Synthesis. Key steps in the synthesis involve a temperature sequential separation of diastereomers as well as a copper-catalysed intramolecular Buchner reaction 33 to construct the key hydrocarbon framework. Conditions: (i) 2.5 equiv. Na, 2.5 equiv. t BuOH, Et 2 O, 21 C, 14 h; (ii) 1.5 equiv. ethyl diazoacetate, 1.0 mol% Rh 2 (OAc) 4 , CH 2 Cl 2 , 21 C, 20 h; (iii) 3.0 equiv. KOH, EtOH, 21 C, 8 h; (iv) 3.0 equiv KOH, EtOH, reflux, 3 h; (v) 1.0 equiv. carbonyldiimidazol, THF, 21 C, 1 h; (vi) 2.5 equiv. AcOMe or AcO t Bu, 5.0 equiv. lithium diisopropyl amide, THF, -78 to 21 C, 3 h; (vii) 1.1 equiv. 4-acetamidobenzenesulfonyl azide, 1.1 equiv. Et 3 N, MeCN, 0 to 21 C, 3 h; (viii) 10 mol% Cu(hFacac) 2 x H 2 O, C 6 H 5 Cl, reflux, 3 h; (ix) 2.0 equiv. DDQ, C 6 H 5 Cl, 130 C, 4 h; (x) 4.0 equiv. KOH, MeOH/H 2 O (1:1), 21 C, 27 h. DDQ, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; hFacac, hexafluoroacetylacetonate.
