Passive and catalytic antibodies and drug delivery

Antibodies are one of the most promising components of the biotechnology repertoire for the purpose of drug delivery. On the one hand, they are proven agents for cell-selective delivery of highly toxic agents in a small but expanding number of cases. This technology calls for the covalent attachment of the cytotoxin to a tumor-specific antibody by a linkage that is reversible under appropriate conditions (antibody conjugate therapy, ACT —"passive delivery”). On the other hand, the linker cleavage can be accomplished by a protein catalyst attached to the tumor-specific antibody ("catalytic delivery”). Where the catalyst is an enzyme, this approach is known as antibody-directed enzyme prodrug therapy (ADEPT). Where the transformation is brought about by a catalytic antibody, it has been termed antibody-directed abzyme prodrug therapy (ADAPT). These approaches will be illustrated with emphasis on how their demand for new biotechnology is being realized by structure-based protein engineerin

Simple and Efficient Preparation of Dihydropyrans and Spiroketals Using the Intramolecular Silyl Modified Sakurai (isms) Reaction

Substituted tetrahydropyrans, spiroethers and spiroketals can be prepared in a single step using the ISMS reaction between the bis-silylated reagent 7b and aldehydes (acetals), ketones (ketals) and ortholactones respectively. This simple methodology was applied to the rapid synthesis of a pheromone containing a [4,5]-spiroketal unit

Tandem ene-reaction/intramolecular Sakurai Cyclisation (IMSC): A novel access to polysubstituted tetrahydropyrans and gamma-butyrolactones using a unique allylation strategy

The ene-reaction between a variety of aldehydes and allylsilane 22 generates highly functionalised homoallylic alcohols 23. These adducts undergo a subsequent Intramolecular Sakurai Cyclisation (IMSC), affording in good yields polysubstituted tetrahydropyran derivatives. Furthermore, oxidative desilylation of 23 provides an efficient, connective access to a range of gamma-butyrolactones and alpha-methylene-gamma-butyrolactones

Multicomponent cyclisations. Efficient methodologies for the preparation of complex natural products

The Silyl-Modified Sakurai (SMS) reaction and its intramolecular variant, the ISMS cyclisation, are powerful methodologies that can provide easy access to a range of important subunits present in a variety of complex biologically active natural products

Passive and catalytic antibodies and drug delivery

Antibodies are one of the most promising components of the biotechnology repertoire for the purpose of drug delivery. On the one hand, they are proven agents for cell-selective delivery of highly toxic agents in a small but expanding number of cases. This technology calls for the covalent attachment of the cytotoxin to a tumor-specific antibody by a linkage that is reversible under appropriate conditions (antibody conjugate therapy, ACT —“passive delivery”). On the other hand, the linker cleavage can be accomplished by a protein catalyst attached to the tumor-specific antibody (“catalytic delivery”). Where the catalyst is an enzyme, this approach is known as antibody-directed enzyme prodrug therapy (ADEPT). Where the transformation is brought about by a catalytic antibody, it has been termed antibody-directed abzyme prodrug therapy (ADAPT). These approaches will be illustrated with emphasis on how their demand for new biotechnology is being realized by structure-based protein engineering