The presented route provides an efficient and highly reproducible method to obtain penultimate allyl-protected intermediates of 3-Substituted 5-Amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indoles (amino-CBIs). De-allylation utilizing Grubbs carbene proved challenging as the authors note in the manuscript and gave poor yields of the desired final compounds in my hands. I found a modified approach utilizing catalytic Pd(PPh3)4 with1-2 equivalents of p-TolSO2Na and CSA in DCM as described in DOI:10.1021/jo971194c significantly improved upon the reported conditions generating high yields (>90%) of the desired amino-CBI products within 30 minutes at room temperature.
The end products tended to be poorly soluble and labile to hydrolysis in solution, DMSO stocks should be stored carefully in single use aliquots at -78 C. Care should also be taken during solubilization as they readily decompose under even mild heating. When handled carefully these products are highly potent DNA alkylators with sub-nanomolar activities against many mammalian cells. Poor solubility and general toxicity limit their applications beyond tool compounds.
Overall the chemistry presented in this paper was robust, well-described, and highly reproducible. Everything worked as described outside of the final step which was accurately noted to be challenging and give low yields. Modifying the final deprotection conditions can thus significantly improve the overall yields and ease of synthesis for these compounds.