1: (2E,4E)-4-Methylhexa-2,4-dienylphosphonic acid diethylester With lithium diisopropyl amide in tetrahydrofuran; hexane T=-78°C; Metallation; 15 h; 2: (2R,3S,4S,5S)-7-[8-hydroxy-5,7-dimethoxy-3-methyl-4-oxo-4H-2-chromenyl]-2,4-dimethoxy-3,5-dimethylheptanal in tetrahydrofuran; hexane T=-78 - 20°C; Condensation; Horner-Wadsworth-Emmons reaction;

1.1: 98 percent / DIPEA / CH2Cl2 / 20 °C 2.1: 240 mg / DMAP / CH2Cl2 / 3 h / 20 °C 3.1: 75 percent / NaOMe / methanol / 2 h / Heating 4.1: 74 percent / H2 / 10 percent Pd/C / methanol / 0.07 h 5.1: oxalyl chloride; DMSO; DIPEA / CH2Cl2 / -78 - 20 °C 6.1: aq. HCl / CH2Cl2 / 0.5 h 7.1: LDA / tetrahydrofuran; hexane / 15 h / -78 °C 7.2: 77 percent / tetrahydrofuran; hexane / -78 - 20 °C View Scheme

1.1: 73 percent / P4O10; H3PO4 / 1 h / 70 °C 2.1: 87 percent / TFA; MCPBA / CH2Cl2 / 16 h / 0 - 5 °C 3.1: 99 percent / aq. HCl / methanol / 2 h / Heating 4.1: 98 percent / DIPEA / CH2Cl2 / 20 °C 5.1: 240 mg / DMAP / CH2Cl2 / 3 h / 20 °C 6.1: 75 percent / NaOMe / methanol / 2 h / Heating 7.1: 74 percent / H2 / 10 percent Pd/C / methanol / 0.07 h 8.1: oxalyl chloride; DMSO; DIPEA / CH2Cl2 / -78 - 20 °C 9.1: aq. HCl / CH2Cl2 / 0.5 h 10.1: LDA / tetrahydrofuran; hexane / 15 h / -78 °C 10.2: 77 percent / tetrahydrofuran; hexane / -78 - 20 °C View Scheme

2.1: 32 percent / K2CO3 / dimethylformamide / 72 h / 80 °C 3.1: 100 percent / K2CO3 / dimethylformamide / 3 h / 0 °C 4.1: 97 percent / DIBAH / CH2Cl2 / 3 h / -78 °C 5.1: 76 percent / PCC / CH2Cl2 / 2 h / 20 °C 6.1: 30 percent aq. hydrogen peroxide; phenylselenic acid / CH2Cl2 / 48 h / 20 °C 6.2: KOH / methanol / 0.5 h / 20 °C 7.1: KOH / dimethylsulfoxide / 3 h / 20 °C 8.1: 100 percent / hydrogen / 20 percent Pd(OH)2/C / methanol / 18 h / 20 °C 9.1: 98 percent / pyridine / diethyl ether / 4 h / 20 °C 10.1: AlCl3 / CH2Cl2 / 3 h / 20 °C 10.2: 94 percent / aq. HCl / methanol / 0.5 h / Heating 11.1: 60 percent / Huenig base / CH2Cl2 / 24 h / 20 °C 12.1: 77 percent / aq. K2CO3; n-Bu3NHSO4 / benzene / 20 h / 20 °C 13.1: NaH / dimethylsulfoxide / 3 h / 20 °C 13.2: aq. oxalic acid / 0 °C 13.3: AcOH; conc. HCl / 1.5 h 14.1: (COCl)2; DIPEA; DMSO / CH2Cl2 / 0.5 h / -78 - 20 °C 15.1: HMPA / tetrahydrofuran / 16 h / -85 - 20 °C View Scheme

