Fig. 4.

Structural diversification. a Diversification of iminium ethers for A-ring and D-ring iminium ether intermediates. Green text highlights the azide component and red text highlights the nucleophile component; positions a and b (in red) mark the sites of particular transformations. Yields refer to isolated yields of products after chromatography on silica. b Stereoconvergence and synthesis of parent NH lactams. Yields refer to isolated yields of products after chromatography on silica. ^aNa₂S, THF or DMF, 65 °C. ^bNaBH₄, MeOH, rt. ^cC9 was also obtained following LAH reduction of C2 (51%). ^dHydrogenation using 10% Pd/C, EtOH. ^eNaN₃, DMF, 70 °C. ^fInversion of stereochemistry. ^g4-Methylbenzenethiol, DMF, 75 °C. ^hD9 was also obtained following LAH reduction of D2 (58%). ⁱNaBD₄, MeOH, rt. ^jStock solutions of sodium thiophenoxides, DMF, 75 °C. ^kSubstituted acetylene, CuSO₄•5H₂O, sodium L-ascorbate, ^tBuOH/H₂O. ^lHydrogenation using 10% Pd/C, AcOH, EtOH. ^mRemoval of non-benzylic side chain via treatment with base. ⁿRemoval of benzylic side chain via dissolving metal reduction. ^oIsolated product is Beck1. See Supplementary Methods for full synthetic details. C and D are 5α-dihydrotestosterone derivatives; E and F are 5β-dihydrotestosterone derivatives; G are trans-androsterone derivatives; I are estrone derivatives. AcOH, acetic acid; PCC, pyridinium chlorochromate; NaH, sodium hydride in 60% mineral oil; Na₂S, sodium sulfide; THF, tetrahydrofuran; DMF, dimethylformamide; NaBH₄, sodium borohydride; MeOH, methanol; EtOH, ethanol, LAH, lithium aluminum hydride in 1 M THF; NaN₃, sodium azide; NaBD₄, sodium borodeuteride; ^tBuOH, tert-butanol; H₂O, distilled water