Total Syntheses of Highly Oxidized ent-Kaurenoids Pharicin A, Pharicinin B, 7-O-Acetylpseurata C, and Pseurata C: A [5+2] Cascade Approach.

The unprecedented oxidative dearomatization-induced [5+2] cycloaddition/pinacol-type 1,2-acyl migration cascade efficiently generates a quaternary carbon center and assembles the highly oxygenated bicyclo[3.2.1]octane framework of ent-kaurene diterpenoids. By incorporation of the subsequent retro-aldol/aldol process and singlet oxygen ene reaction, this concise and convergent approach has enabled the first asymmetric total syntheses of pharicin A, pharicinin B, 7-O-acetylpseurata C, and pseurata C.

[1]  Corinna S. Schindler,et al.  New avenues for the synthesis of ent-kaurene diterpenoids , 2015 .

[2]  Junjie Wang,et al.  Convergent Route to ent-Kaurane Diterpenoids: Total Synthesis of Lungshengenin D and 1α,6α-Diacetoxy-ent-kaura-9(11),16-dien-12,15-dione. , 2017, Journal of the American Chemical Society.

[3]  Sarah E Reisman,et al.  A concise total synthesis of (-)-maoecrystal Z. , 2011, Journal of the American Chemical Society.

[4]  Z. Gu,et al.  Total synthesis of maoecrystal V: early-stage C-H functionalization and lactone assembly by radical cyclization. , 2013, Journal of the American Chemical Society.

[5]  Eiichi Fujita,et al.  Terpenoids. Part XXVIII. Total synthesis of enmein , 1974 .

[6]  K. Nicolaou,et al.  A mild and selective method for the hydrolysis of esters with trimethyltin hydroxide. , 2005, Angewandte Chemie.

[7]  Armen Zakarian,et al.  Enantioselective Synthesis of (−)-Maoecrystal V by Enantiodetermining C–H Functionalization , 2014, Journal of the American Chemical Society.

[8]  L. Paquette,et al.  FIRST SYNTHESIS OF CYTOTOXIC 8,9-SECOKAURENE DITERPENOIDS. AN ENANTIOSELECTIVE ROUTE TO (-)-O-METHYLSHIKOCCIN AND (+)-O-METHYLEPOXYSHIKOCCIN , 1997 .

[9]  Dattatraya H. Dethe,et al.  Enantiospecific total syntheses of meroterpenoids (-)-F1839-I and (-)-corallidictyals B and D. , 2016, Organic & biomolecular chemistry.

[10]  R. D. Bach,et al.  Concerted 1,2-carbonyl migrations in organic synthesis. A practical synthesis of spiro cyclic 1,3-diketones , 1985 .

[11]  H. Ding,et al.  Total synthesis of diterpenoid steenkrotin A. , 2015, Angewandte Chemie.

[12]  C. Liao,et al.  Diastereoselective intramolecular Diels–Alder reactions of masked o-benzoquinones: a short entry to highly functionalized tricyclic [m.2.2.0] ring systems , 2001 .

[13]  A. Eschenmoser,et al.  Eine neuartige Fragmentierung cyclischer α, ß-ungesättigter Carbonylsysteme; Synthese von Exalton und rac-Muscon aus Cyclododecanon Vorläufige Mitteilung , 1967 .

[14]  B. Foxman,et al.  Total Syntheses of (±)-Isosteviol and (±)-Beyer-15-ene-3β,19-diol by Manganese(III)-Based Oxidative Quadruple Free-Radical Cyclization , 1998 .

[15]  R. J. Thomson,et al.  Enantioselective total synthesis of (-)-maoecrystal V. , 2014, Journal of the American Chemical Society.

[16]  T. Pettus,et al.  An oxidative dearomatization-induced [5 + 2] cascade enabling the syntheses of α-cedrene, α-pipitzol, and sec-cedrenol. , 2011, Journal of the American Chemical Society.

[17]  J. Stryker,et al.  [5 + 2] cycloaddition reactions in organic and natural product synthesis. , 2013, Chemical reviews.

[18]  Sarah E Reisman,et al.  A unified strategy to ent-kauranoid natural products: total syntheses of (-)-trichorabdal A and (-)-longikaurin E. , 2013, Journal of the American Chemical Society.

[19]  W. Adam,et al.  The Schenck Ene Reaction: Diastereoselective Oxyfunctionalization with Singlet Oxygen in Synthetic Applications†‡ , 1996 .

[20]  M. Tanabe,et al.  A novel fragmentation reaction of α,β-epoxyketones the synthesis of acetylenic ketones☆ , 1967 .

[21]  H. Wasserman,et al.  Singlet oxygen in organic synthesis , 1981 .

