Studies towards bioinspired synthesis of homodimericin A and total synthesis of dimeric epoxyquinoids and its biologically related monomeric natural products

Abstract

1. Homodimericin A was proposed to be derived from the two-hydroquinone precursors through a series of intriguing transformations. The monomeric precursor could then undergo homodimerization through a Baldwin forbidden double Michael cyclization. which undergo an intramolecular Diels-Alder reaction to give the pentacyclic framework. Finally, the pentacyclic framework could rearranged to homodimericin A through an intramolecular vinylogous aldol reaction. Herein, we describe the toward bioinspired synthesis of homodimericin A. Keywords: homodimericin A, dimerization, intramolecular Diels–Alder reaction, cascade reaction

2. We describe the total synthesis of epoxyquinoid natural products (+)-pestalofone A and (+)-iso-A82775C. The synthesis of (+)-16-oxo-iso-A82775C, the putative biosynthetic precursor of pestalofone C yet to be isolated, is also presented. The allene moiety present in (+)-iso-A82775C and (+)-16-oxo-iso-A82775C was constructed from the ketodiene-yne group via a biosynthetically relevant sequence involving a conjugate reduction and a base-catalyzed tautomerization. Attempted Diels–Alder reaction-based dimerizations of (+)-16-oxo-iso-A82775C and (+)-iso-A82775C towards pestalofones B and C are also described.

Keywords: iso-A82775C, pestalofone A, ketodiene-yne isomerization

3. The first total synthesis of (+)-dimericbiscognienyne A is described. Key to the successful access to (+)-dimericbiscognienyne A was a biosynthetically inspired Diels−Alder reaction between two differential epoxyquinoid monomers and the subsequent intramolecular hemiacetal formation. The selective formation of the natural product among other possible diastereomers during the late-stage [4+2] cycloaddition reaction was investigated by DFT calculations and experimental control studies.

Keywords: dimericbiscognineyne A, intermolecular Diels–Alder reaction, biomimetic synthesis