Stereo-Controlled Synthesis of Vicinal Tertiary Carbinols: Application in the Synthesis of a Diol Substructure of Zaragozic Acid, Pactamycin and Ryanodol.

A novel and flexible approach for the stereo-controlled synthesis of vicinal tertiary carbinols is reported. The developed strategy featured a highly diastereoselective singlet-oxygen (O2 1 ) [4+2] cycloaddition of rationally designed cyclohexadienones (derived from oxidative dearomatization of the corresponding carboxylic-acid appended phenol precursors), followed by programmed "O-O" and "C-C" bond cleavage. In doing so, a highly functionalized and versatile intermediate was identified and prepared in synthetically useful quantity as a plausible precursor to access a variety of designed and naturally occurring vicinal tertiary carbinol containing compounds. Most notably, the developed strategy was successfully applied in the stereo-controlled synthesis of advanced core structures of zaragozic acid, pactamycin and ryanodol.

Chemistry and biology of diazonamide A: second total synthesis and biological investigations.

As an especially unique target for chemical synthesis, diazonamide A has the potential to be constructed through a plethora of synthetic routes, each attended by different challenges and opportunities for discovery. In this article, we detail our second total synthesis of diazonamide A through a sequence entirely distinct from that employed in our first campaign, one whose success required the development of several special strategies and tactics. We also disclose our complete studies regarding the chemical biology of diazonamide A and its structural congeners, and more fully delineate the scope of our protocol for Robinson-Gabriel cyclodehydration using pyridine-buffered POCl(3).

Studies toward diazonamide A: development of a hetero-pinacol macrocyclization cascade for the construction of the bis-macrocyclic framework of the originally proposed structure.

In this article, we describe further studies toward the originally proposed structure of diazonamide A (1). After confronting a number of failures in synthesizing the heterocyclic core of that structure, success was finally realized through the development of a novel hetero-pinacol-based macrocyclization cascade sequence. Subsequent elaboration led to an advanced compound bearing both of the 12-membered rings of the target molecule. In addition, preliminary biological studies with intermediates and simplified analogues obtained via the developed sequences are also described.

Asymmetric Weitz-Scheffer epoxidation of isoflavones with hydroperoxides mediated by optically active phase-transfer catalysts.

The asymmetric Weitz-Scheffer epoxidation of the isoflavones 3, mediated by the cinchonine- and cinchonidine-derived phase-transfer catalysts (PTCs) 1, affords the enantiomerically enriched isoflavone epoxides 4 with ee values of up to 98% in nearly quantitative yields. With the appropriately configured PTC 1, both enantiomers of the isoflavone epoxides may be obtained by using the commercially available cumyl hydroperoxide 2b as oxidant. Methylation of the hydroxy functionality in the most effective PTC (1b) reduces significantly the enantioselectivity of the isoflavone epoxidation as illustrated for the substrate 3c. This fact indicates the pivotal role of the hydroxy group for enantioselective control, which is rationalized in terms of a hydrogen-bonded aggregate between the ether-oxygen atom of isoflavone 3 and the phase-transfer catalyst 1. The present attractive and convenient method should be useful for the preparation of optically active epoxides of the biologically relevant isoflavone structure.