Inspirations from nature. New reactions, new therapeutic leads, and new drug delivery systems

Abstract

Studies in our laboratory focus on problems in chemistry (new reactions and synthesis), biology (novel modes of action), and medicine (new therapeutic leads and drug delivery systems). These interconnected and often synergistic activities are inspired by an interest in novel structures, frequently from nature, that possess unique modes of action and significant clinical potential. Described herein are some examples of recent work from our laboratory that have led to new transition metal-catalyzed reactions, a new and remarkably potent therapeutic lead, and new drug delivery systems that are in clinical trials.

Protein kinase C, an elusive therapeutic target?

“…Preferred protection of PKC from down-regulation by the strong ligand, phorbol ester 84 led to a function-oriented synthetic approach to the design of selective PKC-binding bryostatin analogues 85 . These molecules show isozyme selectivity in binding the C1 domain 86 of various PKCs and may represent a novel class of PKC regulators 87,88 .…”

Total Synthesis and Structural Elucidation of Natural Products: (‐)‐Delactonmycin, (+)‐Plumerinine, and (‐)‐Parvistemoamide

“…Rev gene is essential for HIV replication, and its protein must be translocated from nucleus to cytoplasm to exert its function and thus could be a potential target for HIV-1 therapy. Among the compounds isolated were some that had been previously reported in the literature, such as leptomycin A (1), leptomycin B (2) [10], kazusamycin A (3), and kazusamycin B (4) [11] and a novel polyketide named delactonmycin, which had its planar structure proposed based on spectroscopic analysis (Fig. 1).…”

“…Since Emil Fischer's legendary work on the chemistry of biomolecules such as carbohydrates, peptides, and purines [1] up to its current level of sophisticated artistic endeavor [2], synthetic organic chemistry has played a definitive role not only in structural determination of natural and non-natural compounds, but has served as the testing ground to invent and test the scope and limitations of synthetic methodologies [3,4]. Over the years, our interest in synthetic organic chemistry was initially sustained by the unique biological activities of natural compounds such as pheromones [5], polyketides [6], and alkaloids [7] of established chemical structure and steadily evolved to the structural confirmation of the molecular architecture as we stumbled into some examples of structure misassignment in the literature and became interested in applying our knowledge of stereochemical control to the determination of the configuration of some natural products.…”

Efficient Domino Strategy for the Synthesis of Substituted Bipyrazole Derivatives

“…Then, the multicomponent domino reaction for the synthesis of biologically and pharmacologically important active molecules has become useful tools because of their efficiency and green chemistry characteristic . These reactions avoid time‐consuming and costly processes for separation and purification of precursors and tedious steps of protection procedures . Therefore, the development of new domino reactions for diversity of active molecules is a continuing challenge for modern organic synthesis.…”