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The key building blocks required for the total synthesis of the originally proposed structure of azaspiracid were coupled with a potent marine-derived neurotoxin, and the products elaborated to the targeted compounds and their C-20 epimers. Neither of the final products matched the natural substances by thin layer chromatography or (super 1)H nuclear magnetic resonance spectroscopic analysis, suggesting one or more errors in the originally proposed structure for this biotoxin.

The second total synthesis of diazonamide A through a sequence entirely distinct from that employed in the first campaign, one whose success required the development of several special strategies and tactics is detailed. Complete studies regarding the chemical biology of diazonamide A and its structural congeners is disclosed, and the scope of the protocol for Robinson-Gabriel cyclodehydration using pyridine-buffered POCl3 is described.

The first successful total synthesis of diazonamide A is presented. The study not only verified its proper connectivities and established the stereochemistry of its previously unassignable C-37 chiral center, but also was attended by the development of several new synthetic strategies and tactics.

Total synthesis of englerin A, reported as sesquiterpenoid that exhibit potent and selective growth inhibition against renal cancer cell lines is presented. The successful synthesis method featured a [5 + 2] cycloaddition reaction to cast the seven-membered oxabicyclic key intermediate in both racemic and optically active forms.

The total synthesis and biological estimation of the resveratrol-derived natural products hopeanol and hopeahainol A in their racemic and antipodal forms are described. Biological evaluation of the synthesized compounds confirmed the reported acetylcholinesterase inhibitory activity of hopeahainol A but not the reported cytotoxic potencies of hopeanol.

Total syntheses of the highly selective antiproliferative natural products cortistatins A and J in their naturally occurring enantiomeric forms are described. The developed synthetic technologies could also be applied for the construction of several analogues of the cortistatins which were biologically evaluated and compared to the natural products with regards to their antiproliferative activities against a variety of cancer cells.

New synthetic methods are described for constructing novel heterocycles and tryptamines. The application of the new synthetic technologies to the preparation of regioisomeric spirocycles and tryptamines, Corey's aspidophytine tryptamine, and efavirenz are discussed.

An expedient and asymmetric synthetic route is disclosed to enone that has constituted a formal total synthesis of platencin. The described chemistry has offered an expedient catalytic asymmetric route to platencin and has provided an opportunity for rapid construction of analogues of this new antibiotic for biological and pharmacological studies.

Molecular design and chemical synthesis of many palmerolide A analogues have allowed the first structure activity relationships (SARs) of the newly discovered marine antitumor agent. The studies have helped in the design and synthesis of much more potent and selective palmerolide A analogues as biological tools and drug candidates.

The total syntheses of five palmerolide A stereoisomers and the revised [ent-(19-epi-20-epi-1) structures are described. The Homer-Wadsworth-Emmons olefination and the Yamaguchi lactonization are examined and are successful as a means to construct the palmerolide macrocycle.

The structural elucidation and total synthesis of azaspiracid-1, a neurotoxin isolated from mussels, are reported. Along with the total synthesis of azaspiracid-1, the syntheses of its C1-C20 epimer and of several truncated analogues for biological investigations are described.

Herein we report a novel synthetic entry to the legendary quinuclidine natural products quinine and quinidine. The developed strategy is based on the use of a symmetrical and nonstereogenic precursor to access quinine and quinidine through a "local‐desymmetrization" approach, in stark contrast conceptually to the preparation of stereodefined disubstituted piperidines (or their acyclic precursors) as featured in all past syntheses. The developed strategy also provided quinine and quinidine derivatives that could not be readily obtained through previous total syntheses or by modification of the naturally occurring substances. Seeing old friends in a new light: A divergent synthesis of quinine and quinidine (see structures) was designed on the basis of a symmetrical and nonstereogenic intermediate, conceptually different from the stereodefined piperidine precursors used in past syntheses. Complementary late‐stage local‐desymmetrization reactions were developed to access the two targets. The strategy also enabled the synthesis of novel quinine and quinidine derivatives. [ABSTRACT FROM AUTHOR]

Abstract: The field of organic synthesis is facing an exciting yet challenging time in its own history, and in the history of science and humanity. In this essay, personal perspectives in response to the five questions posed by the Editors of this Special Issue covering the history, contribution, perception, predictability, and future of organic synthesis, are presented. Through this collection of historical facts, personal viewpoints, encounters, and speculations, the scientific community and beyond may rejuvenate an appreciation for organic synthesis as both a powerful central science and an indispensable enabling technology, and collectively strive towards the next bright chapter in the human history. [ABSTRACT FROM AUTHOR]