Cysteine Thiol Probe (Probe 1) reacts much more readily with β-lactam- and β-lactone-based electrophilic natural products, and its reactivity with epoxide-based electrophilic natural products is poor. And probe 2 reacts much faster with epoxide-containing natural products. This orthogonal reactivity allows them to be employed in extracts simultaneously. Since Cysteine Thiol Probe is brominated and probe 2 is chlorinated, the isotopic patterns of labeled natural products point toward their structural origin. Competition experiments using Cysteine Thiol Probe and 2 indicated that brominated Cysteine Thiol Probe reacted exclusively with the β-lactam in penicillin G and the β-lactone in salinosporamide A while chlorinated probe 2 alone reacted with the epoxide in salinamide A.