Alkaloids pyrroloquinoline

Cytotoxic and antifungal pyrroloquinoline alkaloids have been isolated from the Caribbean deep water sponge Batzella sp. Isobatzelline A (166) is considerably more active than the halogen-free isobatzelline B (P-388 leukemia IC50 0.42 and 2.6 pg/ml, Candida albicans IC50 3.1 and 25 pg/ml, respectively) [127]. 

Alkaloids related to pyridoacridines are known also from sponges and tunicates. Discorhabdin C (79), which is the first marine pyrroloquinoline alkaloid, was isolated from the sponge Latmnculia cf. bocagei. More than 20 alkaloids of this class are known at moment (30). Additional examples of this family are batzelline A (80) from a deep-sea sponge of the genus Batzella and wakayin (81) from an ascidian Clavelina sp. 

The pyrroloquinoline alkaloid family of bioactive marine natural products has been assembled by exploiting a biomimetic strategy. In the case of the iV-benzyl derivative of discorhabdin C (281a), for example, the cation 282 that is formed upon electrooxidation of dibromophenol 279 was intercepted intramolecularly to afford 281a in modest 19% yield [70]. Unfortunately, all attempts to remove the benzyl group failed. Consequently, the approach to the natural product was modified to affect debenzylation earlier in the scheme. Electrochemical oxidation of the free amine 280 did lead to discorhabdin C (281b), albeit in a low yield (24%). 

Pyrroloquinoline alkaloids Bazella sp. n-CyHis- CHCI3 -MeOH - H2O (2 7 6 3) n-CyHis-EtOAc CHCI3-MeOH H2O (4 7 4 3) HSCCC... 

In the case of iridoids, they are ring opened to secoiridoids and are incorporated as monoterpenoid part of important groups of alkaloids indole, ipecacuanha, cinchona, pyrroloquinoline alkaloids and related compounds (ref 8 ). 

Two pyrroloquinoline alkaloids, martinelline (49) and martinellic acid (50), have been isolated from an organic extract of root of Martinella iquitosensis A. Sampaio (Bigno-niaceae) by Witherup et al. (part of Merck s research group) as bradykinin receptor antagonists (Figure 10.11) [85]. The optical rotations of natural 49 and 50 were reported as [a]o +9.4 and -8.5, respectively, however the synthetic ( ) 50 showed a considerably larger value with the same sense ([a]o-122.7 [86,87] -164.3 [88]). A compound with the... 

Sun HH, Sakemi S, Burres N, McCarthy P (1990) Isobatzellines A, B, C, and D. Cytotoxic and antifungal pyrroloquinoline alkaloids from the marine sponge Batzella sp. J Org Chem... 

C, the novel pyrroloquinoline alkaloids isolated from the marine sponge Batzella sp. Chem Lett 1785-1786... 

Legentil L, Lesur B, Delfoume E (2006) Aza-analogues of the marine pyrroloquinoline alkaloids wakayin and tsitsikammamines synthesis and topoisomerase inhibition. Bioorg Med Chem Lett 16 427-429... 

The parent compound of the secoiridoids is secologa-nin (see secoiridoids), the most important intermediate in the biogenesis of alkaloids that are not derived from an amino acid. This includes most indole alkaloids, the ipecac, the Cinchona, and the pyrroloquinoline alkaloids as well as simple monoterpene alkaloids The best known biological property of the I. is their bitter taste. However, bitter principles are mostly not used as pure substances, instead alcoholic extracts are preferred to stimulate appetite (increased secretion of gastric juice). Furthermore, bitter substances are used to modify the taste of pharmaceutical products. Some I. exert various effects on the central nervous system as a consequence of their volatility and lipophilicity, e.g., nepetalactone, iridodial, teucrium lactones, and valepotriates. 

The parent compound of the S. is secologanin, a key compound in the biosyntheses of most indole alkaloids, the Cinchona, ipecac, and pyrroloquinoline alkaloids as well as simple monoterpene alkaloids. Over 1000 indole alkaloids are formed from secologanin in vivo - comprising almost a quarter of this large group of natural products. 

Miyanaga A, Janso JE, McDonald L, He M, Liu HB, Barbieri L, et al. Discovery and assembly-line biosynthesis of the Lymphostin Pyrroloquinoline alkaloid family of mTOR inhibitors in Salinispora bacteria. J Am Chem Soc 2011 133 (34) 13311-3. 

Martinelline 136 and martinellic acid 137 are classified as pyrroloquinoline alkaloids. They were isolated from the roots of the tropical plant, Martinella iquitosensis, and show bradykinin receptor antagonistic activity. Hamada and co-workers reported on a synthesis of the chiral marti-nellin core structures 134 and 135 via organocatalytic cascade reaction. Anthranilaldehyde 130 and enal 131 underwent Michael-aldol reaction in the presence of (S)-... 

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