https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

The 3,3'-pyrrolidinyl-spirooxindole unit is a privileged heterocyclic motif that forms the core of a large family of alkaloid natural products with strong bioactivity profiles and interesting structural properties. Significant recent advances in the synthesis of this fused heterocyclic system have led to intense interest in the development of related compounds as potential medicinal agents or biological probes.

Pyrrolidinyl-spirooxindole natural products as inspirations for the development of potential therapeutic agents.

https://chemistry.mdma.ch/hiveboard/rhodium/pdf/archive/merbst/quinoline1999.pdf

Quinoline, quinazoline and acridone alkaloids

As the largest class of natural products, terpenes have a variety of roles in mediating antagonistic and beneficial interactions among organisms. They defend many species of plants, animals and microorganisms against predators, pathogens and competitors, and they are involved in conveying messages to conspecifics and mutualists regarding the presence of food, mates and enemies. Despite the diversity of terpenes known, it is striking how phylogenetically distant organisms have come to use similar structures for common purposes. New natural roles undoubtedly remain to be discovered for this large class of compounds, given that such a small percentage of terpenes has been investigated so far.

The function of terpene natural products in the natural world.

The substituted indole nucleus [indole is the acronym from indigo (the natural dye) and oleum (used for the isolation)] is a structural component of a vast number of biologically active natural and unnatural compounds. The synthesis and functionalization of indoles has been the object of research for over 100 years, and a variety of well-established classical methods are now available, to name a few of them, the Fisher indole synthesis, the Gassman synthesis of indoles from N-halo-anilines, the Madelung cyclization of N-acyl-o-toluidines, the Bischler indole synthesis, the Batcho-Leimgruber synthesis of indoles from o-nitrotoluenes and dimethylformamide acetals, and the reductive cyclization of o-nitrobenzyl ketones.1 In the last 40 years or so, however, palladiumcatalyzed reactions, generally tolerant of a wide range of functionalities and therefore applicable to complex molecules, have achieved an important place in the arsenal of the practicing organic chemist. Since the invention of an industrial process for the palladium-catalyzed production of acetaldehyde from ethylene in the presence of PdCl2 and CuCl2, an everincreasing number of organic transformations have been based on palladium catalysis. Almost every area of the organic synthesis has been deeply influenced by the profound potential of this versatile transition metal, modifying the way organic chemists design and realize synthetic processes.2,3 Because of its catalytic nature, palladium-catalyzed synthesis can provide access to fine chemicals, agrochemical and pharmaceutical intermediates, and active ingredients in fewer steps and with less waste than classical † In memory of Prof. Bianca Rosa Pietroni, a colleague and very close friend. * To whom correspondence should be addressed. Phone: + 39 (06) 4991-2785. Fax: + 30 (06) 4991-2780. E-mail: sandro.cacchi@ uniroma1.it. 2873 Chem. Rev. 2005, 105, 2873−2920

Synthesis and functionalization of indoles through palladium-catalyzed reactions

Jaspines A and B: two new cytotoxic sphingosine derivatives from the marine sponge Jaspis sp.

Microtubules are centrally involved in cell division, being the principal components of mitotic spindle. Tubulin, the constituent of microtubules, can be cyclically modified on its alpha-subunit by enzymatic removal of the COOH-terminal tyrosine residue by an ill-defined tubulin carboxypeptidase (TCP) and its readdition by tubulin tyrosine ligase (TTL). We and others have previously shown that suppression of TTL and resulting accumulation of detyrosinated tubulin are frequent in human cancers of poor prognosis. Explanations for the involvement of TTL and detyrosinated tubulin in tumor progression arise from the recent discovery that tubulin detyrosination leads to CAP-Gly protein mislocalization, which correlates with defects in spindle positioning during mitosis. Impaired control of spindle positioning is one factor favoring tumor invasiveness. Thus, TCP could be a target for developing novel therapeutic strategies against advanced stages of cancers. Inhibitors of TCP, by reversing abnormal detyrosinated tubulin accumulation in tumor cells, could impair tumor progression. TCP has never been isolated and this has hampered search of specific inhibitors. In this article, we describe a cell-based assay of TCP activity and its use to screen a library of natural extracts for their inhibitory potency. This led to the isolation of two sesquiterpene lactones. We subsequently found that parthenolide, a structurally related compound, can efficiently inhibit TCP. This inhibitory activity is a new specific property of parthenolide independent of its action on the nuclear factor-kappaB pathway. Parthenolide is also known for its anticancer properties. Thus, TCP inhibition could be one of the underlying mechanisms of these anticancer properties.

/pdf/parthenolide-inhibits-tubulin-carboxypeptidase-activity-13qygef9x8.pdf

Parthenolide Inhibits Tubulin Carboxypeptidase Activity

New synthetic reactions. A chemoselective approach to cleavage .alpha. to a carbonyl group via .beta.-keto sulfides. Preparation of 1,2-diketones

Alkaloids of Alstonia angustifolia

The haemolytic activity of 59 samples, natural or partially synthetic pure saponins and mixtures thereof, was determined. The tested saponins possessed triterpenic genins and six structural skeleton types were studied. Structure-activity relationships were established by comparison of the functional groups of each saponin and of the branched sugar chains attached to aglycone. The haemolytic activity is shown to depend on the number of sugar units in the chains, as well as on the presence of an osidic chain in position 3 or of functional groups on the genin such as carboxylic or 16a-OH. Comparison of activities of monodesmosidic and bidesmosidic saponins showed that monodesmosidic saponins were generally more active and suggested a polar balance between the two sugar chains at positions 3 and 28. Twelve saponins showed strong haemolytic activity and five possessed a Haemolytic Index (HI) greater than 100,000, such as the a- and s-aescines (HI: 200,000).

/pdf/structure-activity-relationships-of-haemolytic-saponins-28mqd9mebj.pdf

Georges Massiot

Papers

Jaspines A and B: two new cytotoxic sphingosine derivatives from the marine sponge Jaspis sp.

Parthenolide Inhibits Tubulin Carboxypeptidase Activity

New synthetic reactions. A chemoselective approach to cleavage .alpha. to a carbonyl group via .beta.-keto sulfides. Preparation of 1,2-diketones

Alkaloids of Alstonia angustifolia

Structure-Activity Relationships of Haemolytic Saponins