Hybrids, Congeners, Mimics, and Constrained Variants Spanning 30 Years of Natural Products Chemistry: A Personal Retrospective

My 50-Plus Years of Academic Research Collaborations with Industry. A Retrospective

“…The saga of the aeruginosins continued in our collaboration with scientists at AstraZeneca with another felicitous discovery. A 2002 patent revealed yet a newer member of the aeruginosin family isolated from another aquatic source which we named chlorodysinosin A (20). A total synthesis confirmed the structure and stereochemistry of the 2S,3R-chloroleucine residue.…”

“…It is also an excellent forum to teach the art and science of synthesis to students and as a result, to invent new reactions. [12][13][14][15][16][17][18]20,21 I hope that natural product synthesis will continue to thrive as new biological targets are discovered in this exciting era of genomics and other "omics" by pharma and by academics to address unmet medical needs.…”

“…Over the years, the total synthesis of natural products has been a marquis area of research and a measure of creativity among peers. It is also an excellent forum to teach the art and science of synthesis to students and as a result, to invent new reactions. − ,, I hope that natural product synthesis will continue to thrive as new biological targets are discovered in this exciting era of genomics and other “omics” by pharma and by academics to address unmet medical needs.…”

“…Some of the medicinally relevant if not life-saving natural products have originated from academia and from the microbiology departments of pharmaceutical companies. Their biomedical relevance, and at times scarcity in quantity, has been a compelling incentive for total synthesis as a challenge as well as a forum to practice creativity and ingenuity while providing valuable training for students. , In many ways, as God’s gift to humankind and to the synthetic organic chemist, natural products are the enticers, the teasers, and the healers. − …”

Synthesis of Aza-Bridged Perhydroazulene Chimeras of Tropanes and Hederacine A

“…The interaction of synthetic small organic molecules with biological macromolecules such as enzymes, receptors, and nucleic acids has been the foundation of the arduous process of drug discovery in the pharmaceutical industry for decades. − Heterocyclic compounds have played a major role in the development of a large number of marketed drugs . In parallel, natural products have been a rich source of medicines for human illnesses dating back to centuries including in the archives of traditional medicines. , To the synthetic chemist, nature is the healer, the enticer, and the provider of an inexhaustible reservoir of fascinating molecules that have changed our world to the benefit of mankind. − Natural products have also inspired synthetic chemists to engage in total synthesis using enabling methodologies, thereby making available materials for biological testing especially of arduously accessible compounds. − Advances in structural biology and cocrystallographic techniques of small molecules with medicinally relevant enzymes have provided powerful tools to probe interactions at the molecular level leading to the so-called structure-based design of drugs . Knowledge of such interactions has instigated synthetic chemists to creatively conceive new structural entities resembling segments of the natural products as truncated or functionally more simplified analogues. − The synthesis of structural mimetics of bioactive natural products has been an active area of drug development for decades.…”