Scheme 4. Synthesis of oCOm-21 and -23. Reagents and conditions: (a) BocNH(CH2)2NH2, THF, H2O, 0 °C to rt, 24 (58%); BocNH(CH2)2NBoc(CH2)2NH2, THF, H2O, 0 °C to rt, 25 (mixture with ethyl carbamate). (b) Br2, CCl4, reflux. (c) NEt3, THF, 0 °C, 26 (73% over two steps), 27 (25% over two steps + 1 : 1 inseparable mixture of 27 and ethyl carbamate). (d) PhCH3, 15, reflux, 28 (84% 2.5 : 1 endo : exo), 29 (60% endo) (e) DBU, THF, rt, 30 (61%), 31 (76)%. (f) and (g) 6 M HCl, 1,4-dioxane, 0 °C to rt, oCOM-21 (63%), oCOM-23 (63%). (h) 6 M HCl, 1,4-dioxane, 0 °C to rt (78%). (i) 6 M HCl, 1,4-dioxane, rt to 50 °C (82%). aPurified by reverse phase C-18 solid phase extraction cartridge using 1% aqueous TFA and acetonitrile.
