Total Syntheses of (+)- and (−)-Tetrapetalones A and C

Abstract

Described herein are syntheses of the naturally occurring polyketides (-)-tetrapetalones A and C and their respective enantiomers. The employed strategy involves initial assembly of a masked N-aryl tetramic acid which is advanced via a highly selective conjugate addition/intramolecular Friedel-Crafts acylation sequence to deliver a key azepine intermediate. Application of recently developed C-H activation chemistry and subsequent Heck cyclization delivers the aglycone framework in an overall 12 steps. Resolution of the aglycone via stereospecific glycosylation with an enantiopure glycosyl donor followed by separation of the derived diastereomers enables further advancement to either (+)- or (-)-tetrapetalones A and C.

Intramolecular Heck Reaction in Total Synthesis of Natural Products: An Update

“…(+)-Tetrapetalones A (193) and C (194) act as serine-βlactamase inhibitor as well as lipoxygenase inhibitor. In 2017 Wood et al [57] reported the total synthesis of (+)-tetrapetalones A (193) and C (194) where precursors 191 a/b were exposed to Heck reaction conditions under heating (24 h) or microwave (8 h) to furnish advance intermediates 192 a/b in good yield (Scheme 20). In 2016, Wong et al [58] also have adopted Pdcatalyzed intramolecular Heck reaction to prepare compound 196 from precursor 195 which was the essential intermediate to complete the total synthesis of bioactive plakortin polyketide (�)-gracilioether F (197) (Scheme 20).…”

“…(+)‐Tetrapetalones A ( 193 ) and C ( 194 ) act as serine‐β‐lactamase inhibitor as well as lipoxygenase inhibitor. In 2017 Wood et al [57] . reported the total synthesis of (+)‐tetrapetalones A ( 193 ) and C ( 194 ) where precursors 191 a/b were exposed to Heck reaction conditions under heating (24 h) or microwave (8 h) to furnish advance intermediates 192 a/b in good yield (Scheme 20).…”

Molecular Complexity from Aromatics: Recent Advances in the Chemistry of paraQuinol and Masked para‐Quinone Monoketal

“…Here, glycosylation also gave some amount of another diastereomer 416 , which was utilized for the synthesis of another isomer of the natural product (−)‐tetrapetalone A in a few steps (Scheme 48). [112] …”

“…Here, glycosylation also gave some amount of another diastereomer 416, which was utilized for the synthesis of another isomer of the natural product (À )-tetrapetalone A in a few steps (Scheme 48). [112] Zheng et al reported the total synthesis of caesalpinnone A, starting from resorcinol. Key features of the strategy were organocatalyzed [4 + 2] cycloaddition, trans-selective nucleophilic substitution, oxa-Michael addition, and photo-Fries rearrangement reactions.…”

Total Synthesis and Antibacterial Activity Evaluation of Griseofamine A and 16-epi-Griseofamine A

“…Tetramic acid (pyrrolidine-2,4-dione) units are common in the secondary metabolites of microorganisms and frequently have an acyl substituent at position 3 to afford 3-acyl tetramic acid. Natural products or bioactive molecules containing the 3-acyl tetramic acid motif exhibit a variety of biological activities, including antibacterial, antiviral, and anticancer activities. − Among these activities, antibacterial activity is of particular interest because 3-acyl tetramic acid was recently reported to play a crucial role in the quorum sensing of Gram-negative bacteria. − The isoprenyl group of griseofamine A is also an intriguing fragment, as this motif has been shown to improve the interactions between small molecules and proteins …”