Natural Product Synthesis
Natural Product Synthesis Publications Gallery
Relay Cross Metathesis for the Iterative Construction of Terpenoids and Synthesis of a Diterpene Benzoate Macrolide of Biogenetic Relevance to the
Total Syntheses of 12-Epoxyobtusallene IV, 12-Epoxyobtusallene II, Obtusallene X, Marilzabicycloallene C, and Marilzabicycloallene D
Proof-of-Principle Direct Double Cyclisation of a Linear C-15-Precursor to a Dibrominated Bicyclic Medium-Ring Ether Relevant to Laurencia Species
Epoxidation of Bromoallenes Connects Red Algae Metabolites by an Intersecting Bromoallene Oxide - Favorskii Manifold
A Unifying Stereochemical Analysis for the Formation of Halogenated C-15-Acetogenin Medium-Ring Ethers From Laurencia Species
Total Synthesis of the Marine Metabolite (+/-)-Polysiphenol via Highly Regioselective Intramolecular Oxidative Coupling
Intramolecular Bromonium Ion Assisted Epoxide Ring-Opening: Capture of the Oxonium Ion with an Added External Nucleophile
Bromonium Ion Induced Transannular Oxonium Ion Formation-Fragmentation in Model Obtusallene Systems and Structural Reassignment of Obtusallenes V-VII
Structural Reassignment of Obtusallenes V, VI, and VII by GIAO-Based Density Functional Prediction
The marine red algae of Laurencia species produce a dazzling array of halogenated natural products using halide from seawater. In 2006 we proposed a novel biogenesis for the Obtusallene family of natural products via electrophilic bromination,1 and followed this up shortly thereafter with a biosynthetically inspired synthesis of the tetrahydrofuran core of obtusallenes II and IV.2 The biogenesis suggested that some structural reassignments of the family were required, which were consistent with subsequent GIAO-based functional predictions.3 Subsequent bromonium ion induced transannular oxonium ion formation-fragementations in model obtusallenes led to the structural reassignment of obtusallenes V-VII.4 In 2016, this work culminated in the total synthesis of 12-epoxyobtusallene IV, 12-epoxyobtusallene II, obtusallene X, marilzabicycloallene C and marilzabicycloallene D.5 Notable outcomes from this project include defining the stereochemical course of bromoetherifcation of enynes,6 the prediction of the existence of the marilzabicycloallenes prior to their discovery, and the use of halogen-induced isotopic 13C NMR shifts for the identification of halogen bearing carbons.4 Further, we have also shown that epoxidation of bromoallenes connects red algae metabolites by an intersecting bromoallene-Favorskii manifold,7 which led to the the first stable and isolable bromoallene oxide.8 Notably, the latter paper reports the first X-ray crystal structure of any allene oxide.
In a related project we have reported a unifying stereochemical analysis for the halogenated medium ring ethers from Laurencia and experimental corroboration with a model epoxide,9 building on methodology based on intramolecular bromonium ion assisted epoxide ring-opening,10 and have reported a proof-of-principle direct double cyclisation of a linear C15-precursor to a dibrominated bicyclic medium ring ether relevant to Laurencia species.11
We have targeted other halogenated natural products from marine sources, and have reported a three step asymmetric hexafunctionalisation of myrcene as an approach to halomon,12 the first total synthesis of polysiphenol by highly regioselective intramolecular oxidative coupling,13 and the use of an iterative relay cross metathesis method for the synthesis of a diterpene-benzoate macrolide of biogenetic relevance to the bromophycolides.14
Work in the group continues in the area.
References:  Braddock, D. C. Org. Lett. 2006, 8, 6055-6058.  Bradock, D. C.; Bhuva, R.; Perez-Fuertes, Y.; Roberts, C. A.; Sheppard, R. N.; Solanki, S.; Stokes, E. S. E.; White, A. Org. Lett. 2007, 9, 445-448.  Braddock, D. C.; Rzepa, H. S. J. Nat. Prod. 2008, 71, 728-6730.  Braddock, D. C.; Millan, D. S.; Perez-Fuertes, Y.; Pouwer, R.; Sheppard, R. N.; Solanki, S.; White, A. J. P. J. Org. Chem. 2009, 74, 1835-1841 (Featured Article).  Clarke, J.; Bonney, K. J.; Yaqoob, M.; Solanki, Rzepa, H. S.; White, A. J. P.; Millan, D. S.; Braddock D. C. J. Org. Chem. 2016, 81, 9529-9552 (Featured Article).  Braddock, D. C.; Bhuva, R.; Perez-Fuertes, Y.; Pouwer, R.; Roberts, C. A.; Ruggiero, A.; Stokes, E. S. E.; White, A. J. P. Chem. Commun. 2008, 1419-1421. Braddock, D. C.; Clarke, J.; Rzepa, H. S. Chem. Commun. 2013, 49, 11176-11178.  Braddock, D. C.; Mahtey, A. Rzepa, H. S.; Chem. Commun. 2016, 52, 11219-11222.  Bonney, K. J.; Braddock, D. C.; J. Org. Chem. 2012, 77, 9574-9584.  Bonney, K. J.; Braddock, D. C.; White, A. J. P.; Yaqoob, M. J. Org. Chem. 2011, 76, 97-104.  Braddock, D. C.; Sbircea, D.-T. Chem. Commun. 2014, 50, 12691-12693.  Braddock, D. C.; Gao, A. X.; White, A. J. P.; Whyte, M. Chem. Commun. 2014, 50, 13725-12728.  Barrett, T. N.; Braddock, D. C.; Monta, A.; Webb, M. R.; White, A. J. P. J. Nat. Prod. 2011, 74, 1980-1984.  Bahou. K. A.; Braddock, D. C.; Meyer, A. G.; Savage, G. P. Org. Lett. 2020, 22, 3176-3179.