Total synthesis of (+)-porothramycin B

Synthesis of a novel C2/C2′-exo unsaturated pyrrolobenzodiazepine cross-linking agent with remarkable DNA binding affinity and cytotoxicity

“…9,10 However, this had to be abandoned due to the unwanted addition of EtSH across the C4-exo-methylene of intermediates of type 11 during attempted thioacetal formation. Instead, synthesis of 1 was achieved by employing the B-ring cyclisation strategy first reported by Fukuyama and co-workers 11 (Scheme 1). Commercially available trans-4-hydroxy-l-proline 5 was initially N-protected as carbamate 6 in 87% yield.…”

Isolation, chemistry, and biology of pyrrolo[1,4]benzodiazepine natural products

“…This study features a ring-opening/ring-closing cascade of Zincke pyridinium 105, which was obtained from amino ester 102 over three steps. The cascade reaction proceeds upon exposure to methylamine in ethanol at elevated temperatures, which is performed after TBS protection of the primary In the 1990s, Fukuyama et al 168 published an alternative approach toward porothramycins A ( 16) and B (17) (Scheme 8). Following the conversion of L-glutamic acid 107 into its oxazolidin-5-one derivative 108, the free carboxylic acid moiety was reduced and protected by converting it to corresponding dimethyl acetal.…”

“…In the 1990s, Fukuyama et al 168 published an alternative approach toward porothramycins A ( 16 ) and B ( 17 ) (Scheme 8). Following the conversion of l ‐glutamic acid 107 into its oxazolidin‐5‐one derivative 108 , the free carboxylic acid moiety was reduced and protected by converting it to corresponding dimethyl acetal.…”

Pyrrolobenzodiazepines as Sequence Selective DNA Binding Agents

“…Several research groups have designed new PBDs with potential DNA binding affinity. [35][36][37][38][39] A novel method for the oxidation of PBD secondary amine to the corresponding imines is developed in this laboratory 32 . Although PBDs with either a secondary amine or amide functionality at N10-C11 are readily synthesized, the introduction of imine or carbinolamine at this position is problematic due to the reactivity of these functional groups.…”