[22]  Xiaoguang Lei,et al.  Advanced in the Synthesis of Kaurane Diterpenoids , 2015 .

[23]  R. Church,et al.  Experiments directed toward the total synthesis of terpenes. VII. The synthesis of (+or-)-8-beta-carbomethoxy-13-oxopodocarpanone, a degradation product of phyllocladene. , 1966, The Journal of organic chemistry.

[24]  Li-Sheng Ding,et al.  ent-Kaurane diterpenoids from Isodon pharicus. , 2009, Journal of natural products.

[25]  R. J. Thomson,et al.  Total synthesis of the Isodon diterpene sculponeatin N. , 2014, Angewandte Chemie.

[26]  K. Mori,et al.  Diterpenoid total synthesis—II : An alternate route to methyl (±)-7-oxopodocarp-8-en-16-oate , 1966 .

[27]  Phil S Baran,et al.  Synthesis of ent-kaurane and beyerane diterpenoids by controlled fragmentations of overbred intermediates. , 2013, Angewandte Chemie.

[28]  S. Quideau,et al.  λ3-Iodane-mediated arenol dearomatization. Synthesis of five-membered ring-containing analogues of the aquayamycin ABC tricyclic unit and novel access to the apoptosis inducer menadione , 2005 .

[29]  Yaozu Chen,et al.  Diterpenoids from Rabdosia pseudo-irrorata , 1990 .

[30]  Ronan Batista,et al.  Occurrence, biological activities and synthesis of kaurane diterpenes and their glycosides. , 2007, Molecules.

[31]  E. Corey,et al.  Enantioselective Total Synthesis of the Potent Anti-HIV Agent Neotripterifordin. Reassignment of Stereochemistry at C(16) , 1997 .

[32]  Han-Dong Sun,et al.  Diterpenoids from Isodon species and their biological activities. , 2006, Natural product reports.

[33]  P. Dussault,et al.  Fragmentation of chloroperoxides: hypochlorite-mediated dehydration of hydroperoxyacetals to esters. , 2010, Tetrahedron letters.

[34]  Jing-Chun Han,et al.  Catalytic Enantioselective Total Synthesis of Hypocrolide A. , 2016, Organic letters.

[35]  Wei‐Lie Xiao,et al.  Diterpenoids from Isodon pharicus , 2009 .

[36]  R. Turner,et al.  The Total Synthesis of Phyllocladene1,2 , 1966 .

[37]  Phil S. Baran,et al.  11-Step Total Synthesis of (−)-Maoecrystal V , 2016, Journal of the American Chemical Society.

[38]  R. J. Thomson,et al.  The total synthesis of Isodon diterpenes. , 2014, Angewandte Chemie.

[39]  Y. Zeng,et al.  ExcisaninA, a diterpenoid compound purified from Isodon MacrocalyxinD, induces tumor cells apoptosis and suppresses tumor growth through inhibition of PKB/AKT kinase activity and blockade of its signal pathway , 2009, Molecular Cancer Therapeutics.

[40]  Guoqiang Chen,et al.  Pharicin A, a novel natural ent-kaurene diterpenoid, induces mitotic arrest and mitotic catastrophe of cancer cells by interfering with BubR1 function , 2010, Cell cycle.

[41]  Sha-Hua Huang,et al.  Constructive innovation of approaching bicyclo[3.2.1]octane in ent-kauranoids , 2015 .

[42]  Frederick E. Ziegler,et al.  The stereocontrolled photoaddition of allene to cyclopent-1-ene-1-carboxaldehydes. A total synthesis of (±) steviol methyl ester and isosteviol methyl ester , 1977 .

[43]  Jianxian Gong,et al.  Total synthesis of (±) maoecrystal V. , 2010, Journal of the American Chemical Society.

[44]  Feng Peng,et al.  Total synthesis of (±)-maoecrystal V. , 2012, Journal of the American Chemical Society.

[45]  H. Hagiwara,et al.  Optically pure (4aS)-(+)- or (4aR)-(-)-1,4a-dimethyl-4,4a,7,8-tetrahydronaphthalene-2,5(3H,6H)-dione and its use in the synthesis of an inhibitor of steroid biosynthesis , 1988 .

[46]  D. Burnell,et al.  GEMINAL ACYLATION OF KETONES MEDIATED BY BORON TRICHLORIDE. AN IMPROVED METHOD FOR THE SYNTHESIS OF 4,4-DIMETHYL-1,3-CYCLOPENTANEDIONES , 1998 .

[47]  S. Masamune.  Total Syntheses of Diterpenes and Diterpene Alkaloids. II.1 A Tetracyclic Common Intermediate , 1964 .