Syntheses of Batzelline A, Batzeline B, Isobatzelline A, and Isobatzelline B

Abstract

Batzellines A and B (1a, b) and isobatzellines A and B (2a, b) are 1,3,4,5‐tetrahydropyrrolo[4,3,2‐de]quinoline‐containing marine alkaloids characterized by the presence of a methylthio substituent at C‐2 of the tricyclic system. We describe here the total synthesis of these natural compounds following the synthetic strategy that we have used previously for the synthesis of damirones A and B, batzelline C, isobatzelline C, discorhabdin C, and makaluvamines A, B, C, and D. The introduction of the methylthio group by electrophilic substitution of a pyrrolo[4,3,2‐de]quinoline, appropriately substituted and in a suitable oxidation state, is the key step in the success of these syntheses.

Divergent Total Syntheses of Isobatzellines A/B and Batzelline A

“…5−7 However, synthetic routes to isobatzellines A (1) and B (2) and batzellines A (4) and B (5) bearing the C2-methylthio group have not been fully explored, and their total syntheses have only been reported by Joule's group. 8,9 As part of our ongoing interest in the total synthesis of pyrroloquinoline alkaloids, 5d,10 we herein report efficient and divergent total syntheses of 1, 2, and 4 featuring three key processes, including the ring expansion of benzocyclobutenone oxime sulfonate with NaSMe to construct 2-methylthioindole, 11 a benzyne-mediated cyclization/functionalization cascade to form the tetrahydroquinoline ring, 12 and a Mn-reagent-dependent oxidative formation of iminoquinone and o-benzoquinone.…”

Antineoplastic Agents 491.1 Synthetic Conversion of Aaptamine to Isoaaptamine, 9-Demethylaaptamine, and 4-Methylaaptamine

“…Several methods are known for O-demethylation of isoquinoline derivatives. For example, Alvarez used boron tribromide in dichloromethane as part of a synthesis of batzelline B and Pelletier employed hydrobromic acid for the selective O-demethylation of 6,7-dimethoxy-3,4-dihydroisoquinoline . Because of the limited solubility of aaptamine ( 1 ) in dichloromethane, we used the latter method in a number of experiments under modified conditions.…”

A Divergent Synthesis of Numerous Pyrroloiminoquinone Alkaloids Identifies Promising Antiprotozoal Agents

“…We accessed makaluvamine I (4) and D (44) from the TFA salt of 33 via aminolysis with NH 4 Cl and tyramine as amine sources, respectively. 35,49,63 The inclusion of sat. aq.…”