Synthesis and Biological Evaluation of a Novel Acronycine/Duocarmycin Hybrid Natural Product

Abstract

Experimental procedures ______________________________________________________ 3 NMR spectra of rac-3 ________________________________________________________ 8 Biological Test 10 General methods Experimental methods: All air-sensitive reactions were performed under an argon atmosphere in flame-dried flasks and the reactants were introduced by syringe or transfer cannula. All solvents were dried by standard methods and the reagents obtained from commercial sources were used without further purification. Thin-layer chromatography was performed on precoated silica gel plates (TLC silica gel 60 F254, Merck). Silica gel 60 (0.032-0.064 mm, Merck) was used for column chromatography. Flash column chromatography was performed using the Isolera™ One flash purification system by Biotage with pre-packed silica cartridges (SNAP 10, 25, 50, 100 g). NMR spectroscopy: NMR spectra were recorded with a Varian Mercury-300, Unity-300, Inova-500 and Inova-600 spectrometer and a Bruker AMX-300 spectrometer in CDCl 3 ; chemical shifts are given in ppm relative to tetramethylsilane (TMS), coupling constants J in Hertz. The solvent signals were used as references and the chemical shifts converted to the TMS scale (CHCl 3 : δH = 7.24 ppm, δC = 77.36 ppm). The multiplicities of first order were assigned as: s (singlet), d (doublet), t (triplet), q (quartet), dd (doublet of doublets), etc. Signals of higher orders were assigned as m (multiplet). IR spectroscopy: IR spectra were recorded with a JASCO FT/IR-4100 spectrometer. All substances were applied neat on an ATR unit. UV spectroscopy: UV spectra were recorded with a JASCO V-630 spectrometer.