Total synthesis of makaluvamine A/D, damirone B, batzelline C, makaluvone, and isobatzelline C featuring one-pot benzyne-mediated cyclization–functionalization

Total Synthesis of Mycenarubin A, Sanguinolentaquinone and Mycenaflavin B and their Cytotoxic Activities

“…This synthetic strategy is similar to the proposed biosynthesis of pyrroloquinoline alkaloids . Different methods for closing the piperidine ring have been described , . For instance, the piperidine ring can be constructed by a biomimetic Michael addition and re‐oxidation of the hydroquinone.…”

Construction of <i>N</i>-Heterocycles Fused with a Highly Substituted Benzene Ring by a Benzyne-Mediated Cyclization/Functionalization Cascade Reaction and Its Application to the Total Synthesis of Marine Natural Products

“…23) 3. Application to the Total Synthesis of Pyrrolo[4,3,2de]quinoline Marine Natural Products [24][25][26] A series of pyrrolo[4,3,2-de] quinoline alkaloids such as damirones, 27) batzellines, 28) makaluvamines, 29) makaluvone, 29) and isobatzellines 30) have been isolated from marine sources, and some of these compounds have been demonstrated to possess a broad range of medicinally important activities such as antitumor activity, 29) inhibitory activity against topoisomerase II, 29) antimalarial activity, 31) and inhibitory activity against envelope-mediated cell fusion of human immunodeficiency virus type 1 28) (Fig. 2).…”

“…First, we optimized conditions for the key benzynemediated cyclization of tetrahydroquinoline skeleton and functionalization using 4-iodoindoline derivative 79, which was prepared from 2-bromo-5-methoxyaniline by a five-step sequence. 38) While the condition using Mg(TMP) 2 •2LiBr or Mg(TMP) 2 •2LiCl provided the desired compound 80 in low yield, benzyne-generation using five equivalents of LiTMP and termination of the reaction by protonation, chlorination, or bromination afforded tetrahydropyrrolo[4,3,2-de] quinolines 80-82 in good yields 24,25) (Chart 14).…”

“…A four-step sequence including DDQ oxidation to indole, deprotection of the two protective groups, and oxidation with Fremy's salt 35) provided p-iminoquinone derivatives 87 or 88. After Nmethylation of 87 or 88, the cleavage of the resulting methyl ether by treatment with BBr 3 and concomitant isomerization to o-quinoline furnished batzelline C (69) 24,25) or makaluvone (66), 25) respectively. N-Methylation of 87 and subsequent addition-elimination-type displacement of the methoxy group with ammonia furnished isobatzelline C (75).…”

Atkamine: A New Pyrroloiminoquinone Scaffold from the Cold Water Aleutian Islands Latrunculia Sponge

“…Several total syntheses of this alkaloid class have been developed, including discorhabdin A, 5 makaluvamine D, 6 and other derivatives. 7 Our discovery efforts searching for novel ring systems from the Alaskan marine region prompted us to focus on the cold water Alaska sponge Latrunculia sp. Although new discorhabdin alkaloids were discovered from our previous studies, 8 an assessment of the extracts using LCMS revealed the generation of uniquely different formulas from those previously reported.…”