1.1: 32 percent / K2CO3 / dimethylformamide / 72 h / 80 °C 2.1: 100 percent / K2CO3 / dimethylformamide / 3 h / 0 °C 3.1: 97 percent / DIBAH / CH2Cl2 / 3 h / -78 °C 4.1: 76 percent / PCC / CH2Cl2 / 2 h / 20 °C 5.1: 30 percent aq. hydrogen peroxide; phenylselenic acid / CH2Cl2 / 48 h / 20 °C 5.2: KOH / methanol / 0.5 h / 20 °C 6.1: KOH / dimethylsulfoxide / 3 h / 20 °C 7.1: 100 percent / hydrogen / 20 percent Pd(OH)2/C / methanol / 18 h / 20 °C 8.1: 98 percent / pyridine / diethyl ether / 4 h / 20 °C 9.1: AlCl3 / CH2Cl2 / 3 h / 20 °C 9.2: 94 percent / aq. HCl / methanol / 0.5 h / Heating 10.1: 60 percent / Huenig base / CH2Cl2 / 24 h / 20 °C 11.1: 77 percent / aq. K2CO3; n-Bu3NHSO4 / benzene / 20 h / 20 °C 12.1: NaH / dimethylsulfoxide / 3 h / 20 °C 12.2: aq. oxalic acid / 0 °C 12.3: AcOH; conc. HCl / 1.5 h 13.1: (COCl)2; DIPEA; DMSO / CH2Cl2 / 0.5 h / -78 - 20 °C 14.1: HMPA / tetrahydrofuran / 16 h / -85 - 20 °C View Scheme

1.1: 99 percent / aq. HCl / methanol / 2 h / Heating 2.1: 98 percent / DIPEA / CH2Cl2 / 20 °C 3.1: 240 mg / DMAP / CH2Cl2 / 3 h / 20 °C 4.1: 75 percent / NaOMe / methanol / 2 h / Heating 5.1: 74 percent / H2 / 10 percent Pd/C / methanol / 0.07 h 6.1: oxalyl chloride; DMSO; DIPEA / CH2Cl2 / -78 - 20 °C 7.1: aq. HCl / CH2Cl2 / 0.5 h 8.1: LDA / tetrahydrofuran; hexane / 15 h / -78 °C 8.2: 77 percent / tetrahydrofuran; hexane / -78 - 20 °C View Scheme

1.1: 240 mg / DMAP / CH2Cl2 / 3 h / 20 °C 2.1: 75 percent / NaOMe / methanol / 2 h / Heating 3.1: 74 percent / H2 / 10 percent Pd/C / methanol / 0.07 h 4.1: oxalyl chloride; DMSO; DIPEA / CH2Cl2 / -78 - 20 °C 5.1: aq. HCl / CH2Cl2 / 0.5 h 6.1: LDA / tetrahydrofuran; hexane / 15 h / -78 °C 6.2: 77 percent / tetrahydrofuran; hexane / -78 - 20 °C View Scheme

1.1: 100 percent / PDC / dimethylformamide / 20 °C 2.1: DIPEA / CH2Cl2 / 0.5 h / 20 °C 3.1: 240 mg / DMAP / CH2Cl2 / 3 h / 20 °C 4.1: 75 percent / NaOMe / methanol / 2 h / Heating 5.1: 74 percent / H2 / 10 percent Pd/C / methanol / 0.07 h 6.1: oxalyl chloride; DMSO; DIPEA / CH2Cl2 / -78 - 20 °C 7.1: aq. HCl / CH2Cl2 / 0.5 h 8.1: LDA / tetrahydrofuran; hexane / 15 h / -78 °C 8.2: 77 percent / tetrahydrofuran; hexane / -78 - 20 °C View Scheme

1.1: DIPEA / CH2Cl2 / 0.5 h / 20 °C 2.1: 240 mg / DMAP / CH2Cl2 / 3 h / 20 °C 3.1: 75 percent / NaOMe / methanol / 2 h / Heating 4.1: 74 percent / H2 / 10 percent Pd/C / methanol / 0.07 h 5.1: oxalyl chloride; DMSO; DIPEA / CH2Cl2 / -78 - 20 °C 6.1: aq. HCl / CH2Cl2 / 0.5 h 7.1: LDA / tetrahydrofuran; hexane / 15 h / -78 °C 7.2: 77 percent / tetrahydrofuran; hexane / -78 - 20 °C View Scheme

1.1: 90 percent / CAN; H2O / acetonitrile / 0.1 h / 0 °C 2.1: 100 percent / PDC / dimethylformamide / 20 °C 3.1: DIPEA / CH2Cl2 / 0.5 h / 20 °C 4.1: 240 mg / DMAP / CH2Cl2 / 3 h / 20 °C 5.1: 75 percent / NaOMe / methanol / 2 h / Heating 6.1: 74 percent / H2 / 10 percent Pd/C / methanol / 0.07 h 7.1: oxalyl chloride; DMSO; DIPEA / CH2Cl2 / -78 - 20 °C 8.1: aq. HCl / CH2Cl2 / 0.5 h 9.1: LDA / tetrahydrofuran; hexane / 15 h / -78 °C 9.2: 77 percent / tetrahydrofuran; hexane / -78 - 20 °C View Scheme