A stereoselective total synthesis of (−)-Renieramycin T (1t) from a key tetrahydroisoquinoline intermediate previously utilized in our formal total synthesis of Ecteinascidin 743 is described. The synthesis features a concise approach for construction of the pentacyclic framework using a Pictet–Spengler cyclization of bromo-substituted carbinolamine 17, which obviates the regioselectivity problem of the Pictet–Spengler cyclization. The results of cytotoxicity studies are also presented.

The formation of a series of analogs containing a pyridine moiety in place of the natural thiazole heterocycle, based on the potent, naturally occurring HDAC inhibitor Largazole has been accomplished. The synthetic strategy was designed modularly to access multiple inhibitors with different aryl functionalities containing both the natural depsipeptide and peptide isostere variant of the macrocycle. The cytotoxicity and biochemical activity of the library of HDAC inhibitors is described herein.

Eight examples of biosynthetic pathways wherein a natural enzyme has been identified and claimed to function as a catalyst for the [4 + 2] cycloaddition reaction, namely, Diels–Alderases, are briefly reviewed. These are discussed in the context of the mechanistic challenges associated with the technical difficulty of proving that the net formal [4 + 2] cycloaddition under study indeed proceeds through a synchronous mechanism and that the putative biosynthetic enzyme deploys the pericyclic transition state required for a Diels–Alder cycloaddition reaction.