligands
Models, Chemical
Organic chemistry
Peptides
Peptides - chemistry
Preparations and properties
Sulfhydryl Compounds
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Summary:We describe the development of methodology which allows for the introduction of a second disulfide bond into a molecular framework with a pre-existing disulfide linker system. Compounds which contain an S-9-fluorenylmethyl-protected thiol and an additional disulfide linkage are deprotected in situ and trapped with an activated thiophile. This methodology allowed for the synthesis of the first molecule possessing two different biologically active agents covalently attached to a folate receptor targeting ligand unit via two disulfide-based release systems.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo070411z