Mercedes Álvarez

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3-b]indole

Research on natural products containing hexahydropyrrolo[2,3-b]indole (HPI) has dramatically increased during the past few years. Newly discovered natural products with complex structures and important biological activities have recently been isolated and synthesized. This review summarizes the structures, biological activities, and synthetic routes for natural compounds containing HPI, emphasizing the different strategies for assembling this motif. It covers a broad range of molecules, from small alkaloids to complex peptides.

Recent Advances in Lamellarin Alkaloids: Isolation, Synthesis and Activity

Lamellarins are a large family of marine alkaloids with potential anticancer activity that have been isolated from diverse marine organisms, mainly ascidians and sponges. All lamellarins feature a 3,4-diarylpyrrole system. Pentacyclic lamellarins, whose polyheterocyclic system has a pyrrole core, are the most active compounds. Some of these alkaloids are potently cytotoxic to various tumor cell lines. To date, Lam-D and Lam-H have been identified as lead compounds for the inhibition of topoisomerase I and HIV-1 integrase, respectively-nuclear enzymes which are over-expressed in deregulation disorders. Moreover, these compounds have been reported for their efficacy in treatment of multi-drug resistant (MDR) tumors cells without mediated drug efflux, as well as their immunomodulatory activity and selectivity towards melanoma cell lines. This article is an overview of recent literature on lamellarins, encompassing their isolation, recent synthetic strategies for their total synthesis, the preparation of their analogs, studies on their mechanisms of action, and their structure-activity relationships (SAR).

Thiopeptide Antibiotics: Retrospective and Recent Advances

Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from being limited to their innate antibacterial activity, thiopeptides have been found to possess a wide range of biological properties, including anticancer, antiplasmodial, immunosuppressive, etc. In spite of their ribosomal origin, these highly posttranslationally processed peptides have posed a fascinating synthetic challenge, prompting the development of various methodologies and strategies. Regardless of their limited solubility, intensive investigations are bringing thiopeptide derivatives closer to the clinic, where they are likely to show their veritable therapeutic potential.

Marine, nitrogen-containing heterocyclic naturalm products - structures and synthesis of compounds containing indole units

The structures, biological activities, and syntheses of marine natural products containing indole and dihydroindole nuclei are reviewed

Marine, Nitrogen-containing Heterocyclic Natural Products. Structures and Syntheses of Compounds Containing Quinoline and/or Isoqiunoline Units

The structures, biological activities, and syntheses of marine, natural products containing quinoline and/or isoquinoline nuclei are reviewed

Thiopeptide Engineering: A Multidisciplinary Effort towards Future Drugs

The recent development of thiopeptide analogues of antibiotics has allowed some of the limitations inherent to these naturally occurring substances to be overcome. Chemical synthesis, semisynthetic derivatization, and engineering of the biosynthetic pathway have independently led to complementary modifications of various thiopeptides. Some of the new substances have displayed improved profiles, not only as antibiotics, but also as antiplasmodial and anticancer drugs. The design of novel molecules based on the thiopeptide scaffold appears to be the only strategy to exploit the high potential they have shown in vitro. Herein we present the most relevant achievements in the production of thiopeptide analogues and also discuss the way the different approaches might be combined in a multidisciplinary strategy to produce more sophisticated structures.

Synthesis of deoxyvariolin B

Abstract A synthesis of deoxyvariolin B ( 5 ) is described. The tricyclic pyridopyrrolopyrimidone ( 11 ) was prepared from 7-azaindole via lithiation at C-2, introduction of an aminoethyl side-chain, then closure of the third ring. A heteroaryl palladium(0)-catalysed coupling reaction was used to introduce a pyrimidine substituent at C-5.

Progress on lamellarins

This review covers recent literature on the lamellarins, a family of marine natural products, and related analogs, encompassing synthetic strategies for total synthesis, structure–activity relationships (SAR), and studies on mechanisms of biological action, namely in the context of anti-tumor activity. It reviews work published from January 2008 to December 2010.

Total Synthesis and Antiproliferative Activity Screening of (()-Aplicyanins A, B and E and Related Analogues †

The first total synthesis of the indole alkaloids (+/-)-aplicyanins A, B, and E, plus 17 analogues, all in racemic form, is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the nature of the substituents on the indole nitrogen (H, Me, or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and 14 of the newly synthesized compounds showed considerable cytotoxicity. The assay results were used to establish structure-activity relationships. These results suggest that the presence of the bromine at position 5 of the indole is critical to activity, as well as the acetyl group on the imine nitrogen does in some compounds.

Synthesis of Ascididemine and an Isomer

Ascididemine (9H-quino[4,3,2-de][1,10]phenanthrolin-9-one) (1) and an isomer (9H-quino[4,3,2-de][1,7]phenanthrolin-9-one) (4) have been synthesized starting from 1,4-dimethoxyacridone (7). The acridone was converted into 1,4-dimethoxy-9-ethynylacridine (11) by a triflate coupling. The ethynylacridine was converted in one-pot into 3H-6-methoxypyrido[2,3,4-kl]acridine (15) by reaction with sodium diformylamide; the mechanism of this key transformation is discussed. Conversion into 6H-4-bromopyrido[2,3,4-kl]acridin-6-one (19) and 6H-pyrido[2,3,4-kl]acridin-6-one (17), followed by reaction of each of these under high pressure conditions with acrolein N,N-dimethylhydrazone, gave ascididemine and its isomer, respectively.