Wenjun Zhang, 1 Jixun Zhan 1 , Burkhardt I. Wilke, 2 Christopher N. Boddy, 2 * Yi Tang 1 *

1. An alternate route to phenanthrene and isocoumarin lactones containing polyketides via an amide starter unit Wenjun Zhang,1 Jixun Zhan1, Burkhardt I. Wilke,2Christopher N. Boddy,2* Yi Tang1* 1Deparment of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, CA 90095-1592 2Department of Chemistry, Syracuse University, Syracuse, NY 13244-4100 Initiation in aromatic polyketide biosynthesis can occur in one of two ways. Mechanistic rational for spontaneous cyclization of observed products. Synthesis of model bicyclic intermediate shows that amide can act as latent electrophile generating phenanthrone lactones Alkaloid product is possible via alternative mechanism. Synthesis of lactam. Malonamyl starter units can make alkaloids. Mechanisms for KS priming in type II polyketide biosynthesis. (a) Pd(PPh3)4, Me6Sn2, 50 %; (b) Pd(PPh3)4, CuBr, 66 %; (c) NaClO2, 2-methyl-2-butene, 98 %; (d) Zn/AcOH, 87 %; (e) BBr3; 1:1 MeCH/H2O, quant. (a) Pd(PPh3)4, K2CO3, 80 C, 62 %; (b) NaClO2, 2-methyl-2-butene, 87 %; (c) Et3N, MeI, 0C → RT, 83 %; (d) BuLi, NH3(l), THF, -78 C, 98 %; (e) Raney-Ni , 50 % THF/H2O, quant.; (f) BBr3; 1:1 MeCH/H2O, quant Possible products from engineered OxyD systems. Synthesis of coumarin precursor also shows amide is a latent electrophile. • Acknowledgements • Chris Boddy • Tang Lab • Boddy Lab • Coffee (a) BnBr, K2CO3, 100 %; (b) AllylMgBr, 78 %; (c) TBSCl, imid., 89 %; (d) RuCl3, NaIO4; then EDC, NH4Cl, Et3N, 35 %; (e) TsOH, EtOH, 94 %; (f) IBX, 84 %; (g) H2, Pd/C, Pry.; then EtOH, H2O AcOH, 36 % hydroxyamide, 44 % lactone.