Hydroxylamine hydrochloride showed initial promise, but it yielded a mixture of desired cyclized product 48 and a partially Boc-deprotected product. After extensive screening on equivalents of hydroxylamine hydrochloride, temperature, additives (NaHCO3, pyridine, TEA, AcOH, PPTS, PTSA), and solvent, a single equivalent of hydroxylamine•HCl in DCM/MeOH (1:1) at 0ºC to ambient temperature followed by addition of an equal volume of saturated NaHCO3 cleanly delivered 48 in 83% yield. This tandem deprotection and double cyclization proved essential to mask the sensitive guanidine and N-hydroxy functional groups. Next, the pivotal C-H amination step utilized to access 1 (35 to 38, Scheme 1C) could be enlisted to smoothly convert 48 to 49 in 76% yield. In a similar fashion to the synthesis of 1, intermediate 49 was deprotected (BCl3 then HCl, 85% yield) and selectively carbamylated (CSI, HCO2H) to deliver 4 in 55% isolated yield after HPLC purification and found to be spectroscopically identical to that reported for the natural product.